Olokizumab excels in rheumatoid arthritis uncontrolled with MTX

The investigational interleukin (IL)-6 inhibitor olokizumab is effective in improving symptoms and physical function of patients with moderate-to-severe rheumatoid arthritis (RA) who are inadequately controlled with methotrexate (MTX), according to the CREDO-1 study presented at the EULAR 2020 Virtual Meeting.

At week 12, the primary outcome of ACR20* response was achieved by significantly more patients treated with olokizumab than placebo (63.6 percent and 70.4 percent vs 25.9 percent for olokizumab 64 mg Q2W and Q4W vs placebo, respectively; p<0.0001 for both). [EULAR 2020, abstract OP0021]

Also, more patients in both the olokizumab arms attained low disease activity at week 12 (defined as DAS28** <3.2) compared with the placebo arm (33.6 percent and 38.7 percent vs 3.5 percent, respectively; p<0.0001 for both).  

“Efficacy was achieved for all classical endpoints at weeks 12 and 24 and over time,” reported Dr Rumen Stoilov of University Hospital St. Ivan Rilski in Sofia, Bulgaria.

At week 24, ACR50 responder rates were also significantly greater with both olokizumab regimens than with placebo (42.7 percent and 48.6 percent vs 7.7 percent; p<0.0001 for both). Similarly, ACR70 response rates were higher in olokizumab-treated patients than those on placebo (19.6 percent and 22.5 percent vs 2.1 percent, respectively).

In addition, physical function measured on the HAQ-DI*** showed greater improvements from baseline in both the olokizumab arms vs the placebo arm at week 12 (least-squares mean change, -0.54 and -0.56 vs -0.20, respectively; p<0.0001 for both).

“Both regimens of olokizumab were significantly better than placebo in all primary and secondary endpoints,” Stoilov said. “Improvements in efficacy outcomes became evident after 4 to 8 weeks from olokizumab initiation and were maintained throughout the 24-week period.”

The double-blind, multicentre, phase III study involved 428 patients (mean age 52.3 years, 82.7 percent female) with moderately to severely active RA despite MTX treatment. They were randomized 1:1:1 to receive subcutaneous olokizumab 64 mg Q2W or Q4W or placebo for 24 weeks. From week 14 onwards, rescue medications were allowed for nonresponders. After week 24, participants were eligible to enter an open-label extension study.

Overall, treatment-emergent adverse events (TEAEs) occurred in 58.0 percent, 57.0 percent, and 43.7 percent of patients receiving olokizumab Q2W, Q4W, and placebo, respectively. Serious AEs were seen in 5.6 percent of patients in both olokizumab arms compared with 2.8 percent in the placebo arm. There were no serious events of thromboembolism, herpes zoster, or gastrointestinal perforation.

Decreases in blood neutrophils occurred predominantly in the olokizumab arms (mean change from baseline, -2.15 and -1.93 vs -0.19, respectively). Elevations of total cholesterol levels and liver enzymes were also seen with olokizumab treatment.

According to Stoilov, “Safety profile was consistent with phase II data and with the other agents with similar mechanism of action.”

“There were no discernible differences between the two regimens of olokizumab in efficacy or safety outcomes,” he added.