Adalimumab–methotrexate combination merits further investigation in axSpA
medwireNews: The addition of methotrexate to adalimumab may reduce immunogenicity and improve pharmacokinetics of the tumor necrosis factor (TNF) inhibitor in patients with axial spondyloarthritis (axSpA), suggest results from the CoMARIS trial.
The phase 4 study included 107 patients with axSpA and no prior adalimumab exposure who were randomly assigned to receive subcutaneous adalimumab 40 mg every other week, either with or without subcutaneous methotrexate 10 mg/week commencing 2 weeks before the initiation of adalimumab.
As reported in RMD Open, the proportion of patients positive for anti-drug antibodies (>12 AU/mL) after 26 weeks of treatment – the primary trial outcome – was significantly lower in the group given adalimumab plus methotrexate compared with the adalimumab monotherapy arm, at 25.0% versus 47.3%.
Moreover, linear mixed-effect models demonstrated that the median serum adalimumab concentration was significantly higher among patients taking both therapies versus adalimumab alone at weeks 4, 8, 12, and 26. At all timepoints, the median adalimumab concentration was highest among patients negative for anti-drug antibodies, followed by those with low (13–100 AU/mL) antibody levels, and lowest among those with high (>100 AU/mL) levels.
These findings are important because “immunogenicity to monoclonal antibodies [such as adalimumab] is an unwanted outcome responsible for loss of response and treatment discontinuation,” say the CoMARIS (Combination of Methotrexate and Adalimumab on Reduction of Immunisation in Ankylosing Spondylitis) investigators.
However, they note that because some patients given the combination therapy were positive for anti-drug antibodies at week 26, despite “good adherence” to methotrexate, “the proposed scheme could not completely abrogate the immunogenicity of adalimumab in all [methotrexate]-treated patients.”
There was also no significant difference in treatment efficacy in the two groups; the median ASDAS at week 26 was 1.6 points and was similar in both arms, and a comparable proportion of participants given the combination versus adalimumab alone were classified as ASDAS responders (54 vs 62%).
Denis Mulleman (University of Tours, France) and fellow researchers also conducted a retrospective analysis to investigate factors associated with adalimumab maintenance among 104 CoMARIS participants after a median 210 weeks of follow-up. Patients remained on adalimumab for a median of 88 weeks, and continuation of methotrexate beyond week 26 was significantly associated with long-term adalimumab maintenance on multivariate analysis.
Therefore, the “prolonged co-treatment of [methotrexate] with adalimumab may […] improve the therapeutic maintenance of adalimumab,” say the investigators.
And they conclude: “The quantification of the effect of [methotrexate] on clinical outcomes such as ASDAS should be assessed further than 26 weeks in future studies.”
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