Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2)

Ann Rheum Dis. 2017 Jun;76(6):1009-1019. doi: 10.1136/annrheumdis-2016-210105. Epub 2016 Dec 19.

Abstract

Objectives: To evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX).

Methods: In this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12.

Results: Overall, 283 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib at any dose achieved ACR20 responses versus placebo (≥65% vs 29%, p<0.001). For other key end points at week 12 (ACR50, ACR70, ACR-N, Disease Activity Score based on 28 joints and C reactive protein, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index) significant differences from baseline in favour of filgotinib 100 and 200 mg versus placebo were seen; responses were maintained or improved through week 24. Rapid onset of action was observed for most efficacy end points. Dose-dependent increases in haemoglobin were observed. The percentage of patients with treatment-emergent adverse events (TEAE) was similar in the placebo and filgotinib groups (∼40%). Eight patients on filgotinib and one on placebo had a serious TEAE, and four patients, all of whom received filgotinib, experienced a serious infection. No tuberculosis or opportunistic infections were reported.

Conclusions: Over 24 weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action. Filgotinib was generally well tolerated.

Trial registration number: NCT01894516.

Keywords: DAS28; Rheumatoid Arthritis; Treatment.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • C-Reactive Protein / metabolism
  • Disability Evaluation
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Hemoglobins / metabolism
  • Humans
  • Infections / chemically induced
  • Janus Kinase 1 / antagonists & inhibitors
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Retreatment
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Treatment Outcome
  • Triazoles / administration & dosage*
  • Triazoles / adverse effects

Substances

  • Antirheumatic Agents
  • GLPG0634
  • Hemoglobins
  • Protein Kinase Inhibitors
  • Pyridines
  • Triazoles
  • C-Reactive Protein
  • Janus Kinase 1
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT01894516