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Rheumatoid Arthritis: HELP
Articles from Birmingham, AL
Based on 244 articles published since 2008
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These are the 244 published articles about Arthritis, Rheumatoid that originated from Birmingham, AL during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10
1 Guideline 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. 2017

Goodman, Susan M / Springer, Bryan / Guyatt, Gordon / Abdel, Matthew P / Dasa, Vinod / George, Michael / Gewurz-Singer, Ora / Giles, Jon T / Johnson, Beverly / Lee, Steve / Mandl, Lisa A / Mont, Michael A / Sculco, Peter / Sporer, Scott / Stryker, Louis / Turgunbaev, Marat / Brause, Barry / Chen, Antonia F / Gililland, Jeremy / Goodman, Mark / Hurley-Rosenblatt, Arlene / Kirou, Kyriakos / Losina, Elena / MacKenzie, Ronald / Michaud, Kaleb / Mikuls, Ted / Russell, Linda / Sah, Alexander / Miller, Amy S / Singh, Jasvinder A / Yates, Adolph. ·Susan M. Goodman, MD, Lisa A. Mandl, MD, MPH, Peter Sculco, MD, Barry Brause, MD, Kyriakos Kirou, MD, Ronald MacKenzie, MD, Linda Russell, MD: Hospital for Special Surgery/Weill Cornell Medicine, New York, New York. Electronic address: goodmans@hss.edu. · Bryan Springer, MD: OrthoCarolina Hip and Knee Center, Charlotte, North Carolina. · Gordon Guyatt, MD: McMaster University, Hamilton, Ontario, Canada. · Matthew P. Abdel, MD: Mayo Clinic, Rochester, Minnesota. · Vinod Dasa, MD: Louisiana State University, New Orleans. · Michael George, MD: University of Pennsylvania, Philadelphia. · Ora Gewurz-Singer, MD: University of Michigan, Ann Arbor. · Jon T. Giles, MD, MPH: Columbia University, New York, New York. · Beverly Johnson, MD: Albert Einstein College of Medicine, Bronx, New York. · Steve Lee, DO: Kaiser Permanente, Fontana, California. · Susan M. Goodman, MD, Lisa A. Mandl, MD, MPH, Peter Sculco, MD, Barry Brause, MD, Kyriakos Kirou, MD, Ronald MacKenzie, MD, Linda Russell, MD: Hospital for Special Surgery/Weill Cornell Medicine, New York, New York. · Michael A. Mont, MD: Cleveland Clinic, Cleveland, Ohio. · Scott Sporer, MD: Midwest Orthopaedics at Rush, Chicago, Illinois. · Louis Stryker, MD: University of Texas Medical Branch, Galveston. · Marat Turgunbaev, MD, MPH, Amy S. Miller: American College of Rheumatology, Atlanta, Georgia. · Antonia F. Chen, MD, MBA: Rothman Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. · Jeremy Gililland, MD: University of Utah, Salt Lake City. · Mark Goodman, MD, Adolph Yates, MD: University of Pittsburgh, Pittsburgh, Pennsylvania. · Arlene Hurley-Rosenblatt, ANP: Rockefeller University, New York, New York. · Elena Losina, PhD: Brigham and Women's Hospital, Boston, Massachusetts. · Kaleb Michaud, PhD: National Data Bank for Rheumatic Diseases, Wichita, Kansas and University of Nebraska Medical Center, Omaha. · Ted Mikuls, MD, MSPH: University of Nebraska Medical Center, Omaha. · Alexander Sah, MD: Dearborn-Sah Institute for Joint Restoration, Fremont, California. · Jasvinder A. Singh, MBBS, MPH: University of Alabama at Birmingham. ·J Arthroplasty · Pubmed #28629905.

ABSTRACT: OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

2 Guideline 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. 2017

Goodman, Susan M / Springer, Bryan / Guyatt, Gordon / Abdel, Matthew P / Dasa, Vinod / George, Michael / Gewurz-Singer, Ora / Giles, Jon T / Johnson, Beverly / Lee, Steve / Mandl, Lisa A / Mont, Michael A / Sculco, Peter / Sporer, Scott / Stryker, Louis / Turgunbaev, Marat / Brause, Barry / Chen, Antonia F / Gililland, Jeremy / Goodman, Mark / Hurley-Rosenblatt, Arlene / Kirou, Kyriakos / Losina, Elena / MacKenzie, Ronald / Michaud, Kaleb / Mikuls, Ted / Russell, Linda / Sah, Alexander / Miller, Amy S / Singh, Jasvinder A / Yates, Adolph. ·Hospital for Special Surgery/Weill Cornell Medicine, New York, New York. · OrthoCarolina Hip and Knee Center, Charlotte, North Carolina. · McMaster University, Hamilton, Ontario, Canada. · Mayo Clinic, Rochester, Minnesota. · Louisiana State University, New Orleans. · University of Pennsylvania, Philadelphia. · University of Michigan, Ann Arbor. · Columbia University, New York, New York. · Albert Einstein College of Medicine, Bronx, New York. · Kaiser Permanente, Fontana, California. · Cleveland Clinic, Cleveland, Ohio. · Midwest Orthopaedics at Rush, Chicago, Illinois. · University of Texas Medical Branch, Galveston. · American College of Rheumatology, Atlanta, Georgia. · Rothman Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. · University of Utah, Salt Lake City. · University of Pittsburgh, Pittsburgh, Pennsylvania. · Rockefeller University, New York, New York. · Brigham and Women's Hospital, Boston, Massachusetts. · National Data Bank for Rheumatic Diseases, Wichita, Kansas, and University of Nebraska Medical Center, Omaha. · University of Nebraska Medical Center, Omaha. · Dearborn-Sah Institute for Joint Restoration, Fremont, California. · University of Alabama at Birmingham. ·Arthritis Rheumatol · Pubmed #28620948.

ABSTRACT: OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

3 Guideline 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. 2016

Singh, Jasvinder A / Saag, Kenneth G / Bridges, S Louis / Akl, Elie A / Bannuru, Raveendhara R / Sullivan, Matthew C / Vaysbrot, Elizaveta / McNaughton, Christine / Osani, Mikala / Shmerling, Robert H / Curtis, Jeffrey R / Furst, Daniel E / Parks, Deborah / Kavanaugh, Arthur / O'Dell, James / King, Charles / Leong, Amye / Matteson, Eric L / Schousboe, John T / Drevlow, Barbara / Ginsberg, Seth / Grober, James / St Clair, E William / Tindall, Elizabeth / Miller, Amy S / McAlindon, Timothy. ·University of Alabama at Birmingham. · American University of Beirut, Beirut, Lebanon, and McMaster University, Hamilton, Ontario, Canada. · Tufts Medical Center, Boston, Massachusetts. · Beth Israel Deaconess Medical Center, Boston, Massachusetts. · University of California, Los Angeles. · Washington University School of Medicine, St. Louis, Missouri. · University of California, San Diego. · University of Nebraska Medical Center, Omaha. · North Mississippi Medical Center, Tupelo. · Healthy Motivation, Santa Barbara, California. · Mayo Clinic, Rochester, Minnesota. · University of Minnesota and Park Nicollet Clinic, St. Louis Park. · NorthShore University Health System, Evanston, Illinois. · Global Healthy Living Foundation, New York, New York. · Duke University Medical Center, Durham, North Carolina. · Rheumatology Consultants of Oregon, West Linn. · American College of Rheumatology, Atlanta, Georgia. ·Arthritis Rheumatol · Pubmed #26545940.

ABSTRACT: OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

4 Guideline 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. 2016

Singh, Jasvinder A / Saag, Kenneth G / Bridges, S Louis / Akl, Elie A / Bannuru, Raveendhara R / Sullivan, Matthew C / Vaysbrot, Elizaveta / McNaughton, Christine / Osani, Mikala / Shmerling, Robert H / Curtis, Jeffrey R / Furst, Daniel E / Parks, Deborah / Kavanaugh, Arthur / O'Dell, James / King, Charles / Leong, Amye / Matteson, Eric L / Schousboe, John T / Drevlow, Barbara / Ginsberg, Seth / Grober, James / St Clair, E William / Tindall, Elizabeth / Miller, Amy S / McAlindon, Timothy / Anonymous1780848. ·University of Alabama at Birmingham. · American University of Beirut, Beirut, Lebanon, and McMaster University, Hamilton, Ontario, Canada. · Tufts Medical Center, Boston, Massachusetts. · Beth Israel Deaconess Medical Center, Boston, Massachusetts. · University of California, Los Angeles. · Washington University School of Medicine, St. Louis, Missouri. · University of California, San Diego. · University of Nebraska Medical Center, Omaha. · North Mississippi Medical Center, Tupelo. · Healthy Motivation, Santa Barbara, California. · Mayo Clinic, Rochester, Minnesota. · University of Minnesota and Park Nicollet Clinic, St. Louis Park. · NorthShore University Health System, Evanston, Illinois. · Global Healthy Living Foundation, New York, New York. · Duke University Medical Center, Durham, North Carolina. · Rheumatology Consultants of Oregon, West Linn. · American College of Rheumatology, Atlanta, Georgia. ·Arthritis Care Res (Hoboken) · Pubmed #26545825.

ABSTRACT: OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

5 Editorial Pneumocystis and glucocorticoid use: to prophylax or not to prophylax (and when?); that is the question. 2018

Winthrop, Kevin L / Baddley, John W. ·Division of Infectious Diseases, Oregon Health and Sciences University, Portland, Oregon, USA. · Division of Infectious Diseases, University of Alabama, Birmingham, Alabama, USA. ·Ann Rheum Dis · Pubmed #29459427.

ABSTRACT: -- No abstract --

6 Editorial Gout: will the "King of Diseases" be the first rheumatic disease to be cured? 2016

Singh, Jasvinder A. ·Birmingham VA Medical Center, Birmingham, AL, USA. jasvinder.md@gmail.com. · Department of Medicine at the School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. jasvinder.md@gmail.com. · Division of Epidemiology at the School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA. jasvinder.md@gmail.com. ·BMC Med · Pubmed #27832792.

ABSTRACT: Gout is the most common inflammatory arthritis in adults in the Western world. Characterized by hyperuricemia and the effects of acute and chronic inflammation in joints and bursa, gout leads to an agonizing, chronically painful arthritis. Arthritis can also be accompanied by urate nephropathy and subcutaneous urate deposits (tophi). Exciting new developments in the last decade have brought back the focus on this interesting, crystal-induced chronic inflammatory condition. New insights include the role of NALP3 inflammasome-induced inflammation in acute gout, the characterization of diagnostic signs on ultrasound and dual-energy computed tomography imaging modalities, the recognition of target serum urate less than 6 mg/day as the goal for urate-lowering therapies, and evidence-based treatment guidelines. A better understanding of disease mechanisms has enabled drug discovery - three new urate-lowering drugs have been approved in the last decade, with several more in the pipeline. We now recognize the important role that environment and genetics play in the causation of gout. A focus on the cardiac, renal, and metabolic comorbidities of gout will help translational research and discovery over the next decade.

7 Editorial Cervical cancer risk with the use of tumour necrosis factor inhibitors in rheumatoid arthritis: to worry or not to worry? 2016

Singh, Jasvinder A. ·Medicine Service, Birmingham VA Medical Center, Birmingham, Alabama, USA Department of Medicine at School of Medicine, Division of Epidemiology at School of Public Health, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. ·Ann Rheum Dis · Pubmed #26951640.

ABSTRACT: -- No abstract --

8 Editorial Do "Evidence-Based Recommendations" Need to Reveal the Evidence? Minimal Criteria Supporting an "Evidence Claim". 2015

Christensen, Robin / Singh, Jasvinder A / Wells, George A / Tugwell, Peter S. ·Musculoskeletal Statistics Unit, The Parker Institute, Department of Rheumatology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; robin.christensen@regionh.dk. · Medicine Service, Birmingham VA Medical Center, Department of Medicine at School of Medicine, and Division of Epidemiology at School of Public Health, University of Alabama, Birmingham, AL; and Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA; · University of Ottawa Heart Institute, Ottawa, Canada; · School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada. ·J Rheumatol · Pubmed #26429204.

ABSTRACT: -- No abstract --

9 Editorial Editorial: Arthroplasty outcomes are improving, but why isn't my patient with rheumatoid arthritis doing as well? 2014

Singh, Jasvinder A. ·Birmingham VA Medical Center and University of Alabama at, Birmingham; Mayo Clinic, Rochester, Minnesota. ·Arthritis Rheumatol · Pubmed #24504796.

ABSTRACT: -- No abstract --

10 Editorial Folic acid supplementation for rheumatoid arthritis patients on methotrexate: the good gets better. 2013

Singh, Jasvinder A. ·Medicine Service, Birmingham VA Medical Center, Birmingham, AL. ·Cochrane Database Syst Rev · Pubmed #24151647.

ABSTRACT: -- No abstract --

11 Editorial Ethnic-specific genetic analyses in rheumatoid arthritis: incremental gains but valuable contributions to the big picture. 2013

Danila, Maria I / Reynolds, Richard J / Tiwari, Hemant K / Bridges, S Louis. ·University of Alabama at, Birmingham. ·Arthritis Rheum · Pubmed #23918636.

ABSTRACT: -- No abstract --

12 Editorial Tumor necrosis factor, tuberculosis, testing, and treatment: teeing up the questions. 2013

Saag, Kenneth G / Winthrop, Kevin / Curtis, Jeffrey R. ·University of Alabama at, Birmingham. ·Arthritis Care Res (Hoboken) · Pubmed #23836500.

ABSTRACT: -- No abstract --

13 Review Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients. 2018

Taylor, John C / Bongartz, Tim / Massey, Jonathan / Mifsud, Borbala / Spiliopoulou, Athina / Scott, Ian C / Wang, Jianmei / Morgan, Michael / Plant, Darren / Colombo, Marco / Orchard, Peter / Twigg, Sarah / McInnes, Iain B / Porter, Duncan / Freeston, Jane E / Nam, Jackie L / Cordell, Heather J / Isaacs, John D / Strathdee, Jenna L / Arnett, Donna / de Hair, Maria J H / Tak, Paul P / Aslibekyan, Stella / van Vollenhoven, Ronald F / Padyukov, Leonid / Bridges, S Louis / Pitzalis, Costantino / Cope, Andrew P / Verstappen, Suzanne M M / Emery, Paul / Barnes, Michael R / Agakov, Felix / McKeigue, Paul / Mushiroda, Taisei / Kubo, Michiaki / Weinshilboum, Richard / Barton, Anne / Morgan, Ann W / Barrett, Jennifer H / Anonymous8581104 / Anonymous8591104 / Anonymous8601104. ·Leeds Institute of Cancer and Pathology, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK. · Vanderbilt University, Nashville, TN, USA. · Arthritis Research UK Centre for Genetics and Genomics, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. · NIHR Manchester BRC, Central Manchester Foundation Trust, Manchester, UK. · Clinical Pharmacology, William Harvey Research Institute, Queen Mary University, London, UK. · Centre for Population Health Sciences, Usher Institute, University of Edinburgh Old Medical School, Teviot Place, Edinburgh, UK. · Pharmatics Ltd., 9, Little France Road, Edinburgh, UK. · Research Institute for Primary Care and Health Sciences, Primary Care Sciences, Keele University and Department of Rheumatology, Haywood Hospital, High Lane, Burslem, Staffordshire, UK. · Department of Medical and Molecular Genetics, King's College London, London, UK. · Roche Products, Welwyn Garden City, UK. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK. · Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK. · Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. · Institute of Genetic Medicine, Newcastle University, Newcastle, UK. · Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University and NIHR Newcastle Biomedical Research Centre in Ageing and Long Term Conditions, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. · University of Kentucky College of Public Health, Lexington, KY, 40536, USA. · University Medical Center Utrecht, Utrecht, The Netherlands. · Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · GlaxoSmithKline, Stevenage, UK. · Cambridge University, Cambridge, UK. · Ghent University, Ghent, Belgium. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA. · Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. · Barts and The London School of Medicine & Dentistry, William Harvey Research Institute, Queen Mary University, London, UK. · Academic Department of Rheumatology, Faculty of Life Sciences and Medicine, King's College London, London, UK. · RIKEN Center for Integrative Medical Sciences, Tokyo, Japan. · Mayo Clinic, Rochester, MN, USA. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK. a.w.morgan@leeds.ac.uk. ·Pharmacogenomics J · Pubmed #29795407.

ABSTRACT: Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10

14 Review Unmasking Fucosylation: from Cell Adhesion to Immune System Regulation and Diseases. 2018

Li, Jun / Hsu, Hui-Chen / Mountz, John D / Allen, John G. ·Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. · Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Birmingham VA Medical Center, Birmingham, AL 35294, USA. · Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: johallen@amgen.com. ·Cell Chem Biol · Pubmed #29526711.

ABSTRACT: Fucosylation is a biological process broadly observed in vertebrates, invertebrates, plants, bacteria, and fungi. Fucose moieties on cell-surface glycans are increasingly recognized as critical to many cell-cell interaction and signaling processes. One of the characteristic roles of fucose is its regulation of selectin-dependent leukocyte adhesion that has been well studied over the last two decades. Recent studies of fucose in immune cell development and function regulation have significantly expanded the contemporary understanding of fucosylation. From cellular adhesion to immune regulation, herein we discuss the use of gene knockout studies, competitive inhibitors of fucose-containing glycan, and metabolic inhibitors of fucose biosynthesis to probe fucosylated glycan biosynthesis and signaling and its functional consequences. Promising clinical and preclinical applications in sickle cell disease, rheumatoid arthritis, tumor inhibition, metastasis prevention, antibody-dependent cell-mediated cytotoxicity, chemoresistance reversal, and in improving chemotherapy-related side effects and recovery are reviewed.

15 Review Gastrointestinal Perforations with Biologics in Patients with Rheumatoid Arthritis: Implications for Clinicians. 2018

Jagpal, Aprajita / Curtis, Jeffrey R. ·Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, FOT 802D, Birmingham, AL, 35294, USA. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, FOT 802D, Birmingham, AL, 35294, USA. jcurtis@uab.edu. ·Drug Saf · Pubmed #29392593.

ABSTRACT: Gastrointestinal (GI) perforations are rare events in rheumatoid arthritis (RA) patients, but cause significant morbidity and mortality. Several studies indicate that RA patients may be at higher risk of GI perforation. Traditional RA treatments such as glucocorticoids and non-steroidal anti-inflammatory drugs increase the risk of perforation. In the past two decades, a new class of therapeutic agents called biologics has been added to the RA treatment armamentarium. Biologics are effective in controlling disease activity and are generally well tolerated; however, reports of GI perforations in association with biologics have arisen. In particular, drugs that inhibit the interleukin (IL)-6 cytokine receptor have demonstrated a higher risk of perforation compared with other therapies. Recent reports also suggest that janus kinase inhibitors may increase the risk of perforation, perhaps via downstream effects on IL-6 signaling. In this review, we discuss current data on the risk of GI perforations among RA patients receiving targeted therapies and its clinical relevance.

16 Review Systematic Literature Review and Meta-analysis of Tumor Necrosis Factor-Alpha Experienced Rheumatoid Arthritis. 2017

Wells, Alvin F / Curtis, Jeffrey R / Betts, Keith A / Douglas, Kevin / Du, Ella Xiaoyan / Ganguli, Arijit. ·Rheumatology and Immunotherapy Center, Franklin, Wisconsin. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama. · Analysis Group, Inc, Los Angeles, California. Electronic address: keith.betts@analysisgroup.com. · AbbVie, Inc, North Chicago, Illinois. · Analysis Group, Inc, Los Angeles, California. ·Clin Ther · Pubmed #28734661.

ABSTRACT: PURPOSE: The goal of this study was to compile all available evidence regarding the efficacy of tumor necrosis factor-α (TNF) inhibitors, non-TNF biologics, and tofacitinib for TNF-experienced patients who have rheumatoid arthritis (RA). METHODS: A systematic literature review of MEDLINE, EMBASE, and rheumatology conference abstracts was performed to identify observational studies and randomized controlled trials (RCTs) reporting American College of Rheumatology response rates (ACR 20/50/70) for adult patients with RA who switched from at least 1 TNF to another TNF or a non-TNF therapy. A direct random effects meta-analysis was performed to evaluate ACR 20/50/70 response rates for TNF and non-TNF therapies. Separate analyses were conducted among 3-, 6-, and 12-month observational studies and for 6-month RCTs. FINDINGS: A total of 18 observational studies and 6 RCTs were selected. Among 3-month observational studies, the percentages of ACR20/50/70 responders switching to another TNF were similar to those switching to a non-TNF biologic (ACR20, 54.5% vs 58.6%; ACR50, 33.3% vs 33.3%; and ACR70, 13.0% vs 14.6%, respectively). Among 6-month observational studies, the percentages of TNF ACR20/50/70 responders were higher than those of non-TNF responders (ACR20, 67.7% vs 50.4%; ACR50, 50.4% vs 26.6%; and ACR70, 24.9% vs 11.6%). Among 6-month RCTs, the percentages of non-TNF biologic ACR20/50/70 responders were similar to those in the 6-month non-TNF observational studies (ACR20, 50.7% vs 50.4%; ACR50, 27.5% vs 26.6%; and ACR70, 11.9% vs 11.6%). For 12-month observational studies, TNF biologic ACR20/50/70 percentages were higher than those of non-TNF therapies (ACR20, 72.2% vs 57.0%; ACR50, 42.1% vs 28.9%; and ACR70, 22.9% vs 10.0%). IMPLICATIONS: For TNF-experienced patients with RA, subsequent TNF therapy and non-TNF biologic therapy have comparable efficacy.

17 Review 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. 2017

Goodman, Susan M / Springer, Bryan / Guyatt, Gordon / Abdel, Matthew P / Dasa, Vinod / George, Michael / Gewurz-Singer, Ora / Giles, Jon T / Johnson, Beverly / Lee, Steve / Mandl, Lisa A / Mont, Michael A / Sculco, Peter / Sporer, Scott / Stryker, Louis / Turgunbaev, Marat / Brause, Barry / Chen, Antonia F / Gililland, Jeremy / Goodman, Mark / Hurley-Rosenblatt, Arlene / Kirou, Kyriakos / Losina, Elena / MacKenzie, Ronald / Michaud, Kaleb / Mikuls, Ted / Russell, Linda / Sah, Alexander / Miller, Amy S / Singh, Jasvinder A / Yates, Adolph. ·Hospital for Special Surgery/Weill Cornell Medicine, New York, New York. · OrthoCarolina Hip and Knee Center, Charlotte, North Carolina. · McMaster University, Hamilton, Ontario, Canada. · Mayo Clinic, Rochester, Minnesota. · Louisiana State University, New Orleans. · University of Pennsylvania, Philadelphia. · University of Michigan, Ann Arbor. · Columbia University, New York, New York. · Albert Einstein College of Medicine, Bronx, New York. · Kaiser Permanente, Fontana, California. · Cleveland Clinic, Cleveland, Ohio. · Midwest Orthopaedics at Rush, Chicago, Illinois. · University of Texas Medical Branch, Galveston. · American College of Rheumatology, Atlanta, Georgia. · Rothman Institute, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. · University of Utah, Salt Lake City. · University of Pittsburgh, Pittsburgh, Pennsylvania. · Rockefeller University, New York, New York. · Brigham and Women's Hospital, Boston, Massachusetts. · National Data Bank for Rheumatic Diseases, Wichita, Kansas and University of Nebraska Medical Center, Omaha. · University of Nebraska Medical Center, Omaha. · Dearborn-Sah Institute for Joint Restoration, Fremont, California. · University of Alabama at Birmingham. ·Arthritis Care Res (Hoboken) · Pubmed #28620917.

ABSTRACT: OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

18 Review Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis. 2017

Singh, Jasvinder A / Hossain, Alomgir / Mudano, Amy S / Tanjong Ghogomu, Elizabeth / Suarez-Almazor, Maria E / Buchbinder, Rachelle / Maxwell, Lara J / Tugwell, Peter / Wells, George A. ·Department of Medicine, Birmingham VA Medical Center, Faculty Office Tower 805B, 510 20th Street South, Birmingham, AL, USA, 35294. · Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, 40 Ruskin Street, Room H-2265, Ottawa, ON, Canada, K1Y 4W7. · Department of Medicine - Rheumatology, University of Alabama at Birmingham, Birmingham, USA. · Bruyère Research Institute, University of Ottawa, 43 Bruyère St, Annex E, room 213, Ottawa, ON, Canada, K1N 5C8. · Department of General Internal Medicine, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1465, Houston, Texas, USA, 77030. · Monash Department of Clinical Epidemiology, Cabrini Hospital, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Suite 41, Cabrini Medical Centre, 183 Wattletree Road, Malvern, Victoria, Australia, 3144. · Centre for Practice-Changing Research (CPCR), Ottawa Hospital Research Institute (OHRI), The Ottawa Hospital - General Campus, 501 Smyth Road, Box 711, Ottawa, ON, Canada, K1H 8L6. · Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, K1H 8M5. · Department of Epidemiology and Community Medicine, University of Ottawa, Room H1281, 40 Ruskin Street, Ottawa, ON, Canada, K1Y 4W7. ·Cochrane Database Syst Rev · Pubmed #28481462.

ABSTRACT: BACKGROUND: Biologic disease-modifying anti-rheumatic drugs (biologics) are highly effective in treating rheumatoid arthritis (RA), however there are few head-to-head biologic comparison studies. We performed a systematic review, a standard meta-analysis and a network meta-analysis (NMA) to update the 2009 Cochrane Overview. This review is focused on the adults with RA who are naive to methotrexate (MTX) that is, receiving their first disease-modifying agent. OBJECTIVES: To compare the benefits and harms of biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib versus comparator (methotrexate (MTX)/other DMARDs) in people with RA who are naive to methotrexate. METHODS: In June 2015 we searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE and Embase; and trials registers. We used standard Cochrane methods. We calculated odds ratios (OR) and mean differences (MD) along with 95% confidence intervals (CI) for traditional meta-analyses and 95% credible intervals (CrI) using a Bayesian mixed treatment comparisons approach for network meta-analysis (NMA). We converted OR to risk ratios (RR) for ease of interpretation. We also present results in absolute measures as risk difference (RD) and number needed to treat for an additional beneficial or harmful outcome (NNTB/H). MAIN RESULTS: Nineteen RCTs with 6485 participants met inclusion criteria (including five studies from the original 2009 review), and data were available for four TNF biologics (adalimumab (six studies; 1851 participants), etanercept (three studies; 678 participants), golimumab (one study; 637 participants) and infliximab (seven studies; 1363 participants)) and two non-TNF biologics (abatacept (one study; 509 participants) and rituximab (one study; 748 participants)).Less than 50% of the studies were judged to be at low risk of bias for allocation sequence generation, allocation concealment and blinding, 21% were at low risk for selective reporting, 53% had low risk of bias for attrition and 89% had low risk of bias for major baseline imbalance. Three trials used biologic monotherapy, that is, without MTX. There were no trials with placebo-only comparators and no trials of tofacitinib. Trial duration ranged from 6 to 24 months. Half of the trials contained participants with early RA (less than two years' duration) and the other half included participants with established RA (2 to 10 years). Biologic + MTX versus active comparator (MTX (17 trials (6344 participants)/MTX + methylprednisolone 2 trials (141 participants))In traditional meta-analyses, there was moderate-quality evidence downgraded for inconsistency that biologics with MTX were associated with statistically significant and clinically meaningful benefit versus comparator as demonstrated by ACR50 (American College of Rheumatology scale) and RA remission rates. For ACR50, biologics with MTX showed a risk ratio (RR) of 1.40 (95% CI 1.30 to 1.49), absolute difference of 16% (95% CI 13% to 20%) and NNTB = 7 (95% CI 6 to 8). For RA remission rates, biologics with MTX showed a RR of 1.62 (95% CI 1.33 to 1.98), absolute difference of 15% (95% CI 11% to 19%) and NNTB = 5 (95% CI 6 to 7). Biologics with MTX were also associated with a statistically significant, but not clinically meaningful, benefit in physical function (moderate-quality evidence downgraded for inconsistency), with an improvement of HAQ scores of -0.10 (95% CI -0.16 to -0.04 on a 0 to 3 scale), absolute difference -3.3% (95% CI -5.3% to -1.3%) and NNTB = 4 (95% CI 2 to 15).We did not observe evidence of differences between biologics with MTX compared to MTX for radiographic progression (low-quality evidence, downgraded for imprecision and inconsistency) or serious adverse events (moderate-quality evidence, downgraded for imprecision). Based on low-quality evidence, results were inconclusive for withdrawals due to adverse events (RR of 1.32, but 95% confidence interval included possibility of important harm, 0.89 to 1.97). Results for cancer were also inconclusive (Peto OR 0.71, 95% CI 0.38 to 1.33) and downgraded to low-quality evidence for serious imprecision. Biologic without MTX versus active comparator (MTX 3 trials (866 participants)There was no evidence of statistically significant or clinically important differences for ACR50, HAQ, remission, (moderate-quality evidence for these benefits, downgraded for imprecision), withdrawals due to adverse events,and serious adverse events (low-quality evidence for these harms, downgraded for serious imprecision). All studies were for TNF biologic monotherapy and none for non-TNF biologic monotherapy. Radiographic progression was not measured. AUTHORS' CONCLUSIONS: In MTX-naive RA participants, there was moderate-quality evidence that, compared with MTX alone, biologics with MTX was associated with absolute and relative clinically meaningful benefits in three of the efficacy outcomes (ACR50, HAQ scores, and RA remission rates). A benefit regarding less radiographic progression with biologics with MTX was not evident (low-quality evidence). We found moderate- to low-quality evidence that biologic therapy with MTX was not associated with any higher risk of serious adverse events compared with MTX, but results were inconclusive for withdrawals due to adverse events and cancer to 24 months.TNF biologic monotherapy did not differ statistically significantly or clinically meaningfully from MTX for any of the outcomes (moderate-quality evidence), and no data were available for non-TNF biologic monotherapy.We conclude that biologic with MTX use in MTX-naive populations is beneficial and that there is little/inconclusive evidence of harms. More data are needed for tofacitinib, radiographic progression and harms in this patient population to fully assess comparative efficacy and safety.

19 Review Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis. 2017

Singh, Jasvinder A / Hossain, Alomgir / Tanjong Ghogomu, Elizabeth / Mudano, Amy S / Maxwell, Lara J / Buchbinder, Rachelle / Lopez-Olivo, Maria Angeles / Suarez-Almazor, Maria E / Tugwell, Peter / Wells, George A. ·Department of Medicine, Birmingham VA Medical Center, Faculty Office Tower 805B, 510 20th Street South, Birmingham, AL, USA, 35294. · Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, 40 Ruskin Street, Room H-2265, Ottawa, ON, Canada, K1Y 4W7. · Bruyère Research Institute, University of Ottawa, 43 Bruyère St, Annex E, room 302, Ottawa, ON, Canada, K1N 5C8. · Department of Medicine - Rheumatology, University of Alabama at Birmingham, Birmingham, USA. · Centre for Practice-Changing Research (CPCR), Ottawa Hospital Research Institute (OHRI), The Ottawa Hospital - General Campus, 501 Smyth Road, Box 711, Ottawa, ON, Canada, K1H 8L6. · Monash Department of Clinical Epidemiology, Cabrini Hospital, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Suite 41, Cabrini Medical Centre, 183 Wattletree Road, Malvern, Victoria, Australia, 3144. · Department of General Internal Medicine, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1465, Houston, Texas, USA, 77030. · Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, K1H 8M5. · Department of Epidemiology and Community Medicine, University of Ottawa, Room H1281, 40 Ruskin Street, Ottawa, ON, Canada, K1Y 4W7. ·Cochrane Database Syst Rev · Pubmed #28282491.

ABSTRACT: BACKGROUND: Biologic disease-modifying anti-rheumatic drugs (DMARDs: referred to as biologics) are effective in treating rheumatoid arthritis (RA), however there are few head-to-head comparison studies. Our systematic review, standard meta-analysis and network meta-analysis (NMA) updates the 2009 Cochrane overview, 'Biologics for rheumatoid arthritis (RA)' and adds new data. This review is focused on biologic or tofacitinib therapy in people with RA who had previously been treated unsuccessfully with biologics. OBJECTIVES: To compare the benefits and harms of biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib versus comparator (placebo or methotrexate (MTX)/other DMARDs) in people with RA, previously unsuccessfully treated with biologics. METHODS: On 22 June 2015 we searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, and Embase; and trials registries (WHO trials register, Clinicaltrials.gov). We carried out article selection, data extraction, and risk of bias and GRADE assessments in duplicate. We calculated direct estimates with 95% confidence intervals (CI) using standard meta-analysis. We used a Bayesian mixed treatment comparison (MTC) approach for NMA estimates with 95% credible intervals (CrI). We converted odds ratios (OR) to risk ratios (RR) for ease of understanding. We have also presented results in absolute measures as risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB). Outcomes measured included four benefits (ACR50, function measured by Health Assessment Questionnaire (HAQ) score, remission defined as DAS < 1.6 or DAS28 < 2.6, slowing of radiographic progression) and three harms (withdrawals due to adverse events, serious adverse events, and cancer). MAIN RESULTS: This update includes nine new RCTs for a total of 12 RCTs that included 3364 participants. The comparator was placebo only in three RCTs (548 participants), MTX or other traditional DMARD in six RCTs (2468 participants), and another biologic in three RCTs (348 participants). Data were available for four tumor necrosis factor (TNF)-biologics: (certolizumab pegol (1 study; 37 participants), etanercept (3 studies; 348 participants), golimumab (1 study; 461 participants), infliximab (1 study; 27 participants)), three non-TNF biologics (abatacept (3 studies; 632 participants), rituximab (2 studies; 1019 participants), and tocilizumab (2 studies; 589 participants)); there was only one study for tofacitinib (399 participants). The majority of the trials (10/12) lasted less than 12 months.We judged 33% of the studies at low risk of bias for allocation sequence generation, allocation concealment and blinding, 25% had low risk of bias for attrition, 92% were at unclear risk for selective reporting; and 92% had low risk of bias for major baseline imbalance. We downgraded the quality of the evidence for most outcomes to moderate or low due to study limitations, heterogeneity, or rarity of direct comparator trials. Biologic monotherapy versus placeboCompared to placebo, biologics were associated with clinically meaningful and statistically significant improvement in RA as demonstrated by higher ACR50 and RA remission rates. RR was 4.10 for ACR50 (95% CI 1.97 to 8.55; moderate-quality evidence); absolute benefit RD 14% (95% CI 6% to 21%); and NNTB = 8 (95% CI 4 to 23). RR for RA remission was 13.51 (95% CI 1.85 to 98.45, one study available; moderate-quality evidence); absolute benefit RD 9% (95% CI 5% to 13%); and NNTB = 11 (95% CI 3 to 136). Results for withdrawals due to adverse events and serious adverse events did not show any statistically significant or clinically meaningful differences. There were no studies available for analysis for function measured by HAQ, radiographic progression, or cancer outcomes. There were not enough data for any of the outcomes to look at subgroups. Biologic + MTX versus active comparator (MTX/other traditional DMARDs)Compared to MTX/other traditional DMARDs, biologic + MTX was associated with a clinically meaningful and statistically significant improvement in ACR50, function measured by HAQ, and RA remission rates in direct comparisons. RR for ACR50 was 4.07 (95% CI 2.76 to 5.99; high-quality evidence); absolute benefit RD 16% (10% to 21%); NNTB = 7 (95% CI 5 to 11). HAQ scores showed an improvement with a mean difference (MD) of 0.29 (95% CI 0.21 to 0.36; high-quality evidence); absolute benefit RD 9.7% improvement (95% CI 7% to 12%); and NNTB = 5 (95% CI 4 to 7). Remission rates showed an improved RR of 20.73 (95% CI 4.13 to 104.16; moderate-quality evidence); absolute benefit RD 10% (95% CI 8% to 13%); and NNTB = 17 (95% CI 4 to 96), among the biologic + MTX group compared to MTX/other DMARDs. There were no studies for radiographic progression. Results were not clinically meaningful or statistically significantly different for withdrawals due to adverse events or serious adverse events, and were inconclusive for cancer. Tofacitinib monotherapy versus placeboThere were no published data. Tofacitinib + MTX versus active comparator (MTX)In one study, compared to MTX, tofacitinib + MTX was associated with a clinically meaningful and statistically significant improvement in ACR50 (RR 3.24; 95% CI 1.78 to 5.89; absolute benefit RD 19% (95% CI 12% to 26%); NNTB = 6 (95% CI 3 to 14); moderate-quality evidence), and function measured by HAQ, MD 0.27 improvement (95% CI 0.14 to 0.39); absolute benefit RD 9% (95% CI 4.7% to 13%), NNTB = 5 (95% CI 4 to 10); high-quality evidence). RA remission rates were not statistically significantly different but the observed difference may be clinically meaningful (RR 15.44 (95% CI 0.93 to 256.1; high-quality evidence); absolute benefit RD 6% (95% CI 3% to 9%); NNTB could not be calculated. There were no studies for radiographic progression. There were no statistically significant or clinically meaningful differences for withdrawals due to adverse events and serious adverse events, and results were inconclusive for cancer. AUTHORS' CONCLUSIONS: Biologic (with or without MTX) or tofacitinib (with MTX) use was associated with clinically meaningful and statistically significant benefits (ACR50, HAQ, remission) compared to placebo or an active comparator (MTX/other traditional DMARDs) among people with RA previously unsuccessfully treated with biologics.No studies examined radiographic progression. Results were not clinically meaningful or statistically significant for withdrawals due to adverse events and serious adverse events, and were inconclusive for cancer.

20 Review EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. 2017

Smolen, Josef S / Landewé, Robert / Bijlsma, Johannes / Burmester, Gerd / Chatzidionysiou, Katerina / Dougados, Maxime / Nam, Jackie / Ramiro, Sofia / Voshaar, Marieke / van Vollenhoven, Ronald / Aletaha, Daniel / Aringer, Martin / Boers, Maarten / Buckley, Chris D / Buttgereit, Frank / Bykerk, Vivian / Cardiel, Mario / Combe, Bernard / Cutolo, Maurizio / van Eijk-Hustings, Yvonne / Emery, Paul / Finckh, Axel / Gabay, Cem / Gomez-Reino, Juan / Gossec, Laure / Gottenberg, Jacques-Eric / Hazes, Johanna M W / Huizinga, Tom / Jani, Meghna / Karateev, Dmitry / Kouloumas, Marios / Kvien, Tore / Li, Zhanguo / Mariette, Xavier / McInnes, Iain / Mysler, Eduardo / Nash, Peter / Pavelka, Karel / Poór, Gyula / Richez, Christophe / van Riel, Piet / Rubbert-Roth, Andrea / Saag, Kenneth / da Silva, Jose / Stamm, Tanja / Takeuchi, Tsutomu / Westhovens, René / de Wit, Maarten / van der Heijde, Désirée. ·Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria. · Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands. · Zuyderland Medical Center, Heerlen, The Netherlands. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany. · Rheumatology Department, Karolinska Institute, Stockholm, Sweden. · Rhumatologie B, Hopital Cochin, Paris, France. · NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK. · Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. · Department of Psychology, Health and Technology, University of Twente, Enschede, The Netherlands. · Division of Rheumatology, Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. · Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Birmingham NIHR Wellcome Trust Clinical Research Facility, Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK. · Department of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, New York, USA. · Rebecca McDonald Center for Arthritis & Autoimmune Disease, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. · Centro de Investigación Clínica de Morelia SC, Michoacán, México. · Rheumatology Department, Lapeyronie Hospital, Montpellier University, UMR 5535, Montpellier, France. · Research Laboratory and Division of Clinical Rheumatology, University of Genoa, Genoa, Italy. · Department of Patient & Care and Department of Rheumatology, University of Maastricht, Maastricht, The Netherlands. · Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland. · Fundación Ramón Dominguez, Hospital Clinico Universitario, Santiago, Spain. · Department of Rheumatology, Sorbonne Universités, Pitié Salpêtrière Hospital, Paris, France. · Institut de Biologie Moléculaire et Cellulaire, Immunopathologie, et Chimie Thérapeutique, Strasbourg University Hospital and University of Strasbourg, CNRS, Strasbourg, France. · Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. · Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK. · V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation. · European League Against Rheumatism, Zurich, Switzerland. · Cyprus League against Rheumatism, Nicosia, Cyprus. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Department of Rheumatology and Immunology, Beijing University People's Hospital, Beijing, China. · Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, INSERM U1184, Center for Immunology of viral Infections and Autoimmune Diseases (IMVA), Le Kremlin Bicêtre, France. · Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. · Organización Médica de Investigación, Buenos Aires, Argentina. · Department of Medicine, University of Queensland, Queensland, Australia. · Institute of Rheumatology and Clinic of Rheumatology, Charles University, Prague, Czech Republic. · National Institute of Rheumatology and Physiotherapy, Semmelweis University, Budapest, Hungary. · Rheumatology Department, FHU ACRONIM, Pellegrin Hospital and UMR CNRS 5164, Bordeaux University, Bordeaux, France. · Department of Rheumatology, Bernhoven, Uden, The Netherlands. · University of Cologne, Cologne, Germany. · Division of Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Serviço de Reumatologia, Centro Hospitalar e Universitário de Coimbra Praceta Mota Pinto, Coimbra, Portugal. · Section for Outcomes Research, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. · Keio University School of Medicine, Keio University Hospital, Tokyo, Japan. · Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium. · Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Department Medical Humanities, VU Medical Centre, Amsterdam, The Netherlands. ·Ann Rheum Dis · Pubmed #28264816.

ABSTRACT: Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.

21 Review Defining the optimal biological monotherapy in rheumatoid arthritis: A systematic review and meta-analysis of randomised trials. 2017

Tarp, Simon / Furst, Daniel E / Dossing, Anna / Østergaard, Mikkel / Lorenzen, Tove / Hansen, Michael S / Singh, Jasvinder A / Choy, Ernest H / Boers, Maarten / Suarez-Almazor, Maria E / Kristensen, Lars E / Bliddal, Henning / Christensen, Robin. ·Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg og Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark. Electronic address: simon.tarp@regionh.dk. · Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA. · Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg og Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark. · Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Glostrup Hospital, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. · Department of Rheumatology, Diagnostic Centre, Silkeborg Regional Hospital, Copenhagen, Denmark. · ReumaKlinik Roskilde, Roskilde, Denmark; Gildhøj Privathospital, Brøndby, Denmark. · Medicine Service and Center for Surgical Medical Acute care Research and Transitions, VA Medical Center, Birmingham, AL; Department of Medicine at School of Medicine, Division of Epidemiology at School of Public Health, University of Alabama, Birmingham, AL; Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN. · Section of Rheumatology, Arthritis Research UK and Health and Care Research Wales CREATE Centre, Cardiff University School of Medicine, Cardiff, UK. · Department of Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The Netherlands. · Section of Rheumatology and Clinical Immunology, University of Texas MD Anderson Cancer Center, Houston, TX. ·Semin Arthritis Rheum · Pubmed #27769592.

ABSTRACT: OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800. RESULTS: The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included "DMARD-naïve", and 20 "DMARD-Inadequate responder" (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p < 0.05) to placebo (i.e., no DMARD treatment) with regard to ACR50. Etanercept and rituximab were superior to anakinra (p = 0.018 and p = 0.049, respectively). Tocilizumab was superior to adalimumab (p = 0.0082), anakinra (p = 0.0083), certolizumab (p = 0.037), and golimumab (p = 0.049). No differences among etanercept, tocilizumab, and rituximab were found (p > 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068). CONCLUSIONS: Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.

22 Review Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane Systematic Review and network meta-analysis (NMA). 2016

Singh, Jasvinder A / Hossain, Alomgir / Tanjong Ghogomu, Elizabeth / Mudano, Amy S / Tugwell, Peter / Wells, George A. ·Department of Medicine, Birmingham VA Medical Center, Faculty Office Tower 805B, 510 20th Street South, Birmingham, AL, USA, 35294. ·Cochrane Database Syst Rev · Pubmed #27855242.

ABSTRACT: BACKGROUND: We performed a systematic review, a standard meta-analysis and network meta-analysis (NMA), which updates the 2009 Cochrane Overview, 'Biologics for rheumatoid arthritis (RA)'. This review is focused on biologic monotherapy in people with RA in whom treatment with traditional disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) had failed (MTX/other DMARD-experienced). OBJECTIVES: To assess the benefits and harms of biologic monotherapy (includes anti-tumor necrosis factor (TNF) (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) or non-TNF (abatacept, anakinra, rituximab, tocilizumab)) or tofacitinib monotherapy (oral small molecule) versus comparator (placebo or MTX/other DMARDs) in adults with RA who were MTX/other DMARD-experienced. METHODS: We searched for randomized controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2015, Issue 6, June), MEDLINE (via OVID 1946 to June 2015), and Embase (via OVID 1947 to June 2015). Article selection, data extraction and risk of bias and GRADE assessments were done in duplicate. We calculated direct estimates with 95% confidence intervals (CI) using standard meta-analysis. We used a Bayesian mixed treatment comparisons (MTC) approach for NMA estimates with 95% credible intervals (CrI). We converted odds ratios (OR) to risk ratios (RR) for ease of understanding. We calculated absolute measures as risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB). MAIN RESULTS: This update includes 40 new RCTs for a total of 46 RCTs, of which 41 studies with 14,049 participants provided data. The comparator was placebo in 16 RCTs (4,532 patients), MTX or other DMARD in 13 RCTs (5,602 patients), and another biologic in 12 RCTs (3,915 patients). Monotherapy versus placeboBased on moderate-quality direct evidence, biologic monotherapy (without concurrent MTX/other DMARDs) was associated with a clinically meaningful and statistically significant improvement in American College of Rheumatology score (ACR50) and physical function, as measured by the Health Assessment Questionnaire (HAQ) versus placebo. RR was 4.68 for ACR50 (95% CI, 2.93 to 7.48); absolute benefit RD 23% (95% CI, 18% to 29%); and NNTB = 5 (95% CI, 3 to 8). The mean difference (MD) was -0.32 for HAQ (95% CI, -0.42 to -0.23; a negative sign represents greater HAQ improvement); absolute benefit of -10.7% (95% CI, -14% to -7.7%); and NNTB = 4 (95% CI, 3 to 5). Direct and NMA estimates for TNF biologic, non-TNF biologic or tofacitinib monotherapy showed similar results for ACR50 , downgraded to moderate-quality evidence. Direct and NMA estimates for TNF biologic, anakinra or tofacitinib monotherapy showed a similar results for HAQ versus placebo with mostly moderate quality evidence.Based on moderate-quality direct evidence, biologic monotherapy was associated with a clinically meaningful and statistically significant greater proportion of disease remission versus placebo with RR 1.12 (95% CI 1.03 to 1.22); absolute benefit 10% (95% CI, 3% to 17%; NNTB = 10 (95% CI, 8 to 21)).Based on low-quality direct evidence, results for biologic monotherapy for withdrawals due to adverse events and serious adverse events were inconclusive, with wide confidence intervals encompassing the null effect and evidence of an important increase. The direct estimate for TNF monotherapy for withdrawals due to adverse events showed a clinically meaningful and statistically significant result with RR 2.02 (95% CI, 1.08 to 3.78), absolute benefit RD 3% (95% CI,1% to 4%), based on moderate-quality evidence. The NMA estimates for TNF biologic, non-TNF biologic, anakinra, or tofacitinib monotherapy for withdrawals due to adverse events and for serious adverse events were all inconclusive and downgraded to low-quality evidence. Monotherapy versus active comparator (MTX/other DMARDs)Based on direct evidence of moderate quality, biologic monotherapy (without concurrent MTX/other DMARDs) was associated with a clinically meaningful and statistically significant improvement in ACR50 and HAQ scores versus MTX/other DMARDs with a RR of 1.54 (95% CI, 1.14 to 2.08); absolute benefit 13% (95% CI, 2% to 23%), NNTB = 7 (95% CI, 4 to 26) and a mean difference in HAQ of -0.27 (95% CI, -0.40 to -0.14); absolute benefit of -9% (95% CI, -13.3% to -4.7%), NNTB = 2 (95% CI, 2 to 4). Direct and NMA estimates for TNF monotherapy and NMA estimate for non-TNF biologic monotherapy for ACR50 showed similar results, based on moderate-quality evidence. Direct and NMA estimates for non-TNF biologic monotherapy, but not TNF monotherapy, showed similar HAQ improvements , based on mostly moderate-quality evidence.There were no statistically significant or clinically meaningful differences for direct estimates of biologic monotherapy versus active comparator for RA disease remission. NMA estimates showed a statistically significant and clinically meaningful difference versus active comparator for TNF monotherapy (absolute improvement 7% (95% CI, 2% to 14%)) and non-TNF monotherapy (absolute improvement 19% (95% CrI, 7% to 36%)), both downgraded to moderate quality.Based on moderate-quality direct evidence from a single study, radiographic progression (scale 0 to 448) was statistically significantly reduced in those on biologic monotherapy versus active comparator, MD -4.34 (95% CI, -7.56 to -1.12), though the absolute reduction was small, -0.97% (95% CI, -1.69% to -0.25%). We are not sure of the clinical relevance of this reduction.Direct and NMA evidence (downgraded to low quality), showed inconclusive results for withdrawals due to adverse events, serious adverse events and cancer, with wide confidence intervals encompassing the null effect and evidence of an important increase. AUTHORS' CONCLUSIONS: Based mostly on RCTs of six to 12-month duration in people with RA who had previously experienced and failed treatment with MTX/other DMARDs, biologic monotherapy improved ACR50, function and RA remission rates compared to placebo or MTX/other DMARDs.Radiographic progression was reduced versus active comparator, although the clinical significance was unclear.Results were inconclusive for whether biologic monotherapy was associated with an increased risk of withdrawals due to adverse events, serious adverse events or cancer, versus placebo (no data on cancer) or MTX/other DMARDs.

23 Review Adherence and Persistence with Methotrexate in Rheumatoid Arthritis: A Systematic Review. 2016

Curtis, Jeffrey R / Bykerk, Vivian P / Aassi, Maher / Schiff, Michael. ·From the Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama; Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York; Rheumatology Division, University of Colorado School of Medicine, Greenwood Village, Colorado, USA; Department of Rheumatology, Mount Sinai Hospital, Toronto, Ontario, Canada; F. Hoffmann-La Roche Ltd., Basel, Switzerland. jcurtis@uab.edu. · J.R. Curtis, MD, MS, MPH, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; V.P. Bykerk, MD, Inflammatory Arthritis Center, Hospital for Special Surgery, and Department of Rheumatology, Mount Sinai Hospital; M. Aassi, MD, F. Hoffmann-La Roche Ltd.; M. Schiff, MD, Rheumatology Division, University of Colorado School of Medicine. jcurtis@uab.edu. · From the Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama; Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York; Rheumatology Division, University of Colorado School of Medicine, Greenwood Village, Colorado, USA; Department of Rheumatology, Mount Sinai Hospital, Toronto, Ontario, Canada; F. Hoffmann-La Roche Ltd., Basel, Switzerland. · J.R. Curtis, MD, MS, MPH, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; V.P. Bykerk, MD, Inflammatory Arthritis Center, Hospital for Special Surgery, and Department of Rheumatology, Mount Sinai Hospital; M. Aassi, MD, F. Hoffmann-La Roche Ltd.; M. Schiff, MD, Rheumatology Division, University of Colorado School of Medicine. ·J Rheumatol · Pubmed #27803341.

ABSTRACT: OBJECTIVE: Medication adherence in patients with rheumatoid arthritis (RA) is typically suboptimal. Nonadherence has been associated with symptom worsening and increased disability. We systematically reviewed published clinical studies to evaluate methotrexate (MTX) adherence and persistence, factors associated with MTX adherence and persistence, and the effect of MTX nonadherence on clinical outcomes in RA. METHODS: MEDLINE and Embase were systematically searched (inception to February 2016) using relevant keywords. Observational or interventional clinical studies in patients with RA that specifically reported adherence to or persistence with MTX were included. Data were extracted using a predesigned, standardized template that included study design, patient demographics, and relevant outcomes. Main outcomes were MTX adherence and persistence rates in patients with RA treated with MTX and factors associated with MTX adherence and persistence. RESULTS: Of 365 references screened, 31 articles met inclusion criteria and another 10 were identified from searching reference lists. Estimates of MTX adherence varied from study to study because of heterogeneity in patient populations, duration of followup, definitions of adherence, and methods of assessment. Rates of MTX persistence ranged from 50% to 94% at 1 year and 25% to 79% at 5 years. No clear trends were identified in factors that influence MTX adherence and persistence. Two studies suggested that MTX adherence was associated with superior clinical outcomes. CONCLUSION: MTX adherence and persistence are highly variable in patients with RA. Research is necessary to determine the effect of nonadherence on health outcomes and to identify independent predictors of nonadherence to inform evidence-based interventions.

24 Review Infections With Biologics in Rheumatoid Arthritis and Related Conditions: a Scoping Review of Serious or Hospitalized Infections in Observational Studies. 2016

Singh, Jasvinder A. ·Department of Medicine, School of Medicine, University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA. Jasvinder.md@gmail.com. · Division of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA. Jasvinder.md@gmail.com. · Medicine Service, Birmingham VA Medical Center, Birmingham, AL, USA. Jasvinder.md@gmail.com. · Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA. Jasvinder.md@gmail.com. ·Curr Rheumatol Rep · Pubmed #27613285.

ABSTRACT: Biologic use is a major advance in the treatment of several autoimmune conditions, including rheumatoid arthritis. In this review, we summarize key studies of serious/hospitalized infections in rheumatoid arthritis (RA). RA is a risk factor for infections. High RA disease activity is associated with higher risk of serious infection. The risk of serious infections with tumor necrosis factor inhibitor (TNFi) biologics is increased in the first 6 months of initiating therapy, and this risk was higher compared to the use of traditional disease-modifying anti-rheumatic drugs (DMARDs). Emerging data also suggest that biologics may differ from each other regarding the risk of serious or hospitalized infections. Past history of serious infections, glucocorticoid dose, and older age were other important predictors of risk of serious infections in patients treated with biologics.

25 Review Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis. 2016

Singh, Jasvinder A / Hossain, Alomgir / Tanjong Ghogomu, Elizabeth / Kotb, Ahmed / Christensen, Robin / Mudano, Amy S / Maxwell, Lara J / Shah, Nipam P / Tugwell, Peter / Wells, George A. ·Department of Medicine, Birmingham VA Medical Center, Faculty Office Tower 805B, 510 20th Street South, Birmingham, AL, USA, 35294. ·Cochrane Database Syst Rev · Pubmed #27175934.

ABSTRACT: BACKGROUND: This is an update of the 2009 Cochrane overview and network meta-analysis (NMA) of biologics for rheumatoid arthritis (RA). OBJECTIVES: To assess the benefits and harms of nine biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib, versus comparator (MTX, DMARD, placebo (PL), or a combination) in adults with rheumatoid arthritis who have failed to respond to methotrexate (MTX) or other disease-modifying anti-rheumatic drugs (DMARDs), i.e., MTX/DMARD incomplete responders (MTX/DMARD-IR). METHODS: We searched for randomized controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (via The Cochrane Library Issue 6, June 2015), MEDLINE (via OVID 1946 to June 2015), and EMBASE (via OVID 1947 to June 2015). Data extraction, risk of bias and GRADE assessments were done in duplicate. We calculated both direct estimates using standard meta-analysis and used Bayesian mixed treatment comparisons approach for NMA estimates to calculate odds ratios (OR) and 95% credible intervals (CrI). We converted OR to risk ratios (RR) which are reported in the abstract for the ease of interpretation. MAIN RESULTS: This update included 73 new RCTs for a total of 90 RCTs; 79 RCTs with 32,874 participants provided usable data. Few trials were at high risk of bias for blinding of assessors/participants (13% to 21%), selective reporting (4%) or major baseline imbalance (8%); a large number had unclear risk of bias for random sequence generation (68%) or allocation concealment (74%).Based on direct evidence of moderate quality (downgraded for inconsistency), biologic+MTX/DMARD was associated with a statistically significant and clinically meaningful improvement in ACR50 versus comparator (RR 2.71 (95% confidence interval (CI) 2.36 to 3.10); absolute benefit 24% more patients (95% CI 19% to 29%), number needed to treat for an additional beneficial outcome (NNTB) = 5 (4 to 6). NMA estimates for ACR50 in tumor necrosis factor (TNF) biologic+MTX/DMARD (RR 3.23 (95% credible interval (Crl) 2.75 to 3.79), non-TNF biologic+MTX/DMARD (RR 2.99; 95% Crl 2.36 to 3.74), and anakinra + MTX/DMARD (RR 2.37 (95% Crl 1.00 to 4.70) were similar to the direct estimates.Based on direct evidence of moderate quality (downgraded for inconsistency), biologic+MTX/DMARD was associated with a clinically and statistically important improvement in function measured by the Health Assessment Questionnaire (0 to 3 scale, higher = worse function) with a mean difference (MD) based on direct evidence of -0.25 (95% CI -0.28 to -0.22); absolute benefit of -8.3% (95% CI -9.3% to -7.3%), NNTB = 3 (95% CI 2 to 4). NMA estimates for TNF biologic+MTX/DMARD (absolute benefit, -10.3% (95% Crl -14% to -6.7%) and non-TNF biologic+MTX/DMARD (absolute benefit, -7.3% (95% Crl -13.6% to -0.67%) were similar to respective direct estimates.Based on direct evidence of moderate quality (downgraded for inconsistency), biologic+MTX/DMARD was associated with clinically and statistically significantly greater proportion of participants achieving remission in RA (defined by disease activity score DAS < 1.6 or DAS28 < 2.6) versus comparator (RR 2.81 (95% CI, 2.23 to 3.53); absolute benefit 18% more patients (95% CI 12% to 25%), NNTB = 6 (4 to 9)). NMA estimates for TNF biologic+MTX/DMARD (absolute improvement 17% (95% Crl 11% to 23%)) and non-TNF biologic+MTX/DMARD (absolute improvement 19% (95% Crl 12% to 28%) were similar to respective direct estimates.Based on direct evidence of moderate quality (downgraded for inconsistency), radiographic progression (scale 0 to 448) was statistically significantly reduced in those on biologics + MTX/DMARDs versus comparator, MD -2.61 (95% CI -4.08 to -1.14). The absolute reduction was small, -0.58% (95% CI -0.91% to -0.25%) and we are unsure of the clinical relevance of this reduction. NMA estimates of TNF biologic+MTX/DMARD (absolute reduction -0.67% (95% Crl -1.4% to -0.12%) and non-TNF biologic+MTX/DMARD (absolute reduction, -0.68% (95% Crl -2.36% to 0.92%)) were similar to respective direct estimates.Based on direct evidence of moderate quality (downgraded for imprecision), results for withdrawals due to adverse events were inconclusive, with wide confidence intervals encompassing the null effect and evidence of an important increase in withdrawals, RR 1.11 (95% CI 0.96 to 1.30). The NMA estimates of TNF biologic+MTX/DMARD (RR 1.24 (95% Crl 0.99 to 1.57)) and non-TNF biologic+MTX/DMARD (RR 1.20 (95% Crl 0.87 to 1.67)) were similarly inconclusive and downgraded to low for both imprecision and indirectness.Based on direct evidence of high quality, biologic+MTX/DMARD was associated with clinically significantly increased risk (statistically borderline significant) of serious adverse events on biologic+MTX/DMARD (Peto OR [can be interpreted as RR due to low event rate] 1.12 (95% CI 0.99 to 1.27); absolute risk 1% (0% to 2%), As well, the NMA estimate for TNF biologic+MTX/DMARD (Peto OR 1.20 (95% Crl 1.01 to 1.43)) showed moderate quality evidence of an increase in the risk of serious adverse events. The other two NMA estimates were downgraded to low quality due to imprecision and indirectness and had wide confidence intervals resulting in uncertainty around the estimates: non-TNF biologics + MTX/DMARD: 1.07 (95% Crl 0.89 to 1.29) and anakinra: RR 1.06 (95% Crl 0.65 to 1.75).Based on direct evidence of low quality (downgraded for serious imprecision), results were inconclusive for cancer (Peto OR 1.07 (95% CI 0.68 to 1.68) for all biologic+MTX/DMARD combinations. The NMA estimates of TNF biologic+MTX/DMARD (Peto OR 1.21 (95% Crl 0.63 to 2.38) and non-TNF biologic+MTX/DMARD (Peto OR 0.99 (95% Crl 0.58 to 1.78)) were similarly inconclusive and downgraded to low quality for both imprecision and indirectness.Main results text shows the results for tofacitinib and differences between medications. AUTHORS' CONCLUSIONS: Based primarily on RCTs of 6 months' to 12 months' duration, there is moderate quality evidence that the use of biologic+MTX/DMARD in people with rheumatoid arthritis who have failed to respond to MTX or other DMARDs results in clinically important improvement in function and higher ACR50 and remission rates, and increased risk of serious adverse events than the comparator (MTX/DMARD/PL; high quality evidence). Radiographic progression is slowed but its clinical relevance is uncertain. Results were inconclusive for whether biologics + MTX/DMARDs are associated with an increased risk of cancer or withdrawals due to adverse events.

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