Background The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE. Methods MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have least three swollen and three tender joints with hand involvement and at least one active enthesitis site according the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with ClinicalTrials.gov (NCT03783026). Findings Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Ofthese 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was -232 (95% CI -473 to 009). (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment- emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment- emergent adverse events were considered to be related to apremilast. Interpretation Apremilast improved inflammation in joints and entheses on assessment of MRI measures in the hand and the whole body. Our findings encourage the use of MRI, including whole-body MRI, as an objective outcome measure in trials in patients with psoriatic arthritis.

OBJECTIVES:To assess the efficacy, safety, and tolerability of the investigational, oral, allosteric, highly selective, and potent tyrosine kinase 2 inhibitor zasocitinib (TAK-279) in patients with active psoriatic arthritis (PsA). METHODS:In this phase 2b, randomised, multicentre, double-blind, placebo-controlled, multiple-dose study, patients (≥18 years, with PsA symptoms for ≥6 months) received 30 mg, 15 mg, or 5 mg zasocitinib or placebo (1:1:1:1) once daily for 12 weeks, with a 4-week safety follow-up. The primary endpoint was American College of Rheumatology (ACR)20 response at week 12. Secondary efficacy endpoints included ACR50 response, ACR70 response, Psoriasis Area and Severity Index (PASI) 75 response among those with ≥3% body surface area at baseline and minimal disease activity (MDA) at week 12. RESULTS:Overall, 290 patients (mean [SD] age, 49.9 [11.6] years; 57.2% female) received treatment. At week 12, 30 mg or 15 mg zasocitinib treatment resulted in significantly higher ACR20 responses (54.2%; P = .002 and 53.3%; P = .002, respectively) than placebo (29.2%). A numerically higher number of ACR50 responses were achieved at week 12 with 30 mg (26.4%; nominal P = .009) or 15 mg (26.7%; nominal P = .005) zasocitinib than placebo (9.7%). In addition, 30 mg zasocitinib demonstrated a numerically higher number of ACR70 responses (13.9% versus 5.6%, respectively; nominal P = .158), PASI 75 responses (45.7% versus 15.4%, respectively; nominal P = .002), and MDA (29.2% versus 12.5%, respectively; nominal P = .014) at week 12 versus placebo. In this small study of limited duration, most adverse events were mild/moderate and were more frequently observed in the higher dose group. In this small sample size, no new safety signals or clear dose-dependent laboratory parameter changes were identified. CONCLUSIONS:Here, 30 mg and 15 mg zasocitinib demonstrated efficacy across core domains in patients with active PsA with no new safety signals. These findings will be confirmed in ongoing larger studies of longer duration.

ObjectiveThe aim of this study was to evaluate the efficacy and safety of intravenous (IV) secukinumab in patients with active psoriatic arthritis (PsA). MethodsINVIGORATE-2 (NCT04209205) was a randomized, placebo-controlled, phase 3 trial. Patients with active PsA were randomized 1:1 to receive IV secukinumab (6 mg/kg at baseline followed by 3 mg/kg every four weeks [q4w]) or placebo. At week 16, patients randomized to placebo were switched to IV secukinumab (3 mg/kg q4w), and patients who received IV secukinumab continued treatment through week 52. The primary efficacy endpoint was achievement of 50% improvement in American College of Rheumatology response criteria (ACR50) at week 16. Efficacy and safety were evaluated through weeks 52 and 60, respectively. ResultsAmong 191 patients randomized to IV secukinumab and 190 to placebo/IV secukinumab, 177 (92.7%) and 170 (89.5%) completed the entire study period, respectively. A significantly higher proportion of patients who received IV secukinumab versus placebo achieved ACR50 at week 16 (31.4% vs 6.3%; adjusted P < 0.0001). All secondary efficacy endpoints were met at week 16 (all adjusted P < 0.05 using the predefined hypothesis-testing hierarchy). Patients who switched from placebo to secukinumab at week 16 showed rapid improvements in ACR50 rates; by week 52, both treatment arms experienced similar improvements in efficacy outcomes. No new or unexpected safety signals were observed with receiving IV secukinumab. One death was reported in the placebo group before week 16. ConclusionIV secukinumab led to rapid and sustained improvements in clinical measures of PsA, and the safety profile was consistent with that of secukinumab administered subcutaneously.

Objective. Our goal was to assess the efficacy and safety of intravenous (IV) secukinumab for the treatment of adults with active axial spondyloarthritis (axSpA) in INVIGORATE-1. Methods. INVIGORATE-1 (NCT04156620) was a randomized, double-blind, parallel-group, phase 3 trial in patients with active axSpA (either radiographic or nonradiographic). Patients were randomized one to one to receive IV secukinumab (6 mg/kg at baseline followed by 3 mg/kg every four weeks) or IV placebo for 16 weeks. After week 16, patients randomized to placebo were switched to IV secukinumab (3 mg/kg every four weeks), and patients randomized to secukinumab continued treatment through week 52. The primary endpoint was the Assessment of SpondyloArthritis International Society (ASAS40) response at week 16. Safety was evaluated through week 60. Results. Among patients initially randomized to IV secukinumab (n = 264) or placebo (n = 262), 86.0% and 88.9% completed the entire 60-week study period, respectively. A higher proportion of patients receiving secukinumab versus placebo met the primary endpoint (ASAS40 response) at week 16 (40.9% vs 22.9%; P < 0.0001). By week 24, patients who switched from placebo to secukinumab at week 16 achieved ASAS40 response rates comparable to those in patients originally randomized to secukinumab. All secondary efficacy endpoints were met at week 16, and responses were sustained through week 52. No new or unexpected safety signals were observed with IV secukinumab. Conclusion. IV secukinumab was effective for the treatment of adults with active axSpA over 52 weeks. The safety profile was consistent with that in previous reports on subcutaneous secukinumab.

Anabolic therapies, recommended for patients at very high fracture risk, are administered subcutaneously (SC). The objective of this study was to evaluate the efficacy and safety of the abaloparatide microstructured transdermal system (abaloparatide-sMTS) as an alternative to the SC formulation. This phase 3, noninferiority study (NCT04064411) randomly assigned postmenopausal women with osteoporosis (N = 511) 1:1 to open-label abaloparatide administered daily via abaloparatide-sMTS or SC injection for 12 months. The primary comparison between treatment groups was the percentage change in lumbar spine bone mineral density (BMD) at 12 months, with a noninferiority margin of 2.0%. Secondary endpoints included percentage change in total hip and femoral neck BMD, bone turnover markers, dermatologic safety, and new clinical fracture incidence. At 12 months, percentage increase from baseline in lumbar spine BMD was 7.14% (SE: 0.46%) for abaloparatide-sMTS and 10.86% (SE: 0.48%) for abaloparatide-SC (treatment difference: -3.72% [95% confidence interval: -5.01%, -2.43%]). Percentage change in total hip BMD was 1.97% for abaloparatide-sMTS and 3.70% for abaloparatide-SC. Median changes from baseline at 12 months in serum procollagen type I N-terminal propeptide (s-PINP) were 52.6% for abaloparatide-sMTS and 74.5% for abaloparatide-SC. Administration site reactions were the most frequently reported adverse events (abaloparatide-sMTS, 94.4%; abaloparatide-SC, 70.5%). Incidence of serious adverse events was similar between groups. Mild or moderate skin reactions occurred with abaloparatide-sMTS with no identifiable risk factors for sensitization reactions. Few new clinical fractures occurred in either group. Noninferiority of abaloparatide-sMTS to abaloparatide-SC for percentage change in spine BMD at 12 months was not demonstrated; however, clinically meaningful increases from baseline in lumbar spine and total hip BMD were observed in both treatment groups. © 2023 Radius Health, Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

ObjectiveTo evaluate secukinumab (SEC) 300 mg and 150 mg vs placebo in a United States–only population of biologic-naïve patients with psoriatic arthritis (PsA).MethodsCHOICE was a double-blind, randomized controlled trial conducted in the US. Biologic-naïve patients with PsA and psoriasis (PsO) were randomized 2:2:1 to SEC 300 mg (n = 103), SEC 150 mg (n = 103), or placebo (n = 52). The primary objective was to show superiority of SEC 300 mg vs placebo in American College of Rheumatology 20% (ACR20) response at week 16. Additional objectives included the effect of SEC on dactylitis, enthesitis, PsO, and safety.ResultsACR20 response rates at week 16 were higher with SEC 300 mg than with placebo (51.5% vs 23.1%; odds ratio 3.51 [95% CI 1.65-7.45]; P = 0.001). SEC 300 mg also led to greater ACR50/70 responses and improvements in other variables vs placebo. Responses were generally sustained over time. Patients with inadequate response to SEC 150 mg at weeks 16, 28, or 40 who received dose escalation to 300 mg experienced improved clinical response after uptitration. The most common adverse events were upper respiratory tract infections and diarrhea. No inflammatory bowel disease was reported or new safety signals observed.ConclusionSEC 300 mg led to rapid and significant improvements over placebo in symptoms of PsA in this heavier population of US-only, biologic-naïve patients. Findings were consistent with previous studies and suggest that SEC 300 mg is a safe and efficacious first-line biologic treatment for patients with PsA. [ClinicalTrials.gov: NCT02798211]

Background Nonlinear associations in rheumatoid arthritis (RA) prevalence and sociodemographic indices suggest social determinants of health affect RA. 1 RA screening tools have lower sensitivity and specificity for Hispanic/Latinx individuals compared with white individuals (77% vs 85% sensitivity and 45% vs 87% specificity). 2 Hispanic/Latinx people also present to physicians later and with more severe RA. 3 There is little research in this population to explain these differences or how they can be addressed. Because it is known the Hispanic/Latinx population has lower English-language proficiency, we hypothesized this is in part because of the lack of validated Spanish-language educational materials and research tools for RA. Objectives To validate a Spanish-language patient-provider questionnaire (PPQ) for Hispanic/Latinx patients with RA that had previously been validated as concordant for primary care visits in Sweden. 4 To understand if rheumatologist and patient assessments for Hispanic/Latinx people with RA are concordant when using a Spanish-language digital PPQ. To determine if a Spanish-language rheumatologist-completed PPQ could be a proxy for patient impressions in a prospective clinical study. Methods A Spanish-language PPQ for RA was created by translating 9 of 13 questions previously validated in the Swedish study, 4 and adding a question about treating to target specific to RA. The survey was made available on tablet devices in 4 rheumatology clinics in the U.S. and Puerto Rico. Clinic staff obtained patient consent and gathered demographic information to generate a unique confidential identifier code for each visit, which was inputted into surveys on tablet devices. After the visit ended the patient and rheumatologist were each given the PPQ coded for that visit to complete independently of one another. The PPQs were submitted electronically to a secure database in which the visit code was the only identifier recorded. Results Across 114 clinical visits, 96.75% of possible answers were recorded and were almost invariably positive with scores of 5 (strongly agree; 88%), 4 (agree; 12%), or 3 (neither agree nor disagree; 0.09%). Physicians responded with 4 (agree) more often than patients (18% vs 6% of responses). Responses from both patient and physician were available for (96.64%) of answered questions. Within these paired answers, 80.67% were concordant (same answer from both patient and physician). Physicians answered 4 when patients answered 5 in 76.5% of discordant responses (different ratings from patient and physician). Most physician ratings of 4 came from 1 of the 4 physicians involved and only 12.5% of patients were responsible for 75% of the patient responses of 4. Conclusion Hispanic/Latinx patients with RA and their rheumatologist rated their communication, goal setting, and relationships extremely positively, making it difficult to evaluate true concordance and not possible to use rheumatologist-completed PPQs as proxy for patient assessments. Notably, ratings were substantially different from what is typically seen on Likert scales, which normally skew positively but with a normal distribution. This finding may reflect social determinants of health or cultural differences such as a social-desirability bias toward positive statements about physician-patient interactions. Heterogeneity within the participants is also a plausible explanation, considering that a distinct subset of respondents account for almost all responses below the 5 rating. Further research is needed to identify best practices for measuring treatment to target and patient-rheumatologist interactions in the Hispanic/Latinx population with RA. References [1]Safiri S, et al. Ann Rheum Dis. 2019;78(11):1463-71. doi:10.1136/annrheumdis-2019-215920 [2]Potter J, et al. J Rheumatol. 2008;35(8):1545-9. PMID: 18597406 [3]Riad M, et al. J Clin Rheumatol. 2019. doi:10.1097/RHU.0000000000001085 [4]Ahlén GC, et al. Fam Pract. 2007;24(5):498503. doi.org/10.1093/fampra/cmm043 Acknowledgements We wish to acknowledge the important contributions of our HOPE CAPE RA participants, including the patients and providers and Anne Sydor, PhD for her invaluable advice and help throughout the project. This project was funded by the Bristol Myers Squibb Foundation. Disclosure of Interests Daniel Hernandez Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, Julio Bravo Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, Juan Jose Maya Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, Oscar Soto-Raíces Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, Angel Tapia Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, Guillermo Valenzuela Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, W. Benjamin Nowell Grant/research support from: This research was supported by the Bristol Myers Squibb Foundation, Shilpa Venkatachalam Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation