Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes.

Abstract

BACKGROUND:

The aim was to assess patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) treated with filgotinib during two phase 2b, 24-week, randomized, placebo-controlled studies.

METHODS:

Patients with moderate-to-severe active RA and an inadequate response to methotrexate (MTX) were randomized to daily placebo or filgotinib 50 mg, 100 mg, or 200 mg as add-on therapy to MTX (NCT01888874) or as monotherapy (NCT01894516). At week 12, nonresponders receiving filgotinib 50 mg in both studies or placebo in the add-on study, and all patients receiving placebo as monotherapy, were re-assigned to filgotinib 100 mg. PROs were measured using the Health Assessment Questionnaire - Disability Index (HAQ-DI) including Patient Pain assessed by visual analog scale, and the Patient Global Assessment of Disease Activity (Patient Global), the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale (Version 4), and the 36-Item Short Form Health Survey (SF-36).

RESULTS:

At week 12, improvements in all PROs, apart from the SF-36 mental component in the add-on study, were statistically better with filgotinib than placebo; some improvements were noted as early as the first assessment time point (week 1 or week 4). Filgotinib improved HAQ-DI by 0.58-0.84 points, FACIT-Fatigue by 6.9-11.4 points, Patient Global by 25.2-35.6 mm, and Pain by 24.2-37.9 mm; scores were maintained or improved to week 24. Across all PROs, more patients achieved minimal clinically important differences and normative values with filgotinib 200 mg than placebo. Patients re-assigned to filgotinib 100 mg at week 12 experienced improvements in PROs between weeks 12 to 24.

CONCLUSIONS:

Filgotinib as MTX add-on therapy or as monotherapy demonstrated rapid and sustained (to 24 weeks) improvements in health-related quality of life and functional status in patients with active RA.

TRIAL REGISTRATION:

MTX add-on study: ClinicalTrials.gov , NCT01888874 . Registered on 28 June 2013. Monotherapy study: ClinicalTrials.gov , NCT01894516 . Registered on 10 July 2013.

• Authors: Mark Genovese, Rene Westhovens, Luc Meuleners, Annegret Van der Aa, Pille Harrison, Chantal Tasset, Arthur Kavanaugh
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 20 Issue 1 Pg. 57 (03 23 2018) ISSN: 1478-6362 [Electronic] England
• PMID: 29566740 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• GLPG0634
• Protein Kinase Inhibitors
• Pyridines
• Triazoles
• Janus Kinase 1
• Methotrexate

Topics

• Antirheumatic Agents (administration & dosage)
• Arthritis, Rheumatoid (diagnosis, drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Janus Kinase 1 (antagonists & inhibitors, metabolism)
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Patient Reported Outcome Measures
• Protein Kinase Inhibitors (administration & dosage)
• Pyridines (administration & dosage)
• Treatment Outcome
• Triazoles (administration & dosage)