Head-to-head trials of IL-6 inhibitors warranted in RA patients
medwireNews: Different biologic agents targeting the interleukin (IL)-6 signaling pathway may have distinct efficacy profiles in patients with rheumatoid arthritis (RA), South Korean researchers report.
Sang-Cheol Bae (Hanyang University Hospital for Rheumatic Diseases, Seoul) and Young Ho Lee (Korea University College of Medicine, Seoul) carried out an indirect comparison of regimens containing tocilizumab and sarilumab – both IL-6 receptor-targeted monoclonal antibodies – and sirukumab, a monoclonal antibody against the IL-6 cytokine, in a network meta-analysis.
The team analyzed data from 14 randomized trials involving 9753 patients with active RA and an inadequate response to methotrexate or anti-tumor necrosis factor (TNF) therapy, and used the surface under the cumulative ranking curve (SUCRA) statistical approach to convert information on the relative efficacy and safety profiles of the different IL-6 inhibitors into a ranking for each treatment.
“SUCRA simplifies the information about the effect of each treatment into a single number, which helps to guide decision-making,” say the researchers.
They found that all the IL-6-targeted agents were associated with a significantly higher probability of achieving at least a 50% improvement in ACR criteria (ACR50) compared with placebo plus methotrexate. Tocilizumab 8 mg, either in combination with methotrexate or as monotherapy, had the highest likelihood of being the best treatment regimen to achieve an ACR50 response, followed by sarilumab 200 mg alone or together with methotrexate.
In the tolerability analysis, placebo plus methotrexate had the highest probability of being the most well tolerated regimen based on treatment withdrawal due to adverse events, followed by sarilumab 150 mg plus methotrexate. Tocilizumab 8 mg monotherapy was the option associated with the lowest likelihood of being the most well tolerated treatment.
There was no significant difference in treatment withdrawals between regimens containing methotrexate plus either tocilizumab 8 mg, sirukumab 100 mg, or sarilumab 200 mg, suggesting “comparable tolerability among tocilizumab, sarilumab, and sirukumab,” write Bae and Lee.
They caution, however, that “treatment rankings derived from network meta-analyses have a substantial degree of imprecision,” meaning that “interpreting such rankings needs caution.”
And they stress that “[t]here are potential differences in serious adverse effects among biologics.”
Nevertheless, the researchers believe that their findings suggest “a difference in efficacy among anti-IL-6 biologics in patients with active RA refractory to [methotrexate] or anti-TNF therapy.”
They conclude in Clinical Rheumatology: “Long-term studies are therefore needed to determine the relative efficacy and safety of tocilizumab, sarilumab, and sirukumab in a large number of patients with active RA that inadequately responds to [methotrexate] or TNF inhibitors.”
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