Pos0226 apremilast Reduces Inflammation as Measured by Mri of the Hand in Patients With Psoriatic Arthritis: Primary Results From the Phase 4 Mosaic Study

Abstract

BackgroundPsoriatic arthritis (PsA) is characterized by inflammatory arthritis, enthesitis, dactylitis, and spondylitis. Apremilast is an oral immunomodulating phosphodiesterase-4 inhibitor approved for the treatment of PsA. The impact of apremilast on objective measures of inflammation and structural progression of PsA has not yet been characterized. Here, we evaluate the efficacy of apremilast 30 mg BID (APR) on inflammation measured by dedicated MRI of the hand.ObjectivesTo evaluate the efficacy of APR on inflammation and imaging outcomes and the safety profile of APR in this setting.MethodsMOSAIC (NCT03783026) was a phase 4, multicenter, single-arm, open-label study in patients (pts) with active PsA (≥3 months but ≤5 years since diagnosis, meeting CASPAR criteria for PsA) evaluating APR as monotherapy or in combination with stable methotrexate. Pts were treated with APR for 48 weeks and had MRI of the hand (contrast-enhanced) performed at baseline (BL), Week 24, and Week 48. All images were read and adjudicated by 2 experienced readers blinded to clinical information and time of acquisition. The primary endpoint was change from BL in the composite score of hand bone marrow edema (BME), synovitis, and tenosynovitis in fingers 2–5, as assessed by the PsA MRI Score (PsAMRIS) at Week 24. Total inflammation score, comprised of BME, synovitis, tenosynovitis, and periarticular inflammation in fingers, was also assessed. Structural progression was assessed by the total hand damage score (determined by bone erosion and bone proliferation in fingers 2–5). Subgroup analyses based on BL disease activity as measured by Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) were performed for key endpoints.ResultsA total of 122 pts enrolled and received APR. Mean age was 47 years, 55% were women, and mean duration of PsA was 1.9 years. The Full Analysis Set (FAS) included 98 pts evaluable for the primary endpoint (having BL and Week 24 data); 4 had major protocol deviations and 94 were evaluable as part of the per protocol (PP) population. The least-squares (LS) mean (95% CI) change from BL in the composite inflammation score of BME, synovitis, and tenosynovitis as assessed by PsAMRIS (FAS) was -2.32 (-4.73, 0.09) at Week 24 and -2.91 (-5.45, -0.37) at Week 48 (Figure 1). In the PP population, the LS mean (95% CI) change from BL in the composite score at Weeks 24 and 48 indicated a significant reduction of disease activity (Figure 1). Significant improvements from BL were seen in total inflammation scores (BME + synovitis + tenosynovitis + periarticular inflammation) in the FAS (Figure 1). The structural outcome indicated by the total hand damage score, including bone erosion, showed no significant change from BL to Week 48 (Figure 1). Pts also experienced significant improvements from BL in cDAPSA at Weeks 24 and 48 (Figure 1). Subgroup analyses based on disease activity at BL showed significant improvements from BL in inflammation in pts with moderate disease activity (ModDA; cDAPSA score >13 to ≤27) and no significant change from BL in total damage (Figure 1). Though it was insignificant, pts with high disease activity (HDA; cDAPSA score >27) did have improvement from BL in inflammation indices (Figure 1). Common treatment-emergent adverse events were diarrhea (33.6%), nausea (12.3%), headache (10.7%), nasopharyngitis (7.4%), and dyspepsia (6.6%). No new safety signals were identified.ConclusionPts with PsA treated with APR had improvements in both clinical indices and objective MRI indices of inflammation assessed by PsAMRIS in the target hand at Week 24 and Week 48, confirming an effect of APR on clinical and inflammatory manifestations of PsA. Pts with ModDA seemed to have greater improvement from BL in MRI inflammation scores than pts with HDA. No significant structural progression was observed. These results offer important insights on the effect of apremilast in PsA and highlight the value of using MRI and PsAMRIS as measures of inflammatory disease activity and change following treatment.Figure 1.AcknowledgementsThis study was funded by Amgen Inc. Writing support was funded by Amgen Inc. and provided by Christina Mulvihill, PharmD, of Peloton Advantage, LLC, an OPEN Health company, and Scott Houck, PhD, employee of and stockholder in Amgen Inc.Disclosure of InterestsMikkel Østergaard Speakers bureau: speaker and/or consultancy fees from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Consultant of: speaker and/or consultancy fees from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Grant/research support from: Received research grants from AbbVie, Amgen Inc., BMS, Merck, Celgene, and Novartis, Walter P Maksymowych Consultant of: Received consulting fees from AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: grant/research support from AbbVie, Novartis, Pfizer, and UCB, Employee of: chief medical officer of CARE Arthritis Limited, Mikael Boesen Shareholder of: reports stock ownership in Image Analysis Group, Speakers bureau: speaker and/or consultancy fees from AbbVie, Celgene, Eli Lilly, Image Analysis Group, Novartis, Pfizer, and UCB, Consultant of: speaker and/or consultancy fees from AbbVie, Celgene, Eli Lilly, Image Analysis Group, Novartis, Pfizer, and UCB, Grant/research support from: Received grants from AbbVie, Celgene, and Novartis, Robert G Lambert Consultant of: Received consulting fees from Calyx, CARE Arthritis Limited, and Image Analysis Group, Guillermo Valenzuela Speakers bureau: speakers bureau for AbbVie, Amgen Inc., AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Genentech, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Pharmacia, Radius, Regeneron, Sanofi, Takeda, and UCB, Consultant of: consultant for AbbVie, Alexion, Amgen Inc., Boehringer Ingelheim, Celgene, Eli Lilly, Esaote, Exagen, Genentech, Gilead, Global Health Living, Horizon, Image Analysis Group, Janssen, Merck, Novartis, Pfizer, Regeneron, Sandoz, Sanofi, and UCB, Grant/research support from: Received grant/research support from Mallinckrodt and Novartis, Michael Bubb Grant/research support from: Research grants from Amgen Inc., BMS, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, and UCB., Olga Kubassova Employee of: Employment by and stock ownership in Image Analysis Group, Jyotsna Reddy Shareholder of: Employment by and stock ownership in Amgen Inc., Employee of: Employment by and stock ownership in Amgen Inc., Stephen Colgan Shareholder of: Employment by and stock ownership in Amgen Inc., Employee of: Employment by and stock ownership in Amgen Inc., Yuri Klyachkin Shareholder of: Employment by and stock ownership in Amgen Inc., Employee of: Employment by and stock ownership in Amgen Inc., Cynthia Deignan Shareholder of: Employment by and stock ownership in Amgen Inc., Employee of: Employment by and stock ownership in Amgen Inc., Lihua Tang Shareholder of: Employment by and stock ownership in Amgen Inc., Employee of: Employment by and stock ownership in Amgen Inc., Maria Paris Shareholder of: Employment by and stock ownership in Amgen Inc., Employee of: Employment by and stock ownership in Amgen Inc., Philip J Mease Speakers bureau: speakers bureau for AbbVie, Amgen Inc., Eli Lilly, Janssen, Novartis, Pfizer, and UCB., Consultant of: consultant for Boehringer Ingelheim and GlaxoSmithKline, Grant/research support from: Grant/research support and consultant for AbbVie, Amgen Inc., Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun, and UCB.

Advances in Imaging for Clinical Trials in Rheumatic Diseases

“…A total of 83 joints are scored separately for synovitis and osteitis, and 33 entheses are scored separately for soft tissue inflammation and osteitis [49,50]. The first data using this method in an open label trial of apremilast was recently presented [51]. Significant amelioration of peripheral and entheseal inflammation was demonstrable after 24 weeks of treatment.…”