Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial
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  • Published on:
    Reply to Dr Kunal Chandwar, Senior Resident, Department of Clinical Immunology and Rheumatology King George’s Medical University
    • Bernard Combe, Professor of Rheumatology, Head of the department of Rheumatology University of Montpellier and CHU Montpellier, France

    We sincerely thank Dr Chandwar for his interest in our report of this pivotal trial of filgotinib vs placebo or adalimumab in patients with rheumatoid arthritis (RA) and inadequate response to methotrexate.
    The primary objective of the trial was to evaluate the effects of filgotinib vs placebo as measured by the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12.[1] We agree that the study of RA would benefit from new and better indicators of disease activity, particularly when evaluating treatment modalities with direct effects on individual response components. However, until we have such instruments, we are bound to use those that are available, validated, and recognized by regulatory authorities.
    Filgotinib 200 mg demonstrated noninferiority to adalimumab based on Disease Activity Scale in 28 joints with C-reactive protein (CRP) and Clinical Disease Activity Index (CDAI) low disease activity (LDA) and remission; analyses with filgotinib 100 mg were not alpha protected, hence noninferiority could not be claimed. [1]
    As we noted in the paper, efficacy shown by CDAI suggests the effects of Janus kinase (JAK) inhibition on CRP were not solely responsible for the treatment effect of filgotinib 200 mg.[1] It is possible that treatment differences between filgotinib 200 mg and adalimumab for CDAI LDA/remission may be, at least in part, a product of a greater effect of filgotinib on pain via JAK...

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    Conflict of Interest:
    Honoraria from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Lilly, Merck, Novartis, Pfizer, Roche-Chugai, Sanofi and
    UCB; research grants from Novartis, Pfizer, and Roche.
  • Published on:
    Correspondence on “Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial” by “Combe et al.”‘.
    • Kunal Chandwar, Senior Resident, Department of Clinical Immunology and Rheumatology King George's Medical University

    We read with great interest the article by Combe et at.(1) Regarding Filgotinib in Rheumatoid arthritis. We have a few points to raise. Filgotinib is a JAK inhibitor and affects the IL-6 pathway hence when taking a primary endpoint (ACR20) that is dependent on ESR/CRP with a drugs that acts on the IL-6 axis and reduces acute phase reactants more efficiently than Adalimumab, claiming superiority can be flawed. The same holds true for comparing Adalimumab and Filgotinib with respect to DAS28-CRP and trying to prove superiority or non-inferiority. We need better disease activity indicators when comparing drugs that inhibit the IL-6 pathway and hence reduce ESR/CRP more effectively than those who don’t.
    Though the authors do point out that CDAI responses were similar – that could also be due to better pain control with JAK inhibitors due to their effect on pain pathway.
    At the same time it needs to be pointed out that though both Baricitinib and Upadacitinib did prove superiority to Adalimumab at week 12 with respect to ACR20 responses in the RA-BEAM(3) (69.6 with Baricitinib vs 61.2 with Adalimumab) and SELECT-COMPARE(4) (70.5% with Upadacitinib 15mg vs 63% with Adalimumab) but similar finidng were not observed with Filgotinib 100mg. The other interesting finding was that of higher response rates compared to ORAL standard(2), RA-BEAM(3) and SELECT-COMPARE(4) trials with other JAK inhibitors in terms of ACR20 responders for Adalimumab (58-63% vs 70%) and Placebo...

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    Conflict of Interest:
    None declared.