Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate: Results of a phase II, randomized, placebo-controlled trial

ObjectiveTo provide the first direct comparison of patient-reported outcomes (PROs) following treatment with tofacitinib monotherapy versus tofacitinib or adalimumab (ADA) in combination with methotrexate (MTX) in patients with rheumatoid arthritis (RA) with inadequate response to MTX (MTX-IR).MethodsORAL Strategy (NCT02187055), a phase IIIB/IV, head-to-head, randomised controlled trial, assessed non-inferiority between tofacitinib 5 mg two times per day monotherapy, tofacitinib 5 mg two times per day+MTX and ADA 40 mg every other week+MTX. PROs assessed included the following: Patient Global Assessment of disease activity (PtGA), Pain, Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue and 36-Item Short-Form Health Survey (SF-36) summary and domain scores.ResultsSubstantial improvements from baseline were reported across all PROs in all treatment arms, which, in the majority, met or exceeded minimum clinically important differences. Compared with tofacitinib monotherapy, tofacitinib+MTX combination treatment conferred significantly greater improvements in PtGA, Pain and SF-36 physical component summary scores at month 6. Statistically or numerically greater improvements were often, but not uniformly, reported for combination treatments compared with tofacitinib monotherapy at other time points.ConclusionTreatment with tofacitinib+MTX, ADA+MTX and tofacitinib monotherapy resulted in clinically meaningful improvements in PROs in MTX-IR patients with RA. These were comparatively greater with combination treatments versus tofacitinib monotherapy, although differences between treatment arms were small, limiting our ability to confer clinical meaning.Trial registration numberNCT02187055.

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Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase IIb, randomised, placebo-controlled trial

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-212478 ◽

2018 ◽

Vol 77 (4) ◽

pp. 495-499 ◽

Cited By ~ 2

Author(s):

Ronald F van Vollenhoven ◽

Edward Clark Keystone ◽

Vibeke Strand ◽

Cesar Pacheco-Tena ◽

Jiří Vencovský ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Biological Activity ◽

Active Rheumatoid Arthritis ◽

Controlled Trial ◽

Inadequate Response ◽

Acr20 Response ◽

American College Of Rheumatology ◽

Registration Number ◽

Dose Dependent ◽

Acr20 Response Rate

ObjectiveTo evaluate the efficacy, biological activity and safety of tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX).Methods321 patients were randomised (1:1:1:1) to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in addition to MTX treatment. Responders at week 12 continued the same treatment, and non-responders at week 12 were escalated to the next higher tregalizumab dose level or re-randomised from placebo to active treatment. After 24 weeks, patients could continue treatment with tregalizumab for 24 weeks (extension phase). The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Safety and biological activity were monitored through week 48.ResultsAt week 12, ACR20 response rates were not statistically significantly different between placebo and any of the tregalizumab doses. Tregalizumab injections were well tolerated; most adverse events were mild to moderate and comparable among treatment and placebo groups. Biological activity was shown by dose-dependent CD4 downmodulation.ConclusionTreatment with tregalizumab did not show significant clinical efficacy in patients with active RA compared with placebo but resulted in the expected biological effect on CD4 modulation. Tregalizumab was generally well tolerated, and no new safety findings were identified.Trial registration numberNCT01999192; Results.

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Efficacy, safety, pharmacokinetics and immunogenicity of abatacept administered subcutaneously or intravenously in Japanese patients with rheumatoid arthritis and inadequate response to methotrexate: a Phase II/III, randomized study

Modern Rheumatology ◽

10.3109/14397595.2014.881954 ◽

2014 ◽

Vol 24 (6) ◽

pp. 885-891 ◽

Cited By ~ 11

Author(s):

Mitsuhiro Iwahashi ◽

Hiroshi Inoue ◽

Tsukasa Matsubara ◽

Takaaki Tanaka ◽

Koichi Amano ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Phase Ii ◽

Randomized Study ◽

Japanese Patients ◽

Inadequate Response

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Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial

Annals of the Rheumatic Diseases ◽

10.1136/ard.2009.108159 ◽

2009 ◽

Vol 69 (2) ◽

pp. 413-416 ◽

Cited By ~ 103

Author(s):

J H Coombs ◽

B J Bloom ◽

F C Breedveld ◽

M P Fletcher ◽

D Gruben ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Health Status ◽

Short Form ◽

Controlled Trial ◽

Health Assessment ◽

Janus Kinase ◽

Inadequate Response ◽

Double Blind ◽

Sf 36 ◽

Factor Α

Objectives:To determine the efficacy of CP-690,550 in improving pain, function and health status in patients with moderate to severe active rheumatoid arthritis (RA) and an inadequate response to methotrexate or a tumour necrosis factor α inhibitor.Methods:Patients were randomised equally to placebo, CP-690,550 5, 15 or 30 mg twice daily for 6 weeks, with 6 weeks’ follow-up. The patient’s assessment of arthritis pain (pain), patient’s assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 (SF-36) were recorded.Results:At week 6, significantly more patients in the CP-690,550 5, 15 and 30 mg twice-daily groups experienced a 50% improvement in pain compared with placebo (44%, 66%, 78% and 14%, respectively), clinically meaningful reductions in HAQ-DI (⩾0.3 units) (57%, 75%, 76% and 36%, respectively) and clinically meaningful improvements in SF-36 domains and physical and mental components.Conclusions:CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.

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