Filgotinib scores in RA patients with limited or no MTX exposure

The Janus kinase (JAK)-1 inhibitor filgotinib delivers meaningful benefits for signs and symptoms of rheumatoid arthritis (RA), as well as physical function, in patients with limited or no prior exposure to methotrexate (MTX), according to the results of the phase III FINCH 3 trial.

“These effects were sustained through 52 weeks,” the investigators said. “Both filgotinib doses [tested in the trial] were well tolerated with an acceptable safety profile.”

FINCH 3 included 1,249 adult RA patients (mean age, 53 years; 77 percent female) with previous MTX exposure of <3 doses ≤25 mg or none at all, ≥6 swollen joint count of 66 joints (SJC66), and ≥6 tender joints of 68 joints (TJC68) at screening. They were randomized to receive filgotinib 200 mg with MTX (FIL200+MTX; n=416), filgotinib 100 mg with MTX (FIL100+MTX; n=207), filgotinib 200 mg monotherapy (FIL200; n=210), or MTX alone (n=416).

The study drug was administered orally once daily, while MTX was given orally once weekly, starting with 10 mg/week and escalating to 15 mg at week 4 and 20 mg at week 8. Patients without 20-percent improvement in SJC66 and TJC68 at week 24, or after two consecutive visits from weeks 30 through 52, discontinued filgotinib and received standard of care. 

Most of the patients completed study drug through weeks 24 (90.5 percent) and 52 (82 percent). The primary endpoint of a 20-percent improvement in American College of Rheumatology criteria (ACR20) at week 24 occurred more frequently with FIL200+MTX and FIL100+MTX than with MTX alone (81 percent and 80 percent vs 71 percent; p<0.001 and p=0.017, respectively). [Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2020-219213]

“The proportion of patients achieving ACR20 at week 24 [on] FIL200 monotherapy did not attain statistical significance versus MTX in the hierarchical testing scheme,” the investigators noted.

There was a parallel improvement seen in functional status. Health Assessment Questionnaire-Disability Index decreased from baseline by −1.0 with FIL200+MTX and −0.94 with FIL100+MTX, which were significantly greater compared with the change of −0.81 achieved with MTX (p<0.001 and p=0.008, respectively).

Both combination regimens led to significantly higher proportions of patients achieving 28-joint Disease Activity Score (DAS28) based on CRP <2.6 (54 percent with FIL200+MTX and 43 percent with FIL100+MTX vs 29 percent with MTX; p<0.001 for both).

Furthermore, more patients on any filgotinib regimen showed no radiographic progression (modified total Sharp/van der Heijde score [mTSS] ≤0) compared with those on MTX. Week 52 results for mTSS were 0.21 with FIL200+MTX, 0.27 with FIL100+MTX, and 0.23 with FIL200 versus 0.74 with MTX.

Over 52 weeks, adverse event (AE) rates were similar across treatment arms. There were no significant differences in serious AEs, serious infections, opportunistic infections, herpes zoster, major adverse cardiovascular events, and malignancies. Among patients who received filgotinib, none developed venous thromboembolism while four died. All deaths were consistent with common causes of mortality in RA except for lupus myocardiopathy.

“Given the high-hurdle outcomes at week 52, an initial dose of filgotinib 200 mg eventually tapering to 100 mg in patients with good disease control at 1 year may be considered in clinical practice,” the investigators said.

“An additional study evaluating early, temporary use of JAK inhibitors or biological disease-modifying antirheumatic drugs in patients with a suboptimal early response to initial MTX and tapering glucocorticoids is needed to assess potential benefits of this strategy,” they added.

Finally, the investigators acknowledged that the findings have limited generalizability, pointing out that 34 percent of the study population had disease duration >1 year with no prior DMARD therapy, which goes against the current recommendation of early initiation of DMARDs after RA diagnosis.

“However, in sensitivity analyses in which patients were stratified by disease duration of <1 or >1 year, results were similar regardless of disease duration for all endpoints evaluated,” they said.