Pam Harrison

November 14, 2015

Filgotinib is safe and effective for patients with rheumatoid arthritis who have an inadequate response to methotrexate therapy, according to results from the phase 2b DARWIN 1 study.

"We saw a significant improvement in the signs and symptoms of rheumatoid arthritis with filgotinib," said René Westhovens, MD, PhD, from the Department of Rheumatology at the Catholic University of Leuven in Belgium. In addition, there was no difference in serious adverse effects between the selective Janus kinase 1 inhibitor filgotinib and placebo.

"These robust data should lead to further phase 2 investigations in the development of filgotinib for the treatment of rheumatoid arthritis," he said.

Dr Westhovens presented the DARWIN 1 results at the American College of Rheumatology (ACR) 2015 Annual Meeting in San Francisco.

The study involved patients with rheumatoid arthritis who had been receiving a stable dose of methotrexate of approximately 16 mg/week for a mean duration of 8 to 9 years. About two thirds of the patients were also receiving corticosteroids. At baseline, Disease Activity Score in 28 joints (DAS28) using C-reactive protein (CRP) ranged from 6.0 to 6.2.

The 594 patients involved were randomly assigned in equal numbers to placebo or one of six doses of filgotinib: 25 mg twice daily, 50 mg once daily, 50 mg twice daily, 100 mg once daily, 100 mg twice daily, or 200 mg once daily. All patients continued receiving methotrexate.

The primary end point was a 20% improvement in ACR criteria (ACR20), but the investigators also looked at ACR50 and the effect of treatment on the DAS28-CRP.

At 12 weeks, the ACR20 response was significantly better with 100 mg twice daily (P < .001) and with 200 mg once daily (P < .05) than with placebo.

"Achieving an ACR20 response was also very rapid. It occurred within the first 2 weeks," Dr Westhovens reported.

Table. Outcomes

Regimen ACR20 Response at 12 Weeks, % Remission at 24 Weeks, % Low Disease Activity at 24 Weeks, %
Placebo 44 9 19
Twice-daily filgotinib      
 25 mg 57 23 40
 50 mg 60 24 38
 100 mg 79 40 64
Once-daily filgotinib      
 50 mg 56 21 33
 100 mg 64 36 51
 200 mg 69 26 51

At week 12, the ACR50 response was better with any dose of filgotinib than with placebo, and the difference between filgotinib-treated patients and placebo-treated patients was significant. In fact, the ACR50 response was 43% better with 100 mg twice daily than with placebo (P < .001), and 55% better with 200 mg once daily than with placebo (P < .001).

At week 25, ACR20 rates were 75% to 80%, and there was a nice dose–response curve for the different filgotinib doses, Dr Westhovens reported.

By the end of the study, at least half of the filgotinib-treated patients achieved an ACR50 response, and 35% to 40% of filgotinib-treated patients achieved an ACR70 response. This "is also impressive," he added.

The mean decrease from baseline in the DAS28-CRP score ranged from a high of 2.8 with a 200-mg once-daily dose to a low of 1.8 with a 50-mg once-daily dose. In the placebo group, the mean decrease was 1.2.

At week 24, remission rates and levels of disease activity were also better in filgotinib-treated patients than in placebo-treated patients.

Adverse Events

Rates of serious adverse events were similar in filgotinib-treated and placebo-treated patients (5% vs 7%).

With filgotinib, "there was an increase in neutrophils in the first 4 weeks, after which levels stabilized. There was an initial bump in lymphocytes as well, which again stabilized over time," Dr Westhovens said.

In addition, "hemoglobin increased over the 6 months of follow-up, and high-density lipoprotein increased more than low-density lipoprotein over time as well," he reported.

 
The promise of filgotinib, based on what we've seen in this study, is high. These are impressive data. Dr Peter Taylor
 

Physicians will have to wait for a phase 3 trial to determine the potential positioning of filgotinib if it is approved for the treatment of rheumatoid arthritis, said session moderator Peter Taylor, PhD, professor of musculoskeletal sciences at the University of Oxford in the United Kingdom.

"We don't know this yet," said Dr Taylor, "but the promise of filgotinib based on what we've seen in this study is high. These are impressive data."

Dr Westhovens reports financial interests with Roche Pharmaceuticals, Bristol-Myers Squibb, Janssen, and Galapagos. Dr Taylor reports serving as a consultant for Galapagos, Lilly, and Pfizer.

American College of Rheumatology (ACR) 2015 Annual Meeting: Abstract 1048. Presented November 8, 2015.

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