{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:07:27Z","timestamp":1779379647675,"version":"3.53.1"},"reference-count":38,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"unspecified","delay-in-days":50,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001009","name":"Bristol Myers Squibb Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2026,4,19]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background\/Purpose<\/jats:title>\n                    <jats:p>CC-99677 (BMS-986371) is a novel, small-molecule covalent inhibitor of mitogen-activated protein kinase-activated protein kinase 2 (MK2). We aimed to evaluate the dose-dependent efficacy and safety of CC-99677 compared with placebo in subjects with ankylosing spondylitis (AS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a phase II, multicentre, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of CC-99677 in subjects with AS. Subjects were randomised 1:1:1 to once-daily CC-99677 150 mg, CC-99677 60 mg or placebo. Main inclusion criteria were fulfilment of the modified New York criteria for AS, active symptoms (Bath Ankylosing Spondylitis Disease Activity Index \u22654\u2009and total back pain \u22654) despite \u22652 non-steroidal anti-inflammatory drugs and na\u00efve to biologic disease-modifying anti-inflammatory drugs. The primary end point was Assessment of SpondyloArthritis international Society 20% improvement criteria (ASAS20) response at 12 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>147 subjects were enrolled and 123 (83.7%) subjects completed treatment in the double-blind, placebo-controlled period. The main reason for discontinuation was study termination based on futility at interim analysis. Baseline characteristics were typical of an AS trial population. Treatment with CC-99677 was generally well-tolerated. ASAS20 and ASAS40 at week 12 were 51.2% and 25.6% in the CC-99677 60 mg group, 56.1% and 34.1% in the 150 mg group and 48.8% and 22.0% in the placebo group. No significant treatment group differences were noted for secondary end points. There were trends in active treatment groups for improvement in MRI spine and sacroiliac joint inflammation scores but minimal inhibition of pro-inflammatory cytokines in serum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Inhibition of MK2 by CC-99677 was insufficient to lead to significant clinical benefits in AS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04947579\">NCT04947579<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  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