The approved IL-6 receptor antagonist’s tocilizumab and sarilumab have demonstrated substantial improvements in clinical outcomes for rheumatoid arthritis. Tocilizumab's favorable balance of efficacy and safety has spurred the rapid development of biosimilars and novel potent IL-6 receptor inhibitors. R-Pharm’s olokizumab has shown promising efficacy in Phase III trials and its safety profile in open-label extensions, suggesting that direct IL-6 inhibitors could play a significant role alongside existing treatments in managing this condition. 

In a study involving 110 rheumatoid arthritis patients the efficacy and safety of transitioning from IL-6 receptor inhibitors (IL-6R) to olokizumab were evaluated. The mean duration of rheumatoid arthritis was 13.1 years, and patients had been on IL-6R inhibitors for approximately 47.8 months before switching to olokizumab, primarily due to IL-6R inhibitor unavailability.

After switching to olokizumab (64mg q4w SC), 97.3% of patients remained on therapy at 6 months, decreasing slightly to 88.2% at 12 months. Significant clinical improvement was observed, with 74.8% and 84.0% achieving remission or low disease activity according to DAS28-CRP scores at 6 and 12 months, respectively. Similar results were seen with DAS28-ESR scores (70.5% at 6 months and 81.0% at 12 months).

Patients who switched to olokizumab within 40 days after their last IL-6R administration (n=60) showed stable disease activity by the 6 and 12 months on therapy, with DAS28-CRP scores of 2.5 and 2.2, and DAS28-ESR scores of 2.4 and 2.1, respectively. In contrast, patients switching more than 40 days after their last IL-6R administration (n=50) experienced increased disease activity initially (DAS28-CRP 3.7, DAS28-ESR 3.6) but achieved similar disease control by the 6th month (DAS28-CRP 2.7, DAS28-ESR 2.7), although higher than the first group.

Therapy discontinuation occurred in five patients due to lack of effectiveness and in two patients due to adverse events, with additional reasons including patient decision and non-medical factors. No significant adverse events of special interest were reported throughout the 12-month study period.

KOL insights

“While the data from 110 rheumatoid arthritis patients are reassuring with patients largely retaining remission, it remains unclear why patients treated with tocilizumab or sarilumab a few years would be switched to olokizumab” – Expert Opinion

Conclusion

In July 2013, UCB and R-Pharm entered into a world-wide exclusive license grant to R-Pharm to develop and commercialize olokizumab in all indications, including rheumatoid arthritis. As per the conditions of this agreement, R-Pharm will develop, register, manufacture, distribute and book sales globally. For the treatment of rheumatoid arthritis, R-Pharm has been granted market authorization for olokizumab (ARTLEGIA) in many countries (Russia, Kazakhstan, Belarus, Kyrgyzstan and Azerbaijan). 

It is worth highlighting that olokizumab is the world’s first and only registered monoclonal antibody for the treatment of rheumatoid arthritis that directly blocks the cytokine IL-6, but not its receptor.  Apart from olokizumab, there are several approved bDMARDs that target IL-6R and IL-6. Sarilumab (KEVZARA; Sanofi/Regeneron) and tocilizumab (ACTEMRA/RoACTEMRA; Roche), humanized monoclonal antibodies that target IL-6R, are the two most well-known and well-characterized. In addition, monoclonal antibodies (mAbs) that block the function of IL-6 itself include chimeric mAb siltuximab (SYLVANT; EUSA Pharma) and human mAbs satralizumab (ENSPRYNG; Roche). 

The data presented at EULAR 2024 suggests that most rheumatoid arthritis patients who transitioned from an IL-6 receptor inhibitor to olokizumab maintained remission for at least 12 months. Switching within the recommended timeframe as per guidelines helped prevent rheumatoid arthritis exacerbation and sustained remission or low disease activity for up to one year. Throughout the 12-month treatment period, no noteworthy safety concerns were observed with olokizumab.