Sirukumab dosing regimens safe, effective against DMARD-refractory RA
Use of sirukumab at 100 mg every 2 weeks and 50 mg every 4 weeks may yield significant reductions in rheumatoid arthritis (RA) symptoms, according to the SIRROUND-D study. The drug inhibits structural damage progression and improves physical function and quality of life in patients refractory to conventional disease-modifying antirheumatic drugs (DMARDs), while demonstrating an acceptable safety profile.
Results of the phase III study showed that both 100 and 50 mg regimens were superior to placebo in terms of the coprimary efficacy endpoints: proportion of patients who achieved an American College of Rheumatology 20% (ACR20) response at week 16 (53.5 and 54.8 vs 26.4 percent, respectively; p<0.001 for both) and mean change from baseline in modified Sharp/van der Heijde score (SHS) at week 52 (0.46 and 0.50 vs 3.69; p<0.001 for both). [Ann Rheum Dis 2017;doi:10.1136/annrheumdis-2017-211328]
Likewise, improvements observed in all major secondary endpoints (week 24 Health Assessment Questionnaire–Disability Index change from baseline, ACR50 response, 28-joint Disease Activity Score based on C-reactive protein, major clinical response [defined as ACR70 for 6 continuous months by week 52]) were better with both dosing regimens vs placebo (p≤0.001 for all).
The SIRROUND-D population comprised 1,670 RA patients (mean age 52.9 years; 79.9 percent female) who had moderately or severely active disease and were refractory to single-agent or combination DMARD therapy, including methotrexate or sulfasalazine. Of these, 557 were randomly assigned to the 100 mg every 2 weeks arm, 557 to the 50 mg every 4 weeks arm and 556 to the placebo arm. Sirukumab was administered subcutaneously.
“All clinical efficacy endpoints demonstrated that sirukumab was effective at reducing signs and symptoms of active RA in a robust and rapid manner through 52 weeks,” the investigators said. “Improvements occurred as early as 2 weeks in patients treated with sirukumab who demonstrated an ACR20 response; responses plateaued at week 12 and were maintained through week 52.”
Such findings were supported by the effect of structural damage inhibition at week 52, the investigators continued. Significant inhibition of radiographic progression was observed with sirukumab as early as week 24, with a significantly greater proportion of sirukumab-treated patients showing no progression at week 52 compared with those on placebo.
“Positive clinical and radiographic effects were consistently associated with significant patient-reported improvements in physical and emotional health and functional status. In a phase IIb trial and in the current phase III study, clinical efficacy was largely similar between the 100 mg every 2 weeks and 50 mg every 4 weeks sirukumab [regimens], suggesting that the two doses do not differ in their effectiveness,” the investigators pointed out. [Ann Rheum Dis 2014;73:1616–25]
In terms of safety, sirukumab did not raise any new concerns. The most frequently reported adverse events were elevated liver enzymes, upper respiratory tract infection, injection site erythema and nasopharyngitis.
Sirukumab showed a safety profile consistent with those reported for agents targeting the IL-6 receptor, such as tocilizumab and sarilumab. [J Rheumatol 2013;40:113–26; Arthritis Care Res 2014;66:1653–61; Ann Rheum Dis 2014;73:1626–34]
The investigators, however, noted that the results of the SIRROUND-D trial may not apply to the full spectrum of RA patients due the inclusion of only those who were refractory to DMARDs and who may or may not have received prior biological therapy.
Rather, the present data “provide important information on the use of anti–IL-6 therapy as a possible first-line or alternate biological therapy in patients who are no longer responding to conventional DMARDs,” they said.