Promising Results With Sarilumab in Rheumatoid Arthritis

Alice Goodman

June 13, 2014

PARIS — In patients with moderate to severe rheumatoid arthritis (RA), clinical, radiographic, and functional responses were significantly better with sarilumab plus methotrexate than with methotrexate alone, new research shows.

"In this study, sarilumab showed efficacy at 2 different doses given subcutaneously every 2 weeks," said lead investigator Mark Genovese, MD, from Stanford University Medical Center in California. "Importantly, we did not see any safety issues."

"Although there is highly effective therapy for RA, many patients struggle with debilitating signs and symptoms of the disease. There is a clear need for additional treatment options," he said. "We look forward to the results of other ongoing trials in this comprehensive registration program."

SARIL-RA-MOBILITY is the first of 4 phase 3 trials of sarilumab (under development by Regeneron and Sanofi) in patients with RA. Sarilumab is an interleukin (IL)-6-receptor inhibitor, like tocilizumab, but is the first fully humanized monoclonal antibody directed against the IL-6 receptor.

The other 3 trials, evaluating a total of about 1400 patients, are currently in progress. When the final results are in, the companies plan to submit an application for approval to the US Food and Drug Administration for the treatment of RA.

Dr. Genovese presented the SARIL-RA-MOBILITY results here at the European League Against Rheumatism (EULAR) Congress 2014.

SARIL-RA-MOBILITY

The trial evaluated 1197 patients with active moderate to severe RA who had an inadequate response to methotrexate alone.

Patients from more than 200 centers in 30 countries were randomized to receive 1 of 3 treatments: sarilumab 150 mg, sarilumab 200 mg, or placebo. All treatments were given in combination with methotrexate.

The study had 3 coprimary end points: American College of Rheumatology response of at least 20% (ACR20) at week 24 indicated change in the signs and symptoms of RA; Health Assessment Questionnaire-Disability Index (HAQ-DI) score at week 16 indicated change in physical function; and van der Heijde modified total Sharp score (mTSS) at week 52 indicated change in structural damage.

For all 3 coprimary end points, the 2 doses of sarilumab were statistically superior to placebo (P < .0001 for all comparisons). The secondary end point — response of at least 70% (ACR70) for at least 24 consecutive weeks — was also better with sarilumab than with placebo.

Table 1. Outcomes

End Point Sarilumab 150 mg Group Sarilumab 200 mg Group Placebo Group
ACR20 at week 24 58% 66% 33%
HAQ-DI at week 16 –0.53 –0.55 –0.29
mTSS at week 52 0.90 0.25 2.78
ACR70 for 24 weeks 20% 25% 7%

 

The improvement in ACR20 was sustained at 52 weeks for 54% of the 150 mg group, 59% of the 200 mg group, and 32% of the placebo group.

As would be expected, adverse events were more common in the sarilumab groups than in the placebo group.

Table 2. Adverse Events

Event Sarilumab 150 mg Group Sarilumab 200 mg Group Placebo Group
Infection, % 40.1 39.6 31.1
Serious infection, % 2.6 4.0 2.3
Treatment-related discontinuation, % 12.5 13.9 4.7

 

No association was observed between serious infection and grade 3/4 neutropenia. Increases in mean low-density-lipoprotein cholesterol and liver enzymes were seen in the sarilumab-treated patients; this has been observed in previous studies of this drug.

This study is important, said EULAR president Gerd Burmester, MD, from the Charité-Universitätsmedizin in Berlin, Germany.

"It corroborates what we have found with tocilizumab, another IL-6 receptor inhibitor," he told Medscape Medical News. "We always wonder whether the effect a drug has is specific to that drug or whether it is a class effect. This study is reassuring; it supports the concept of IL-6 receptor inhibition in the treatment of rheumatoid arthritis."

The study was sponsored by Sanofi and Regeneron. Dr. Genovese reports financial relationships with Sanofi. Dr. Burmester reports financial relationships with BMS, AbbVie, Pfizer, MedImmune, MSD, Novartis, Roche, UCB, and Lilly.

European League Against Rheumatism (EULAR) Congress 2014: Abstract OP0028. Presented June 12, 2014.

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