medwireNews: Sirukumab, which targets the interleukin-6 cytokine, is an effective treatment for patients with rheumatoid arthritis (RA) refractory to anti-tumor necrosis factor (TNF) drugs and other biologic treatments, phase III study findings show.
Among 878 patients with active RA, the proportion achieving at least a 20% improvement in ACR criteria (ACR20) after 16 weeks was significantly greater among the 584 randomly assigned to receive sirukumab, either 50 mg every 4 weeks or 100 mg every 2 weeks, than the 294 assigned to placebo, at 40% and 45% versus 24%, respectively. The corresponding differences in the proportion of responders compared with placebo were a significant 0.16 and 0.21.
“Clinical improvements were noted as early as week 2, were sustained over time, and were associated with improvements in functioning and quality of life,” the team comments in The Lancet.
At 24 weeks, the ACR20 response rate was still significantly higher for patients taking sirukumab, at 43% for both treatment regimens compared with 26% with placebo.
Patients taking sirukumab were also significantly more likely than those taking placebo to achieve at least a 50% and 70% improvement in ACR criteria at 24 weeks, with rates of 21–22% versus 9% and 9–10% versus 4%, respectively. A significant difference in patients achieving at least a 90% improvement was seen only for those taking 100 mg of the drug every 2 weeks, at 3% versus <1% of placebo-treated patients.
“The overall responses in this study have to be interpreted in the context of this exceptionally treatment-resistant population,” Paul Tak (GlaxoSmithKline Research and Development, Stevenage, UK) and fellow researchers point out.
Eighty-eight percent of patients had discontinued previous anti-TNF treatment due to a lack of efficacy and the remainder due to intolerance or other reasons.
Most (59%) had received at least two previous biological disease-modifying antirheumatic drugs (DMARDs), including tocilizumab, and 39% had received at least two anti-TNF drugs.
Indeed, the author of a related comment described the patient population as “unusual,” adding that while the majority of patients were concomitantly taking a conventional DMARD, primarily methotrexate, 19% received sirukumab as monotherapy, despite their highly refractory status.
The researchers also note that the clinical benefits of sirukumab were accompanied by significantly greater improvements in disease activity, general physical and mental health, quality of life, and suppression of C-reactive protein and fatigue.
The incidence of adverse events was similar in the 50 and 100 mg sirukumab treatment and placebo groups, at 66%, 71% and 62%, respectively, and the rates of serious adverse events or those leading to discontinuation were comparable. Injection-site erythema was the most common adverse event overall, while infections were the most common adverse event leading to discontinuation of sirukumab at week 24, being reported in 12 patients versus one patient in the placebo group.
Five deaths occurred, all after 24 weeks, and only one of these – pneumonia – was considered possibly related to treatment.
Comparing the current findings with those of RADIATE, which assessed tocilizumab, and TARGET, which assessed sarilumab, both interleukin-6 receptor inhibitors, commentator Roy Fleischmann (University of Texas Southwestern Medical Center, Dallas, USA) says that one interpretation is that, “in a certain group of patients sirukumab might not be quite as effective as either tocilizumab or sarilumab.”
However, he concludes: “Considering the overall results of this study, the risk–benefit profile of sirukumab supports its use for the treatment of active rheumatoid arthritis in patients who are refractory to TNF inhibitors.”
By Lucy Piper
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