medwireNews: Sarilumab shows greater efficacy relative to adalimumab or methotrexate monotherapy among rheumatoid arthritis (RA) patients with high baseline interleukin-6 (IL-6) levels than it does among those with low or medium levels, study findings indicate.
The post-hoc analysis of data from the phase 3 MONARCH and MOBILTY trials also found that high baseline IL-6 was associated with significantly more joint damage at baseline and over time than low IL-6.
Anita Boyapati (Regeneron Pharmaceuticals, Inc, Tarrytown, New York, USA) and co-investigators therefore believe that “serum IL-6 could be a useful marker to guide treatment choices for patients with RA, if validated prospectively in an independent clinical study.”
In MONARCH, patients with moderate-to-severe RA who had an inadequate response or intolerance to methotrexate were randomly assigned to receive sarilumab 200 mg (n=184) or adalimumab 40 mg (n=185) every 2 weeks for 24 weeks.
The primary analysis found that the efficacy of sarilumab was significantly greater than that of adalimumab in the overall intention-to treat population.
In the current analysis, there was a significant interaction between outcome and baseline IL-6, such that individuals in the highest tertile of baseline IL‐6 (n=100; median 64.7 pg/mL) had a greater magnitude of response with sarilumab versus adalimumab across several clinical parameters than individuals in the lowest IL‐6 tertile (n=100; median 2.4 pg/mL).
For example, individuals with high IL-6 were a significant 10.5 times more likely to achieve an ACR70 response at week 24 with sarilumab than with adalimumab.
And the odds ratios for achieving DAS28-ESR remission (<2.6 points), DAS-CRP remission (<2.6 points), and an HAQ-DI improvement of at least 0.22 points among the people with high IL-6 were a significant 33.9, 18.4, and 5.0, respectively, with sarilumab versus adalimumab.
By contrast, there was no difference between the two treatments in any of these outcomes for patients with low or medium IL-6 levels.
In MOBILTY, study participants were randomly assigned to receive sarilumab 150 mg (n=400), 200 mg (n=399), or placebo (n=398) every 2 weeks, each in combination with weekly methotrexate for 52 weeks.
In this case, the researchers found that patients with high IL‐6 were more likely to experience joint progression at 52 weeks than those with low or medium IL-6 levels, irrespective of treatment assignment, but treatment with sarilumab 200 mg substantially slowed this progression relative to placebo.
Indeed, the mean change in mTSS at week 52 was 0.77 among the individuals with high IL-6 who received sarilumab 200 mg and 4.67 among those who received placebo. For those with low IL-6 levels the corresponding values were 0.11 and 1.51.
Similar to the findings of the MONARCH study, the MOBILITY data also showed that individuals receiving sarilumab plus methotrexate were more likely to achieve a clinical response based on multiple endpoints than those receiving placebo plus methotrexate.
Writing in Arthritis & Rheumatolgoy, Boyapati and co-authors conclude: “IL‐6 may be a prognostic marker of disease progression and severity, and patients with high IL‐6 may be likely to benefit from sarilumab compared with adalimumab or methotrexate.”
However, they note that as a post-hoc analysis, the data “must be interpreted with caution; neither trial was designed to prospectively evaluate the predictive value of IL-6 as a biomarker in RA.”
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