Background: Psoriatic arthritis (PsA) is characterized by inflammatory arthritis, enthesitis, dactylitis, and spondylitis. Apremilast is an oral immunomodulating phosphodiesterase-4 inhibitor approved for treatment of PsA. Results from the MOSAIC study demonstrated that treatment with apremilast in patients with active PsA led to significant improvements in objective MRI indices of inflammation of the hand as assessed by the PsA MRI Score (PsAMRIS) [1] as well as significant reduction in total peripheral inflammation, including significant improvement in peripheral joint inflammation and enthesitis, as assessed by whole-body MRI (WB-MRI) [2]. Objectives: To evaluate the efficacy of apremilast on MRI endpoints, clinical outcomes, and patient reported outcomes (PROs) in patients with PsA treated with apremilast 30 mg BID in the MOSAIC study. Methods: MOSAIC (NCT03783026) was a phase 4, multicenter, single-arm, open-label study in patients with active PsA (≥3 months but ≤5 years since diagnosis, meeting CASPAR criteria) evaluating apremilast as monotherapy or in combination with stable methotrexate. Patients were treated with apremilast for 48 weeks and had contrast-enhanced MRI of the hand and WB-MRI performed at baseline, Week 24, and Week 48. All images were read and adjudicated by 2 experienced readers blinded to clinical information and acquisition time. MRI endpoints included change from baseline in the composite and total inflammation scores of hand bone marrow edema, synovitis, and tenosynovitis in fingers 2–5 as assessed by PsAMRIS at Weeks 24 and 48, as well as total peripheral inflammation index as assessed by WB-MRI. Clinical outcomes included change from baseline to Weeks 24 and 48 in swollen joint count (SJC), tender joint count (TJC), Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score, and evaluator’s global assessment of disease activity. PROs included change from baseline in Psoriatic Arthritis Impact of Disease 12 items (PsAID-12), patient assessed disease activity and pain and Health Assessment Questionnaire-Disability Index (HAQ-DI score). Results: A total of 122 patients were enrolled and received apremilast. Mean age was 47 years and 55% were women. Disease duration was limited (mean 1.9 years). At baseline, mean (SD) for MRI endpoints were composite inflammation 18.5 (17.8), total inflammation 25.8 (24.2), and peripheral inflammation 28.8 (22.5); mean (SD) SJC was 8.0 (7.2), TJC 14.6 (11.3), cDAPSA 31.9 (16.5), and evaluator’s global assessment of disease activity 5.2 (1.5); mean (SD) PsAID-12 4.75 (1.87), patient’s global assessment of disease activity 5.6 (1.8), patient’s assessment of pain 5.6 (1.8), and HAQ-DI 1.01 (0.57). Apremilast treatment resulted in significant changes from baseline to Weeks 24 and 48 in the composite inflammation score and total inflammation score by PsAMRIS, and peripheral inflammation index by WB-MRI (Figure 1). Significant reductions were observed with clinical outcomes and PROs at weeks 24 and 48, including SJC, TJC, cDAPSA, evaluator’s global assessment of disease activity, PsAID-12, patient’s global assessment of disease activity, patient’s assessment of pain, and HAQ-DI (Figure 2). Conclusion: Patients with PsA treated with apremilast had significant improvements in MRI endpoints, clinical outcomes, and PROs at Weeks 24 and 48, confirming the effect of apremilast on clinical and inflammatory manifestations of PsA. These results offer important insights on the effect of apremilast in PsA and highlight the value of using MRI of the hand and whole body as measures of inflammatory disease activity and change following treatment. REFERENCES: [1] Østergaard M, et al. Ann Rheum Dis. 2023;82:341-42.[2] Østergaard M, et al. Ann Rheum Dis. 2023;82:2000-01. Acknowledgements: This clinical trial was sponsored by Amgen Inc. Medical writing support was funded by Amgen Inc. and provided by Martha Mutomba (on behalf of Amgen Inc) and Jessica Ma, employee of and stockholder in Amgen Inc. Disclosure of Interests: Philip J. Mease AbbVie, Amgen Inc., Eli Lilly, Janssen, Novartis, Pfizer, and UCB, AbbVie, Acelvrin, Amgen Inc., Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun, UCB, Aclaris, Boehringer Ingelheim, GlaxoSmithKline, Moonlake Pharma, Takeda, and Ventyx, AbbVie, Acelvrin, Amgen Inc., Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun, and UCB, Walter P Maksymowych AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, AbbVie, Novartis, Pfizer, and UCB, Mikael Boesen AbbVie, Celgene, Eli Lilly, Image Analysis Group, Novartis, Pfizer, and UCB, AbbVie, Celgene, Eli Lilly, Image Analysis Group, Novartis, Pfizer, and UCB, AbbVie, Celgene, and Novartis, Robert G Lambert Calyx, CARE Arthritis Limited, and Image Analysis Group, Guillermo Valenzuela AbbVie, Amgen Inc., AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Genentech, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Pharmacia, Radius, Regeneron, Sanofi, Takeda, and UCB, 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, Mallinckrodt and Novartis, Michael Bubb Amgen Inc., BMS, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, and UCB, Olga Kubassova: None declared, Frank Behrens Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Amgen, Celgene, MSD, Novartis, Janssen, Lilly, Sanofi, Biogen, Sandoz, GSK, Abbvie, Pfizer, UCB, BMS, Celgene, Amgen, Novartis, Janssen, Lilly, MSD, Sanofi, GSK, Abbvie, Pfizer, Roche, Chugai, Prophylix, Rallybio, BMS, Novartis, Amgen, Janssen, Jyotsna Reddy Amgen Inc, Amgen Inc, Stephen Colgan Amgen Inc, Amgen Inc, Yuri Klyachkin Amgen Inc, Amgen Inc, Cynthia Deignan Amgen Inc, Amgen Inc, Zhenwei Zhou Amgen Inc, Amgen Inc, Mikkel Østergaard Amgen Inc, Amgen IncFigure 1Improvements in MRI scores of inflammation during apremilast therapy. Figure 2Improvements in clinical disease activity scores and patient-reported outcomes during apremilast therapy.

Background: Apremilast is an oral phosphodiesterase 4 inhibitor with a unique immunomodulatory mechanism of action and is approved for the treatment of psoriatic arthritis (PsA). Although peripheral arthritis is the most frequent clinical feature in patients with PsA, axial involvement may occur in up to 50% of patients with PsA, causing inflammatory back pain, stiffness, and changes on imaging. Here, we used whole-body magnetic resonance imaging (WB-MRI) to evaluate the efficacy of apremilast 30 mg twice daily on axial inflammation in patients with PsA. Objectives: To evaluate the efficacy of apremilast on axial inflammation in PsA. Methods: The MOSAIC study was a phase 4, single-arm, open-label trial that evaluated up to 48 weeks of apremilast treatment (with or without stable methotrexate) in patients with active PsA (per Classification Criteria for Psoriatic Arthritis [CASPAR]). Contrast-enhanced WB-MRI was performed at baseline, week 24, and week 48, and images were evaluated and adjudicated by two experienced readers who were blinded to time point and response to apremilast. In patients deemed to have PsA spondylitis by the investigator and a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Item 2 (back pain) ≥4, MRI axial inflammation was assessed by calculating the least squares mean changes from baseline to week 24 and week 48 in the Canada-Denmark (CANDEN) total spine inflammation score and subscores (assessing individual anatomical locations including posterolateral elements), the Spondyloarthritis Research Consortium of Canada (SPARCC) spine score, and the SPARCC sacroiliac joint (SIJ) inflammation score. Results: Overall, 122 patients were treated with apremilast. At baseline, the mean age was 47 years, 55% were women, mean PsA duration was 1.9 years, mean CANDEN spine score was 5.8, mean SPARCC spine score was 5.4, and mean SPARCC SIJ inflammation score was 2.7. Of the 40 patients deemed to have PsA spondylitis by the investigator and a BASDAI Item 2 ≥4, 39 patients were analyzed for axial inflammation. At weeks 24 and 48, CANDEN total spine inflammation score, vertebral body, posterior elements, corner, non-corner, and posterolateral elements inflammation subscores were significantly reduced with apremilast relative to baseline. No significant change in facet joint inflammation subscore, SPARCC spine, or SPARCC SIJ scores were observed (Figure 1). Conclusion: In patients with early PsA, apremilast reduced axial inflammation as assessed by the CANDEN MRI scoring system which provided a comprehensive and detailed anatomy-based quantification of inflammatory changes in the spine. Apremilast significantly reduced inflammation both in vertebral bodies and in posterolateral elements of the spine after 24 and 48 weeks of treatment. REFERENCES: NIL. Acknowledgements: This study was funded by Amgen Inc. Writing support was funded by Amgen Inc. and provided by Shannon Rao, PhD, employee of and stockholder in Amgen Inc. Disclosure of Interests: Mikkel Østergaard AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, AbbVie, Amgen Inc., BMS, Merck, Celgene, and Novartis, Walter P Maksymowych CARE Arthritis Limited, AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, AbbVie, Novartis, Pfizer, and UCB, Robert G Lambert Calyx, CARE Arthritis Limited, and Image Analysis Group, Mikael Boesen AbbVie, Celgene, Eli Lilly, Image Analysis Group, Novartis, Pfizer, and UCB, Image Analysis Group, AbbVie, Celgene, Eli Lilly, Image Analysis Group, Novartis, Pfizer, and UCB, AbbVie, Celgene, and Novartis, Guillermo Valenzuela AbbVie, Amgen Inc., AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Genentech, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Pharmacia, Radius, Regeneron, Sanofi, Takeda, and UCB, 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, Mallinckrodt and Novartis, Michael Bubb AbbVie, Celgene, Eli Lilly, Image Analysis Group, Novartis, Pfizer, and UCB, Image Analysis Group, AbbVie, Celgene, Eli Lilly, Image Analysis Group, Novartis, Pfizer, and UCB, AbbVie, Celgene, and Novartis, Olga Kubassova Image Analysis Group, Image Analysis Group, Xenofon Baraliakos Abbvie, Amgen, BMS, Chugai, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB, Novartis and Abbvie, Carlo Selmi AbbVie, Amgen, Alfa-Sigma, Biogen, Eli-Lilly, EUSA Pharma - Recordati, Galapagos, Janssen, Novartis, Octapharma, Pfizer, Recordati Rare Disease, and SOBI, AbbVie, Amgen, Alfa-Sigma, Biogen, Eli-Lilly, EUSA Pharma - Recordati, Galapagos, Janssen, Novartis, Octapharma, Pfizer, Recordati Rare Disease, and SOBI, AbbVie, Amgen, Janssen, Novartis, and Pfizer, Stephen Colgan Amgen Inc, Amgen Inc, Yuri Klyachkin Amgen Inc., Amgen Inc., Cynthia Deignan Amgen Inc., Amgen Inc., Zhenwei Zhou Amgen Inc., Amgen Inc., Philip J. Mease AbbVie, Amgen Inc., Eli Lilly, Janssen, Novartis, Pfizer, and UCB, AbbVie, Amgen Inc., Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun, UCB, Boehringer Ingelheim and GlaxoSmithKline, AbbVie, Amgen Inc., Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun, and UCB,Figure 1LS mean changes from baseline to weeks 24 and 48 in CANDEN spine total score and component subscores, SPARCC spine score, and SPARCC SIJ score.

Background Psoriatic arthritis (PsA) is characterized by various patterns of inflammatory arthritis, enthesitis, dactylitis, and spondylitis. Apremilast is an oral immunomodulating phosphodiesterase-4 inhibitor that is indicated for treatment of PsA. Whole-body magnetic resonance imaging (WB-MRI) allows assessment of joints and entheses of the entire body in one examination when using the Outcome Measures in Rheumatology Clinical Trial (OMERACT) MRI whole-body scoring system for inflammation in peripheral joints and entheses (MRI-WIPE), which has not previously been applied in a clinical trial. Here we evaluate the efficacy of apremilast 30 mg BID (APR) on peripheral inflammation indices as measured by WB-MRI. Objectives To evaluate how APR affects inflammation in peripheral joints and entheses of patients with PsA as assessed by WB-MRI. Methods The phase 4 MOSAIC study was a multicenter, single-arm, open-label study evaluating APR (either as monotherapy or in combination with stable methotrexate) in patients with active PsA (diagnosis ≥3 months but ≤5 years, meeting the CASPAR criteria for PsA) for treatment up to 48 weeks. WB-MRI was performed at baseline, Week 24, and Week 48. Images were read and adjudicated by 2 experienced readers who were blinded to time of acquisition and clinical information. From WB-MRI, changes in the total peripheral inflammation index (83 joints and 33 entheses) were calculated using the OMERACT MRI-WIPE scoring system, as were changes in separate enthesitis and joint inflammation WB-MRI indices (WIPE-enthesitis and WIPE-joint inflammation). Changes in the heel enthesitis inflammation index (HEMRIS), the hip joint inflammation MRI index (HIMRISS), and the knee joint inflammation MRI index (KIMRISS) were explored. Results Overall, 122 patients were enrolled and treated with APR; 55% were women, mean age was 47 years, and patients had a mean duration of PsA of 1.9 years. The least squares mean (95% CI) change from baseline in total WIPE score based on total peripheral inflammation index (including both joint and enthesitis inflammation) as assessed by WB-MRI was -3.49 (-5.46, -1.52) at Week 24 and -4.06 (-6.39, -1.72) at Week 48, indicating significant improvement in peripheral inflammation (Figure 1). Significant improvements were also observed in the WIPE-joint inflammation scores at both Week 24 and 48, and in the WIPE-enthesitis scores at Week 48 (Figure 1). Both the heel enthesitis inflammation index (HEMRIS) and the hip joint inflammation MRI index (HIMRISS) showed little change, while the knee joint inflammation MRI index (KIMRISS) showed numerical, but not significant, improvement (Figure 1). No new safety signals were identified. Conclusion Patients with PsA treated with APR experienced a significant reduction in total peripheral inflammation, including significant improvement in peripheral joint inflammation and enthesitis, as assessed by WB-MRI. Results highlight the efficacy of APR on inflammatory manifestations of PsA as well as the benefit of using WB-MRI as a measure of inflammatory disease activity. Acknowledgements This 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 Interests Mikkel 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 Shareholder of: Employment by and stock ownership in Image Analysis Group, 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: Grant/research support and consultant for AbbVie, Amgen Inc., Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun, and UCB; 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.

Le rhumatisme psoriasique (RPso) oligoarticulaire peut avoir un impact significatif sur la qualité de vie, et ce, malgré un nombre limité d’articulations touchées. L’étude FOREMOST vise à évaluer l’efficacité de l’aprémilast (APR) chez des patients avec une atteinte articulaire limitée (définie par 2–8 articulations actives), en termes d’activité de maladie, en appliquant un score d’activité minimale de la maladie modifié (MDA-Artic). FOREMOST (NCT03747939) est une étude randomisée, en double aveugle, contrôlée vs placebo (PBO) de phase IV, multicentrique. Les patients éligibles avaient un diagnostic récent de RPso (≤ 5 ans) avec une atteinte articulaire limitée (nombre d’articulations gonflées [NAG] > 1 à ≤ 4 et douloureuses [NAD] > 1 à ≤ 4 sur 66–68 articulations évaluées). Les articulations actives à l’inclusion étaient désignées comme « sentinelles ». La randomisation s’est faite selon un rapport de 2:1 entre APR ou PBO durant 24 semaines, avec un échappement précoce à la semaine 16 (S16). Le critère d’évaluation principal était la proportion de patients obtenant un MDA-Artic (NAG ≤ 1, NAD ≤ 1 et 3/5 autres des critères suivants : surface cutanée atteinte (SCA) ≤ 3 %, évaluation de la douleur par échelle visuelle analogique [EVA] ≤ 15/100, évaluation globale patient (EGP) ≤ 20, Health Assessment Questionnaire Disability Index [HAQ-DI] ≤ 0,5, score d’enthèses de Leeds [LEI] ≤ 1). Les critères secondaires à S16 incluaient la proportion de patients obtenant : un Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) de rémission (REM, ≤ 4) ou de faible activité (LDA, > 4 à ≤ 13), un EGP ≤ 20, une douleur EVA ≤ 15, un PsA Disease Activity Score (PASDAS) de réponse bonne ou modérée, ainsi que la variation du PsA Impact of Disease 12 (PsAID-12) par rapport à l’inclusion. Des analyses exploratoires ont été effectuées pour toutes les articulations, ainsi que des analyses post hoc chez les patients présentant 2–4 articulations actives. Parmi les 308 patients randomisés (APR : n = 203 ; PBO : n = 105), la durée moyenne du RPso était de 9,9 (ET 10,2) mois, l’âge moyen de 50,9 (ET 12,5) ans. 39,9 % des patients recevaient un csDMARD en combothérapie. Dans l’ensemble de la population de l’étude, la réponse MDA-Artic (critère principal évalué en fonction des articulations sentinelles) a été obtenue significativement chez plus de patients sous APR (33,9 %) vs PBO (16,0 %) à S16 (p = 0,0008). Les caractéristiques cliniques étaient similaires entre les groupes de patients présentant une atteinte de ≤ 4 et > 4 articulations à l’inclusion. Au total, 268 (87 %) patients présentaient ≤ 4 articulations actives à l’inclusion. Une analyse post hoc a montré des taux de réponse MDA-Artic similaires chez les patients avec une atteinte de 2–4 articulations (APR : 34,4 %, PBO : 17,2 %) par rapport à l’ensemble de la population de l’étude à S16. FOREMOST est la 1re étude internationale randomisée, contrôlée évaluant les RPso oligoarticulaires récents. Cette étude démontre l’efficacité de l’APR chez ces patients, avec l’obtention d’une réponse MDA-Artic deux fois plus fréquente dans le bras APR que PBO à S16.

Background It has been suggested that greater skin involvement in patients with psoriatic arthritis (PsA) may be associated with greater joint disease activity. Objectives To assess the impact of APR on PsA disease domains in patients with BSA <3% vs BSA ≥3% at 52 weeks using pooled data from 2 phase 3 trials. Methods PALACE 1 & 2 were randomized, placebo (PBO)-controlled, phase 3 studies in patients with active PsA. Eligible patients had ≥3 swollen and ≥3 tender joints despite prior treatment with a conventional systemic Disease Modifying Antirheumatic Drug (csDMARD) and/or biologic DMARD (bDMARD) or concurrent treatment with csDMARD. Patients were randomized to receive APR or PBO for up to 24 weeks, after which all patients received APR until Week 52. This ad-hoc analysis includes pooled data from patients randomized to APR 30 mg BID at Week 0 in these studies. Assessments included change from baseline at Week 52 in Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), swollen joint count (SJC), tender joint count (TJC), patient assessment of pain visual analog scale (VAS), and Patient Global Assessment of Disease Activity (PtGA) VAS stratified by baseline psoriasis body surface area (BSA) involvement (<3% vs ≥3%). Results Of 330 patients randomized to APR 30 mg BID at Week 0, 171 had BSA <3% and 159 had BSA ≥3%. Of those with available data, 98.2% of patients with BSA <3% and 100% of patients with BSA ≥3% had a history of psoriasis; mean BSA at baseline was 1.2 in the <3% group and 14.3 in the ≥3% group. More patients with BSA ≥3% at baseline were men with higher rates of nail and SJC involvement, and slightly higher rates of oligoarthritis and TJC (Table 1). At Week 52, both subgroups showed mean decreases (improvement) from baseline in clinical parameters with APR treatment, including cDAPSA (BSA <3%: -18.0, BSA ≥3%: -23.3), SJC (BSA <3%: -6.1, BSA ≥3%: -8.7), TJC (BSA <3%: -10.1, BSA ≥3%: -13.0), Patient Assessment of Pain (BSA <3%: -15.5, BSA ≥3%: -18.0), and PtGA (BSA <3%: -11.8, BSA ≥3%: -16.8) (Table 1). There were numerically greater decreases in these parameters among patients with baseline BSA ≥3% than those with BSA <3%. Improvements in enthesitis and dactylitis were also observed in both subgroups. Conclusion Patients with PsA in PALACE 1 & 2 with higher BSA had higher disease activity in some disease domains at baseline. Both BSA subgroups showed improvement with APR at Week 52 regardless of disease severity, although numerically greater improvements were seen in patients with BSA ≥3%. To our knowledge, this is a novel analysis assessing treatment efficacy in patients with PsA by level of skin involvement. Acknowledgements This study was sponsored by Amgen Inc. Writing support was funded by Amgen Inc. and provided by Rebecca Lane, PhD of Peloton Advantage, LLC, an OPEN Health company, and Dawn Nicewarner, PhD, employee of and stockholder in Amgen Inc. Disclosure of Interests Alvin F. Wells Speakers bureau: AbbVie, Alexion, Amgen Inc., BMS, Celgene, Horizon, Lilly, Novartis, and UCB – consultant and speakers bureau, Consultant of: AbbVie, Alexion, Amgen Inc., BMS, Celgene, Horizon, Lilly, Novartis, and UCB – consultant and speakers bureau, Grant/research support from: AbbVie, Celgene, and Lilly – grant/research support, Lichen Teng Shareholder of: Amgen Inc. – employees and stockholders, Employee of: Amgen Inc. – employees and stockholders, Stephen Colgan Shareholder of: Amgen Inc. – employees and stockholders, Employee of: Amgen Inc. – employees and stockholders, Cynthia Deignan Shareholder of: Amgen Inc. – employees and stockholders, Employee of: Amgen Inc. – employees and stockholders, Shauna Jardon Shareholder of: Amgen Inc. – employees and stockholders, Employee of: Amgen Inc. – employees and stockholders, Yuri Klyachkin Shareholder of: Amgen Inc. – employees and stockholders, Employee of: Amgen Inc. – employees and stockholders, Amar Majjhoo Speakers bureau: AbbVie, Amgen Inc., Eli Lilly, and Jansen – consultant, speaker, Consultant of: AbbVie, Amgen Inc., Eli Lilly, and Jansen – consultant, speaker, Arthur Kavanaugh Consultant of: AbbVie, Amgen Inc., BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB – consultant.

Background Psoriatic 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. Objectives To evaluate the efficacy of APR on inflammation and imaging outcomes and the safety profile of APR in this setting. Methods MOSAIC (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. Results A 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. Conclusion Pts 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. Acknowledgements This 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 Interests Mikkel 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.