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An investigational biologic that targets interleukin (IL)-6, olokizumab, was effective for patients with moderately to severely active rheumatoid arthritis (RA) that had been inadequately controlled with methotrexate in a phase III trial presented at the virtual meeting of the .

At week 12, a 20% improvement on the response criteria of the American College of Rheumatology (ACR20) was achieved by 63.6% of patients given subcutaneous injections of olokizumab, 64 mg every 2 weeks, and by 70.4% of those given 64 mg every 4 weeks, compared with 25.9% of those randomized to placebo (P<0.0001 for both), reported Rumen Stoilov, MD, of University Hospital St. Ivan Rilski in Sofia, Bulgaria.

IL-6 is a proinflammatory cytokine that plays numerous roles in immune function, including T cell activation and B cell proliferation. Other IL-6 inhibitors include tocilizumab (Actemra) and sarilumab (Kevzara).

Olokizumab showed efficacy in earlier phase I and II trials -- results that have now been , known as CREDO-1.

The randomized, multicenter study included 428 patients who received one of two regimens of the active treatment or placebo for 24 weeks, after which time participants were eligible for an open-label study extension.

Patents' mean age was 51, more than 80% were women, and disease duration averaged 8 years. The patients had very active disease, with C-reactive protein levels of 24 at baseline. Mean swollen and tender joint counts were 15 and 24, the Disease Activity Score in 28 joints (DAS28) was 6, and the Health Assessment Questionnaire-Disability Index (HAQ-DI) was 1.70. One third of patients were receiving glucocorticoids at baseline, and mean methotrexate dose was 16 mg/week.

"Efficacy was achieved for all classical endpoints at weeks 12 and 24 and over time," Stoilov said. At week 12, a DAS28 below 3.2, or low disease activity, was seen in 33.6% of the every-2-week group and in 38.7% of the every-4-week group compared with 3.5% of the placebo group (P<0.0001 for both).

At week 24, ACR50 responses were observed in 42.7% and 48.6% of the two olokizumab groups, respectively, compared with 7.7% of the placebo group (P<0.0001 for both), and ACR70 responses were seen in 19.6%, 22.5%, and 2.1%, respectively.

Change on the HAQ-DI was -0.54 for the every-2-week group and -0.56 for the every-4-week group and -0.20 for the placebo group.

With regard to safety, "the incidence of serious adverse events was numerically higher in the olokizumab groups than in the placebo group with no unexpected safety signals," Stoilov said.

Serious adverse events were reported in 5.6% of both active-treatment groups and in 2.8% of the placebo group. One death occurred in the every-2-week group, resulting from staphylococcal sepsis and toxic shock syndrome. There were no serious cases of herpes zoster, thromboembolism, or gastrointestinal perforation.

There also were elevations of liver enzymes and total cholesterol with olokizumab treatment. At week 24, total cholesterol levels were 5.71 mmol/L in the every-2-week group, but "levels were very close to placebo in the every-2-week group," he said -- i.e., 5.33 vs 5.23 mmol/L.

High-density lipoprotein cholesterol levels at week 24 were 167 mmol/L in the every-4-week group, 164 mmol/L in the every-2-week group, and 157 mmol/L in the placebo group.

For low-density lipoprotein cholesterol, at week 12 both active treatment groups were higher than the placebo group, at 3.22 mmol/L in the every-2-week group and 3.13 mmol/L in the every-4-week group versus 2.91 mmol/L in the placebo group, but levels declined in the every-4-week group by week 24 and was the same as in the placebo group, at 3.02 mmol/L.

Decreases in blood neutrophils also were observed in the olokizumab groups, with mean changes from baseline of -1.93 in the every-4-week group and -2.15 in the every-2-week group compared with -0.19 in the placebo group.

"In conclusion, treatment with olokizumab over a 24-week period was associated with significant improvements in the signs, symptoms, and physical function of RA, with a safety profile consistent with phase II data and the agents with similar mechanisms of action," Stoilov said. "In addition, there were no discernible differences between the two regimens of olokizumab in efficacy or safety outcomes."

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