IL-6 receptor antibody efficacious for rheumatoid arthritis nonresponsive to methotrexate
Vobarilizumab, a nanobody consisting of an anti-interleukin 6 (IL-6) receptor domain developed for the treatment of rheumatoid arthritis (RA), is shown to be safe and efficacious in RA patients with inadequate response to methotrexate in a study presented at the European League Against Rheumatism (EULAR) Annual Congress 2017 held recently in Madrid, Spain.
At the 24th week of this double-blind, placebo-controlled trial of 345 patients, higher remission rates were found in patients who received vobarilizumab vs placebo (19–20 percent vs 9–10 percent). [EULAR 2017, abstract OP0098]
“Vobarilizumab is a bispecific nanobody bound to human serum albumin for half-life extension. It has no Fc portion, which eliminates the possibility of antibody-dependent cell cytotoxicity,” said study author Professor Thomas Dörner of the Rheumatology and Clinical immunology, Charité University Hospitals, Berlin, Germany.
Patients included in the study had already been receiving methotrexate (average dose, 17 mg/week) and were assigned to receive either placebo or one of four different doses of vobirilizumab (75 mg or 150 mg every 4 weeks, or 150 mg or 225 mg every 2 weeks).
At week 24, more patients treated with vobarilizumab achieved ACR50 (American College of Rheumatology 50 percent improvement) and ACR 70 responses vs placebo. Rates of ACR50 were up to 61 percent with vobarilizumab vs 39 percent with placebo, while rates of ACR70 were up to 45 percent vs 17 percent.
The proportion of patients who sustained ACR50 and ACR70 responses was noted to be higher in the vobarilizumab vs placebo group (ACR50, 29–39 percent vs 16 percent; ACR70, 11–13 percent vs 4 percent).
Moreover, a higher proportion of vobarilizumab-treated patients achieved low disease activity as measured by DAS28-CRP (Disease Activity Score 28-C reactive protein) (39–51 percent vs 16 percent with placebo).
Vobarilizumab also exhibited a favourable safety profile through week 24 and subsequent follow-up periods. The frequency of any treatment-emergent adverse event (TEAE) was similar among all treatment groups (52–65 percent).
“Our study showed that in patients with RA not responsive to methotrexate, treatment with vobarilizumab, a newly developed IL-6R antibody, has a positive impact on efficacy endpoints. ACR responses and low disease activity were maintained in a substantial proportion of patients,” Dörner concluded.
In a similar investigation also presented at EULAR Annual Congress 2017, the study group found that in 251 RA patients, vobarilizumab monotherapy had similar efficacy in terms of ACR20 at week 12 vs tocilizumab (up to 81 percent vs 78 percent). The rate of TEAEs was also similar across the vobarilizumab and tocilizumab groups. [EULAR 2017, abstract FRI0239]