Filgotinib promising in RA patients naïve to methotrexate

The selective Janus kinase (JAK)1 inhibitor filgotinib induced clinically meaningful responses with high patient rates achieving the study endpoint [1].

Filgotinib, the orally administered, selective inhibitor of JAK1 has shown good efficacy and was well tolerated for the treatment of rheumatoid arthritis (RA) in phase 2 and 3 studies evaluating patients with prior inadequate response to biologics or as add-on to methotrexate [2,3].

The phase 3 FINCH 3 trial, conducted by Prof. Rene Westhovens (University of Leuven, Belgium) and his colleagues, now investigated efficacy and safety of filgotinib as monotherapy or in combination with methotrexate in methotrexate-naïve RA patients. At screening, patients had an ACR functional class 1-3, swollen joint count in 66 joints (SJC66) ≥6, and 68‐joint tender joint count (TJC68) ≥6. A total of 1,249 randomised patients received one of the study drug regimens: group A, filgotinib 200 mg plus methotrexate; group B, filgotinib 100 mg plus methotrexate; group C, monotherapy with filgotinib 200 mg; and group D, monotherapy with methotrexate. Primary outcome was the proportion of patients reaching an ACR20 response at week 24. In addition, secondary outcomes such as ACR70 response, Disease Activity Score 28/C-reactive protein (DAS28-CRP) ≤3.2 and <2.6, and van der Heijde modified Total Sharp Score (mTSS) were evaluated. At baseline, most patients (76.9%) were female and 35.9% were treated with corticosteroids. At this point, RA was diagnosed 2.2 years earlier (mean value) and the mean DAS28-CRP was 5.7.

At week 24, significantly more patients in group A (81%, P<0.001) and group B (80.2%, P<0.05) achieved ACR20 response, compared with those using monotherapy with methotrexate (71.4%; see Figure). ACR20 was observed in 78.1% receiving monotherapy with filgotinib. ACR70 rates for arms A-D were 43.8%, 40.1%, 40.0%, and 26.0%. All filgotinib arms attained DAS28-CRP <3.2 in 60% of patients or more, while with methotrexate monotherapy this was reached only by 46.2% of patients. In addition, both filgotinib combination arms (groups A and B) slowed radiographic progression compared with methotrexate monotherapy (P<0.01 for both comparisons). All filgotinib arms were significantly superior to methotrexate with regard to physical function. A clinically meaningful response to filgotinib occurred as early as 2 weeks after treatment initiation. A higher proportion of patients receiving filgotinib either alone or in combination with methotrexate achieved clinical remission.

Figure: Primary outcome of the FINCH 3 trial: ACR20 response at week 24 [1]

Filgotinib alone or in combination with methotrexate was well tolerated. Any kind of treatment-emergent adverse event was seen in 65.9% (group A), 69.6% (group B), 53.8% (group C), and 62.7% (group D) of patients. Among them, serious adverse events occurred in 4.1% (group A), 2.4% (group B), 4.8% (group C), and 2.9% (group D); rates for serious infections were 1.0%, 1.0%, 1.4%, and 1.0% respectively.

1. 
   
   1.  Westhovens R et al. Abstract 927. ACR 2019, 9-13 November, Atlanta (GA/USA).
   2. Genovese M, et al. JAMA 2019;322:315-325.
   3. Westhovens R, et al. Ann Rheum Dis 2017;76:998-1008.

 



Posted on 4 February 202016 February 2024