Efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis

ObjectiveTo describe the efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) in a post-hoc analysis of randomised controlled trials.MethodsData were collected from patients in seven tofacitinib studies: six phase III (four RA, two PsA) and one phase II study (AS), and grouped into five analysis populations based on rheumatic disease diagnosis and category of prior inadequate response (IR) to treatment: conventional synthetic disease-modifying antirheumatic drugs-IR (RA and PsA), tumour necrosis factor inhibitors-IR (RA and PsA), or non-steroidal anti-inflammatory drugs-IR (AS). Only patients who received tofacitinib 5 or 10 mg twice daily or placebo were included. Pain assessments included: Patient’s Assessment of Arthritis Pain, Short-Form Health Survey 36v2 Question (Q)7 and Bodily Pain domain, Ankylosing Spondylitis Quality of Life Q9 and Q14, EuroQol Five Dimensions Pain/Discomfort dimension and Bath Ankylosing Spondylitis Disease Activity Index Q2 and Q3. Data were reported to month 6 (placebo to month 3) in the RA and PsA populations, and week 12 (tofacitinib and placebo) in the AS population.ResultsOverall, 3330 patients were included in this analysis. In the RA and PsA populations, pain improvements in tofacitinib-treated patients compared with placebo were observed at the earliest time point assessed and at month 3 (maintained to month 6). In the AS population, pain improvements compared with placebo were observed at week 12.ConclusionTofacitinib was associated with rapid and sustained improvements across multiple pain measures in patients with inflammatory rheumatic musculoskeletal diseases.

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Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-210310 ◽

2016 ◽

Vol 76 (5) ◽

pp. 840-847 ◽

Cited By ~ 112

Author(s):

Gerd R Burmester ◽

Yong Lin ◽

Rahul Patel ◽

Janet van Adelsberg ◽

Erin K Mangan ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Active Rheumatoid Arthritis ◽

Activity Index ◽

Joint Disease ◽

Phase Iii ◽

Inadequate Response ◽

Efficacy And Safety ◽

Double Blind ◽

End Point

ObjectivesTo compare efficacy and safety of sarilumab monotherapy with adalimumab monotherapy in patients with active rheumatoid arthritis (RA) who should not continue treatment with methotrexate (MTX) due to intolerance or inadequate response.MethodsMONARCH was a randomised, active-controlled, double-blind, double-dummy, phase III superiority trial. Patients received sarilumab (200 mg every 2 weeks (q2w)) or adalimumab (40 mg q2w) monotherapy for 24 weeks. The primary end point was change from baseline in 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) at week 24.ResultsSarilumab was superior to adalimumab in the primary end point of change from baseline in DAS28-ESR (−3.28 vs −2.20; p<0.0001). Sarilumab-treated patients achieved significantly higher American College of Rheumatology 20/50/70 response rates (sarilumab: 71.7%/45.7%/23.4%; adalimumab: 58.4%/29.7%/11.9%; all p≤0.0074) and had significantly greater improvement in Health Assessment Questionnaire-Disability Index (p=0.0037). Importantly, at week 24, more patients receiving sarilumab compared with adalimumab achieved Clinical Disease Activity Index remission (7.1% vs 2.7%; nominal p=0.0468) and low disease activity (41.8% vs 24.9%; nominal p=0.0005, supplemental analysis). Adverse events occurred in 63.6% (adalimumab) and 64.1% (sarilumab) of patients, the most common being neutropenia and injection site reactions (sarilumab) and headache and worsening RA (adalimumab). Incidences of infections (sarilumab: 28.8%; adalimumab: 27.7%) and serious infections (1.1%, both groups) were similar, despite neutropenia differences.ConclusionsSarilumab monotherapy demonstrated superiority to adalimumab monotherapy by improving the signs and symptoms and physical functions in patients with RA who were unable to continue MTX treatment. The safety profiles of both therapies were consistent with anticipated class effects.Trial registration numberNCT02332590.

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Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III Studies

The Journal of Rheumatology ◽

10.3899/jrheum.170486 ◽

2017 ◽

Vol 45 (2) ◽

pp. 177-187 ◽

Cited By ~ 8

Author(s):

Christina Charles-Schoeman ◽

Désirée van der Heijde ◽

Gerd R. Burmester ◽

Peter Nash ◽

Cristiano A.F. Zerbini ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Radiographic Progression ◽

Activity Index ◽

Disease Activity Index ◽

Response Rates ◽

Phase Iii ◽

Inadequate Response ◽

Link Type ◽

Phase Iii Studies

Objective.Tofacitinib has been investigated for the treatment of rheumatoid arthritis (RA) in phase III studies in which concomitant glucocorticoids (GC) were allowed. We analyzed the effect of GC use on efficacy outcomes in patients with RA receiving tofacitinib and/or methotrexate (MTX) or conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in these studies.Methods.Our posthoc analysis included data from 6 phase III studies (NCT01039688; NCT00814307; NCT00847613; NCT00853385; NCT00856544; NCT00960440). MTX-naive patients or patients with inadequate response to csDMARD or biological DMARD received tofacitinib 5 or 10 mg twice daily alone or with csDMARD, with or without concomitant GC. Patients receiving GC (≤ 10 mg/day prednisone or equivalent) before enrollment maintained a stable dose throughout. Endpoints included the American College of Rheumatology (ACR) 20/50/70 response rates, rates of Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA; CDAI ≤ 10) and remission (CDAI ≤ 2.8), and changes from baseline in CDAI, 28-joint count Disease Activity Score (DAS28-4)–erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire–Disability Index (HAQ-DI), pain visual analog scale (VAS), and modified total Sharp score.Results.Of 3200 tofacitinib-treated patients, 1258 (39.3%) received tofacitinib monotherapy and 1942 (60.7%) received tofacitinib plus csDMARD; 1767 (55.2%) received concomitant GC. ACR20/50/70 response rates, rates of CDAI LDA and remission, and improvements in CDAI, DAS28-4-ESR, HAQ-DI, and pain VAS with tofacitinib were generally similar with or without GC in monotherapy and combination therapy studies. GC use did not appear to affect radiographic progression in tofacitinib-treated MTX-naive patients. MTX plus GC appeared to inhibit radiographic progression to a numerically greater degree than MTX alone.Conclusion.Concomitant use of GC with tofacitinib did not appear to affect clinical or radiographic efficacy. MTX plus GC showed a trend to inhibit radiographic progression to a greater degree than MTX alone.

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Tofacitinib or adalimumab versus placebo: patient-reported outcomes from OPAL Broaden—a phase III study of active psoriatic arthritis in patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs

RMD Open ◽

10.1136/rmdopen-2018-000806 ◽

2019 ◽

Vol 5 (1) ◽

pp. e000806 ◽

Cited By ~ 11

Author(s):

Vibeke Strand ◽

Kurt de Vlam ◽

Jose A Covarrubias-Cobos ◽

Philip J Mease ◽

Dafna D Gladman ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Patient Reported Outcomes ◽

Short Form ◽

Janus Kinase ◽

Phase Iii ◽

Placebo Patient ◽

Pain Patient ◽

Inadequate Response ◽

Patient Reported ◽

Disease Modifying

ObjectivesTofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). We evaluated patient-reported outcomes (PROs) in patients with PsA refractory to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and tumour necrosis factor inhibitor-naïve in a 12-month, phase III randomised controlled trial (OPAL Broaden [NCT01877668]).MethodsPatients (N=422) received tofacitinib 5 mg or 10 mg twice daily, adalimumab 40 mg subcutaneously every 2 weeks or placebo advancing to tofacitinib 5 mg or 10 mg twice daily at month 3. Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences (MCID); and scores ≥normative values in: Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level questionnaire (EQ-5D-3L) and Ankylosing Spondylitis Quality of Life (ASQoL) were determined. Nominal p values were cited without multiple comparison adjustments.ResultsAt month 3, PtGA, Pain, PGJS, FACIT-Fatigue, EQ-5D-3L, ASQoL and SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP) and vitality domain scores exceeded placebo with both tofacitinib doses (p≤0.05); SF-36v2 social functioning with 5 mg twice daily (p≤0.05). Percentages reporting improvements ≥MCID in PtGA, Pain, PGJS, FACIT-Fatigue, ASQoL and SF-36v2 PCS, PF, BP and general health scores exceeded placebo with both tofacitinib doses (p≤0.05) and were similar with adalimumab.ConclusioncsDMARD-IR patients with active PsA reported statistically and clinically meaningful improvements in PROs with tofacitinib compared with placebo at Month 3.

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Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-209068 ◽

2016 ◽

Vol 75 (11) ◽

pp. 1984-1988 ◽

Cited By ~ 80

Author(s):

Arthur Kavanaugh ◽

Lluis Puig ◽

Alice B Gottlieb ◽

Christopher Ritchlin ◽

Yin You ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Disease Activity ◽

Activity Index ◽

Phase Iii ◽

Efficacy And Safety ◽

Peripheral Arthritis ◽

Link Type ◽

Study Results ◽

Post Hoc

ObjectiveTo evaluate ustekinumab efficacy and safety in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (termed the ‘spondylitis subset’).MethodsAdults with active PsA (PSUMMIT-1/PSUMMIT-2, n=615/312) were randomised to ustekinumab 45 mg, 90 mg or placebo at week 0/week 4/q12 week. At week 16, patients with <5% improvement in tender and swollen joints entered blinded early escape. A subset of patients with physician-identified spondylitis was evaluated with spondylitis-specific assessments, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score employing C reactive protein (ASDAS-CRP), through week 24.Results256/927 (27.6%) PSUMMIT-1/PSUMMIT-2 patients (placebo/ustekinumab, n=92/164) comprised the evaluable spondylitis subset. At week 24, in this analysis subset, significantly more patients achieved BASDAI20/50/70 responses (54.8%/29.3%/15.3% vs 32.9%/11.4%/0%; p≤0.002), improvement in BASDAI question 2 concerning axial pain (1.85 vs 0.24; p<0.001) and mean per cent ASDAS-CRP improvements (27.8% vs 3.9%; p<0.001) for ustekinumab versus placebo recipients, respectively. Comparable to the overall study population, significant improvements were also achieved in psoriasis, peripheral arthritis, enthesitis, dactylitis, physical function and peripheral joint radiographs in the spondylitis subset.ConclusionsIn this post-hoc analysis of PsA patients with baseline peripheral arthritis and physician-reported spondylitis, ustekinumab-treated patients demonstrated significant improvements in axial signs and symptoms through week 24.Trial registration numberPSUMMIT-1 (NCT01009086, EudraCT 2009-012264-14) and PSUMMIT-2 (NCT01077362, EudraCT 2009-012265-60); post-study results.

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Therapy-related issues: musculoskeletal

10.1093/med/9780198735823.003.0024 ◽

2017 ◽

Author(s):

Philip Wiffen ◽

Marc Mitchell ◽

Melanie Snelling ◽

Nicola Stoner

Keyword(s):

Rheumatoid Arthritis ◽

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Musculoskeletal Diseases ◽

British National Formulary ◽

National Formulary ◽

Clinical Pharmacists

This chapter outlines information relevant to clinical pharmacists related to musculoskeletal diseases and is loosely based on the British National Formulary, Chapter 10. In particular, this chapter covers rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, osteoarthritis, osteoporosis, and gout.

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Patient-reported Outcome in Psoriatic Arthritis: A Comparison of Web-based Versus Paper-completed Questionnaires

The Journal of Rheumatology ◽

10.3899/jrheum.110165 ◽

2011 ◽

Vol 38 (12) ◽

pp. 2619-2624 ◽

Cited By ~ 21

Author(s):

HEATHER MacKENZIE ◽

ARANE THAVANESWARAN ◽

VINOD CHANDRAN ◽

DAFNA D. GLADMAN

Keyword(s):

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Activity Index ◽

Short Form ◽

Life Quality ◽

Correlation Coefficients ◽

Disease Activity Index ◽

The Other ◽

Web Based ◽

Patient Reported

Objective.Patients followed in observational cohorts often complete patient-reported outcomes on paper questionnaires. With advances in technology, Web-based (WB) formats have been developed. The aims of our study were to determine whether WB and paper-based questionnaires (PB) completed by patients followed in the psoriatic arthritis (PsA) clinic are comparable; whether there is a patient preference for one method or the other; and whether any preference is related to patient characteristics.Methods.Consecutive patients followed at the PsA clinic completed the Health Assessment Questionnaire, Medical Outcomes Study Short Form-36, fatigue scale, Dermatology Life Quality Index, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life Instrument, and EQ-5D both on paper (PB) and on computer by Internet (WB). Patients were also asked to complete questionnaires regarding their preference for one method or the other. Descriptive statistics and interclass correlation coefficients (ICC) were calculated.Results.Of 110 patients who agreed to participate, 67 (57.3%) successfully completed both PB and WB questionnaires. These patients did not differ from those who did not complete the questionnaires. WB and PB questionnaires took the same length of time to complete, with 20% of the patients complaining of more pain following completion of the questionnaires, more so with the PB. There was excellent agreement between the PB and WB (ICC 0.89–0.97) for all questionnaires.Conclusion.The PB and WB versions of 10 standardized self-administered questionnaires in patients with PsA were comparable. The WB format was well accepted by PsA outpatients. Patients may thus be offered a choice of format as well as the choice to complete the questionnaires either in the clinic or remotely by Internet.

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Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-209821 ◽

2016 ◽

Vol 76 (4) ◽

pp. 694-700 ◽

Cited By ~ 35

Author(s):

Josef S Smolen ◽

Joel M Kremer ◽

Carol L Gaich ◽

Amy M DeLozier ◽

Douglas E Schlichting ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Patient Reported Outcomes ◽

Short Form ◽

Analysis Of Covariance ◽

Phase Iii ◽

Inadequate Response ◽

Continuous Variables ◽

Activity Impairment ◽

Patient Reported ◽

Phase Iii Study

ObjectivesTo assess baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis, who had insufficient response or intolerance to ≥1 tumour necrosis factor inhibitors (TNFis) or other biological disease-modifying antirheumatic drugs (bDMARDs).MethodsIn this double-blind phase III study, patients were randomised to once-daily placebo or baricitinib 2 or 4 mg for 24 weeks. PROs included the Short Form-36, EuroQol 5-D, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain, duration of morning joint stiffness (MJS) and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis. Treatment comparisons were performed with logistic regression for categorical measures or analysis of covariance for continuous variables.Results527 patients were randomised (placebo, 176; baricitinib 2 mg, 174; baricitinib 4 mg, 177). Both baricitinib-treated groups showed statistically significant improvements versus placebo in most PROs. Improvements were generally more rapid and of greater magnitude for patients receiving baricitinib 4 mg than 2 mg and were maintained to week 24. At week 24, more baricitinib-treated patients versus placebo-treated patients reported normal physical functioning (HAQ-DI <0.5; p≤0.001), reductions in fatigue (FACIT-F ≥3.56; p≤0.05), improvements in PtGA (p≤0.001) and pain (p≤0.001) and reductions in duration of MJS (p<0.01).ConclusionsBaricitinib improved most PROs through 24 weeks compared with placebo in this study of treatment-refractory patients with previously inadequate responses to bDMARDs, including at least one TNFi. PRO results aligned with clinical efficacy data for baricitinib.Trial registration numberNCT01721044; Results.

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