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Spinal Diseases: HELP
Articles by Alan M. Mendelsohn
Based on 9 articles published since 2009
(Why 9 articles?)
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Between 2009 and 2019, A. Mendelsohn wrote the following 9 articles about Spinal Diseases.
 
+ Citations + Abstracts
1 Clinical Trial Ustekinumab Treatment and Improvement of Physical Function and Health-Related Quality of Life in Patients With Psoriatic Arthritis. 2016

Rahman, Proton / Puig, Lluis / Gottlieb, Alice B / Kavanaugh, Arthur / McInnes, Iain B / Ritchlin, Christopher / Li, Shu / Wang, Yuhua / Song, Michael / Mendelsohn, Alan / Han, Chenglong / Anonymous70877. ·Memorial University, Newfoundland, Canada. · Hospital de la Santa Creu i Sant Pau, Universitat Autònoa de Barcelona, Barcelona, Spain. · Tufts University School of Medicine, Boston, Massachusetts. · University of California, San Diego. · University of Glasgow, Glasgow, Scotland. · University of Rochester, Rochester, New York. · Janssen Research & Development, LLC, Spring House, Pennsylvania. · Janssen Global Services, LLC, Malvern, Pennsylvania. ·Arthritis Care Res (Hoboken) · Pubmed #27483458.

ABSTRACT: OBJECTIVE: To examine the effects of ustekinumab on patient-reported outcomes (PROs) in PSUMMIT 1 and PSUMMIT 2 patients with active psoriatic arthritis (PsA) who were methotrexate (MTX) naive, MTX experienced, or anti-tumor necrosis factor (TNF) experienced. METHODS: Patients in the phase 3, PSUMMIT 1 (n = 615) and PSUMMIT 2 (n = 312) studies randomly (1:1:1) received placebo, ustekinumab 45-mg, or ustekinumab 90-mg subcutaneous injections at weeks 0, 4, 16, 28, 40, and 52. The PROs (Health Assessment Questionnaire [HAQ] disability index [DI], Dermatology Life Quality Index [DLQI], 36-Item Short Form [SF-36] health survey physical (PCS) and mental component summary scores, patient assessments of pain and disease activity, and impact of disease on productivity) were assessed at weeks 0, 24, and 52. In these post hoc analyses, outcomes were compared between the ustekinumab and placebo groups for 3 mutually exclusive antecedent-exposure populations from the combined studies: MTX/anti-TNF naive (placebo, n = 56; 45 mg, n = 58; and 90 mg, n = 66), MTX experienced, biologic agent naive (placebo, n = 192; 45 mg, n = 190; and 90 mg, n = 185), and anti-TNF experienced with or without MTX (placebo, n = 62; 45 mg, n = 60; and 90 mg, n = 58). RESULTS: At week 24, mean improvements from baseline in HAQ DI, DLQI, and SF-36 PCS scores were significantly greater in both ustekinumab groups versus placebo across antecedent-exposure groups. Greater proportions of ustekinumab-treated than placebo-treated patients (all P < 0.05) had clinically meaningful improvements in HAQ DI (≥0.3), DLQI (≥5), and SF-36 (≥5) scores at week 24, irrespective of drug exposure. Improvements in pain, disease activity, and impact of disease on productivity were similar, and benefits were maintained through week 52. CONCLUSION: Significant improvements in PROs with ustekinumab versus placebo were observed in 3 antecedent-exposure populations of PsA patients, including those with prior MTX and anti-TNF use.

2 Clinical Trial Maintenance of Clinical Efficacy and Radiographic Benefit Through Two Years of Ustekinumab Therapy in Patients With Active Psoriatic Arthritis: Results From a Randomized, Placebo-Controlled Phase III Trial. 2015

Kavanaugh, Arthur / Puig, Lluís / Gottlieb, Alice B / Ritchlin, Christopher / Li, Shu / Wang, Yuhua / Mendelsohn, Alan M / Song, Michael / Zhu, Yaowei / Rahman, Proton / McInnes, Iain B / Anonymous350834. ·University of California, San Diego, La Jolla, California. · Universitat Autònoma de Barcelona, Barcelona, Spain. · Tufts Medical Center, Boston, Massachusetts. · University of Rochester, Rochester, New York. · Janssen Research & Development, Spring House, Pennsylvania. · Memorial University, St. John's, Newfoundland and Labrador, Canada. · University of Glasgow, Glasgow, Scotland. ·Arthritis Care Res (Hoboken) · Pubmed #26097039.

ABSTRACT: OBJECTIVE: To evaluate the efficacy and safety of ustekinumab through 2 years in adult patients with active psoriatic arthritis (PsA). METHODS: A total of 615 adult patients with active PsA were randomized to placebo, ustekinumab 45 mg, or ustekinumab 90 mg, at weeks 0, 4, and every 12 weeks through week 88 (last dose). At week 16, patients with <5% improvement in both tender and swollen joint counts entered blinded early escape (placebo to 45 mg, 45 mg to 90 mg, and 90 mg to 90 mg). All remaining placebo patients crossed over to ustekinumab 45 mg at week 24. Clinical efficacy measures included American College of Rheumatology criteria for 20% improvement (ACR20), Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), and ≥75% improvement in the Psoriasis Area and Severity Index (PASI75). Radiographic progression was evaluated using the modified Sharp/van der Heijde score (SHS). RESULTS: At week 100, ACR20, DAS28-CRP moderate/good response, and PASI75 rates ranged from 56.7-63.6%, 71.9-76.7%, and 63.9-72.5%, respectively, across the 3 treatment groups. In both ustekinumab groups, the median percent improvement in dactylitis and enthesitis was 100% at week 100. The mean changes in SHS score from week 52 to week 100 were similar to those observed from week 0 to week 52 in the ustekinumab groups. Through week 108, 70.7% and 9.7% of patients had an adverse event (AE) or serious AE, respectively. The rates and type of AEs were similar between the dose groups. CONCLUSION: Clinical and radiographic benefits from ustekinumab treatment were maintained through week 100 in the PSUMMIT 1 study. No unexpected safety events were observed; the safety profile of ustekinumab in this population was similar to that previously observed in psoriasis patients treated with ustekinumab.

3 Clinical Trial Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials. 2014

Kavanaugh, Arthur / Ritchlin, Christopher / Rahman, Proton / Puig, Lluis / Gottlieb, Alice B / Li, Shu / Wang, Yuhua / Noonan, Lenore / Brodmerkel, Carrie / Song, Michael / Mendelsohn, Alan M / McInnes, Iain B / Anonymous9310785. ·Rheumatology Allergy and Immunology Division, University of California-San Diego, , La Jolla, California, USA. ·Ann Rheum Dis · Pubmed #24553909.

ABSTRACT: OBJECTIVE: Evaluate ustekinumab, an anti-interleukin (IL)-12 and IL-23 antibody, effects on radiographic progression in psoriatic arthritis (PsA). METHODS: We conducted preplanned integrated analyses of combined radiographic data from PSUMMIT-1 and PSUMMIT-2 phase 3, randomised, controlled trials. Patients had active PsA despite prior conventional and/or biologic disease-modifying antirheumatic drugs (≥5/66 swollen, ≥5/68 tender joints, C-reactive protein ≥3.0 mg/L, documented plaque psoriasis). Patients (PSUMMIT-1, n=615; PSUMMIT-2, n=312) were randomised to ustekinumab 45 mg, 90 mg, or placebo, at weeks (wk) 0, 4 and every (q) 12 wks. At wk 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape. All other placebo patients received ustekinumab 45 mg at wk 24 and wk 28, then q 12 wks. Radiographs of hands/feet at wks 0/24/52 were assessed using PsA-modified van der Heijde-Sharp (vdH-S) scores; combined PSUMMIT-1 and PSUMMIT-2 changes in total vdH-S scores from wk 0 to wk 24 comprised the prespecified primary radiographic analysis. Treatment effects were assessed using analysis of variance on van der Waerden normal scores (factors=treatment, baseline methotrexate usage, and study). RESULTS: Integrated data analysis results indicated that ustekinumab-treated patients (regardless of dose) demonstrated significantly less radiographic progression at wk 24 than did placebo recipients (wk 0-24 total vdH-S score mean changes: 0.4-combined/individual ustekinumab dose groups, 1.0-placebo; all p<0.02). From wk 24 to wk 52, inhibition of radiographic progression was maintained for ustekinumab-treated patients, and progression was substantially reduced among initial placebo recipients who started ustekinumab at wk 16 or wk 24 (wk 24 - wk 52, total vdH-S score mean change: 0.08). CONCLUSIONS: Ustekinumab 45 and 90 mg treatments significantly inhibited radiographic progression of joint damage in patients with active PsA.

4 Clinical Trial Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. 2014

Ritchlin, Christopher / Rahman, Proton / Kavanaugh, Arthur / McInnes, Iain B / Puig, Lluis / Li, Shu / Wang, Yuhua / Shen, Yaung-Kaung / Doyle, Mittie K / Mendelsohn, Alan M / Gottlieb, Alice B / Anonymous3430783. ·Allergy, Immunology & Rheumatology Division, University of Rochester Medical Center, , Rochester, New York, USA. ·Ann Rheum Dis · Pubmed #24482301.

ABSTRACT: OBJECTIVE: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. METHODS: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. RESULTS: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change -0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change -0.13). No unexpected adverse events were observed through week 60. CONCLUSIONS: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients.

5 Clinical Trial Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. 2013

McInnes, Iain B / Kavanaugh, Arthur / Gottlieb, Alice B / Puig, Lluís / Rahman, Proton / Ritchlin, Christopher / Brodmerkel, Carrie / Li, Shu / Wang, Yuhua / Mendelsohn, Alan M / Doyle, Mittie K / Anonymous2900761. ·Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK. iain.mcinnes@glasgow.ac.uk ·Lancet · Pubmed #23769296.

ABSTRACT: BACKGROUND: Many patients with psoriasis develop psoriatic arthritis, a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures. The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis. We did a randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis. METHODS: In this phase 3, multicentre, double-blind, placebo-controlled trial at 104 sites in Europe, North America, and Asia-Pacific, adults with active psoriatic arthritis (≥5 tender and ≥5 swollen joints, C-reactive protein ≥3·0 mg/L) were randomly assigned (1:1:1, by dynamic central randomisation based on an algorithm implemented by an interactive voice-web response system) to 45 mg ustekinumab, 90 mg ustekinumab, or placebo at week 0, week 4, and every 12 weeks thereafter. At week 16, patients with less than 5% improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab (if in the placebo group) or 90 mg ustekinumab (if in the 45 mg group). At week 24, all remaining patients in the placebo group received ustekinumab 45 mg, which they continued at week 28 and every 12 weeks thereafter. Our primary endpoint was 20% or greater improvement in American College of Rheumatology (ACR20) criteria at week 24. This trial is registered with ClinicalTrials.gov (NCT01009086) and EudraCT (2009-012264-14). FINDINGS: Between Nov 30, 2009, and March 30, 2011, 615 patients were randomly assigned-206 to placebo, 205 to 45 mg ustekinumab, and 204 to 90 mg ustekinumab. More ustekinumab-treated (87 of 205 [42·4%] in the 45 mg group and 101 of 204 [49·5%] in the 90 mg group) than placebo-treated (47 of 206 [22·8%]) patients achieved ACR20 at week 24 (p<0·0001 for both comparisons); responses were maintained at week 52. At week 16, proportions of patients with adverse events were similar in the ustekinumab and placebo groups (171 of 409 [41·8%] vs 86 of 205 [42·0%]). INTERPRETATION: Ustekinumab significantly improved active psoriatic arthritis compared with placebo, and might offer an alternative therapeutic mechanism of action to approved biological treatments. FUNDING: Janssen Research & Development.

6 Clinical Trial Population pharmacokinetics of ustekinumab in patients with active psoriatic arthritis. 2010

Zhu, Y W / Mendelsohn, A / Pendley, C / Davis, H M / Zhou, H. ·Pharmacokinetics, Modeling and Simulation, Biologics Clinical Pharmacology, Centocor Research & Development, Inc., 200 Great Valley Parkway, Malvern, PA 19355, USA. yzhu8@its.jnj.com ·Int J Clin Pharmacol Ther · Pubmed #21084039.

ABSTRACT: PURPOSE: To characterize the population pharmacokinetics of subcutaneous ustekinumab, a human IgG1Kappa; monoclonal antibody against interleukin-12/23p40, using data from a randomized, double-blind, placebo-controlled Phase II study in patients with active psoriatic arthritis (PsA). METHODS: A total of 786 quantifiable serum ustekinumab concentrations from 130 patients were analyzed using a nonlinear mixed-effects modeling approach. A 1-compartment model with first-order absorption and elimination was selected as the structural model. RESULTS: The population typical mean (percent relative standard error (%RSE)) values for apparent clearance (CL/F), apparent volume of distribution (V/F), and absorption rate constant (ka) obtained from the final covariate model were 0.465 l × day-1 (5.1%), 14.3 l (4.4%), and 0.427 day-1 (3.9%), respectively. The between-subject variability in CL/F, V/F, and ka were 53.9%, 42.3%, and 82.4%, respectively. Patient body weight and antibody-to-ustekinumab status were significant covariates affecting the CL/F and/or V/F of ustekinumab. None of the other factors evaluated, such as age, sex, race, baseline disease characteristics, concomitant methotrexate or nonsteroidal anti-inflammatory drugs, and past use of immunosuppressives, biologics, systemic corticosteroids, or disease-modifying antirheumatic drugs, were found to have significant effects on the pharmacokinetics of ustekinumab. CONCLUSION: The pharmacokinetics of ustekinumab in patients with PsA are comparable to those in patients with moderate-to-severe plaque psoriasis which was previously investigated.

7 Clinical Trial Effect of ustekinumab on physical function and health-related quality of life in patients with psoriatic arthritis: a randomized, placebo-controlled, phase II trial. 2010

Kavanaugh, Arthur / Menter, Alan / Mendelsohn, Alan / Shen, Yaung-Kaung / Lee, Seina / Gottlieb, Alice B. ·Division of Rheumatology, Allergy, and Immunology, San Diego, CA, USA. akavanaugh@ucsd.edu ·Curr Med Res Opin · Pubmed #20831455.

ABSTRACT: OBJECTIVE: To use data from a phase II clinical trial to evaluate the effect of ustekinumab, a human immunoglobulin monoclonal antibody that binds with high affinity to the shared p40 subunit of human interleukins-12 and -23, on physical disability and health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). METHODS: In this multicenter, double-blind, placebo-controlled, crossover study of ustekinumab, patients with active PsA were randomized (1:1 ratio) to receive either ustekinumab at weeks 0, 1, 2, and 3 and placebo at weeks 12 and 16 (n = 76) or placebo at weeks 0, 1, 2, and 3 and ustekinumab at weeks 12 and 16 (n = 70). Physical function was assessed using the disability index from the Health Assessment Questionnaire-Disability Index (HAQ-DI) in all randomized patients. HRQoL was evaluated using the Dermatology Life Quality Index (DLQI) in a subset of patients (84.9%) with at least 3% body surface area (BSA) psoriasis involvement at baseline. RESULTS: At baseline, overall mean HAQ-DI and DLQI scores were 0.9 and 11.5, respectively, indicating impaired physical function and moderate effect on HRQoL. At week 12, ustekinumab patients had significantly more improvement (decrease) in the mean HAQ-DI (-0.31) and DLQI (-8.6) scores versus placebo (-0.04 and -0.8, respectively; p < 0.001 for both comparisons). At week 12, 58.7% (37/63) of ustekinumab-treated patients had a DLQI score of 0 or 1 (no negative effect of disease or treatment on HRQoL) versus 5.5% (3/55) for placebo (p < 0.001). The results also indicated a positive but weak correlation between improvement in physical function and HRQoL, pain, and skin response as well as between improvement in joint and skin responses in patients receiving ustekinumab or placebo. Potential limitations of the study include the short duration of the placebo-controlled period and the relatively small patient population. CONCLUSION: Ustekinumab significantly improved physical function and HRQoL in patients with PsA and psoriasis involving at least 3% BSA.

8 Article Latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint. 2014

Hu, Chuanpu / Szapary, Philippe O / Mendelsohn, Alan M / Zhou, Honghui. ·Pharmacokinetics and Pharmacometrics, Biologics Clinical Pharmacology, Janssen Research and Development, LLC, 1400 McKean Road, PO Box 776, Spring House, PA, 19477, USA, CHu25@its.jnj.com. ·J Pharmacokinet Pharmacodyn · Pubmed #25038623.

ABSTRACT: Informative exposure-response modeling of clinical endpoints is important in drug development. There has been much recent progress in latent variable modeling of ordered categorical endpoints, including the application of indirect response (IDR) models and accounting for residual correlations between multiple categorical endpoints. This manuscript describes a framework of latent-variable-based IDR models that facilitate easy simultaneous modeling of a continuous and a categorical clinical endpoint. The model was applied to data from two phase III clinical trials of subcutaneously administered ustekinumab for the treatment of psoriatic arthritis, where Psoriasis Area and Severity Index scores and 20, 50, and 70 % improvement in the American College of Rheumatology response criteria were used as efficacy endpoints. Visual predictive check and external validation showed reasonable parameter estimation precision and model performance.

9 Article Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial. 2009

Gottlieb, Alice / Menter, Alan / Mendelsohn, Alan / Shen, Yaung-Kaung / Li, Shu / Guzzo, Cynthia / Fretzin, Scott / Kunynetz, Rod / Kavanaugh, Arthur. ·Tufts Medical Center, Boston, MA, USA. ·Lancet · Pubmed #19217154.

ABSTRACT: BACKGROUND: Since some patients with psoriatic arthritis do not respond to typical drug treatments, alternatives are needed. Findings suggest that interleukins 12 and 23 might affect clinical symptoms and pathological joint changes of psoriatic arthritis. Ustekinumab is a human monoclonal antibody that inhibits receptor-binding of these cytokines. We aimed to assess the efficacy and safety of ustekinumab for psoriatic arthritis in this phase II study. METHODS: We undertook a double-blind, randomised, placebo-controlled, crossover study at 24 sites in North America and Europe. Patients with active psoriatic arthritis were randomly allocated via interactive voice response system to either ustekinumab (90 mg or 63 mg) every week for 4 weeks (weeks 0-3) followed by placebo at weeks 12 and 16 (n=76; Group 1) or placebo (weeks 0-3) and ustekinumab (63 mg) at weeks 12 and 16 (n=70; Group 2). The first 12 weeks of the study were placebo-controlled. Masking was maintained to week 16, and patients were followed up to week 36 [corrected]. The primary endpoint was ACR20 response at week 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267956. FINDINGS: At week 12, 32 (42%) patients in Group 1 and ten (14%) in Group 2 achieved the primary endpoint (difference 28% [95% CI 14.0-41.6]; p=0.0002). Of 124 (85%) participants with psoriasis affecting 3% or more body surface area, 33 of 63 (52%) in Group 1 and three of 55 (5%) in Group 2 had a 75% or greater improvement in psoriasis area and severity index score at week 12 (47% [33.2-60.6]; p<0.0001). During the placebo-controlled period (weeks 0-12), adverse events arose in 46 (61%) patients in Group 1 and 44 (63%) in Group 2; serious adverse events were recorded in three (4%) Group 2 patients (none in Group 1). INTERPRETATION: Ustekinumab significantly reduced signs and symptoms of psoriatic arthritis and diminished skin lesions compared with placebo, and the drug was well tolerated. Larger and longer term studies are needed to further characterise ustekinumab efficacy and safety for treatment of psoriatic arthritis.