Background: Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, achieved significantly greater improvements in efficacy outcomes at Week (Wk) 16 vs placebo (PBO) and sustained efficacy to Wk 52 in two phase 3 studies in patients (pts) with psoriatic arthritis (PsA).[1,2] Due to the chronic, long-term nature of PsA, sustaining high levels of disease control with treatment is important, and assessing long-term maintenance of response in pts achieving early treatment targets is of interest. Objectives: To report the proportion of Wk 16 responders maintaining their response at Wk 52, or demonstrating no loss of response at all visits to Wk 52, for joint and skin efficacy outcomes in pts with PsA from two phase 3 studies. Methods: Two phase 3 trials assessed BKZ 160 mg every 4 weeks (Q4W) in pts with PsA: BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD-naïve]; NCT03895203) and BE COMPLETE (tumour necrosis factor inhibitor intolerance/inadequate response [TNFi-IR]; NCT03896581). Both were PBO-controlled to Wk 16. BE OPTIMAL Wk 52 and BE COMPLETE Wk 16 completers could enrol in BE VITAL (open-label extension; NCT04009499). BE COMPLETE plus BE VITAL is referred to as ‘BE COMPLETE’ hereafter.Data are reported for pts randomised to BKZ at baseline (BL). Efficacy outcomes include ≥20/50/70% improvement from BL in American College of Rheumatology (ACR20/50/70) and ≥90/100% improvement from BL in Psoriasis Area and Severity Index (PASI90/100). Maintenance of response is defined as pts who achieved a response at Wk 16 and maintained that response at Wk 52. No loss of response is defined as pts who achieved a response at Wk 16 and all subsequent visits to Wk 52. Number of visits after Wk 16 varied by study and outcome (7 for ACR and 4 for PASI in BE OPTIMAL; 3 for ACR and PASI in BE COMPLETE); no loss of response data may appear higher for outcomes with fewer visits. Data are reported using non-responder imputation (NRI). Results: Of the pts randomised to BKZ, 388/431 (90.0%) bDMARD-naïve and 236/267 (88.4%) TNFi-IR pts completed Wk 52.High proportions of patients achieving ACR50 and PASI90 at Wk 16 maintained responses at Wk 52. At Wk 16, ACR50 was achieved by 189 (43.9%) bDMARD-naïve and 116 (43.4%) TNFi-IR pts; of those, 164 (86.8%) bDMARD-naïve and 93 (80.2%) TNFi-IR pts maintained response at Wk 52. Similarly, for pts with BL psoriasis affecting ≥3% body surface area, 133/217 (61.3%) bDMARD-naïve and 121/176 (68.8%) TNFi-IR pts achieved PASI90 at Wk 16; of those, 110 (82.7%) bDMARD-naïve and 107 (88.4%) TNFi-IR pts maintained response at Wk 52. The majority of pts also did not lose response at any visit to Wk 52: 110/189 (58.2%) bDMARD-naïve and 74/116 (63.8%) TNFi-IR pts did not lose ACR50 response, and 97/133 (72.9%) bDMARD-naïve and 96/121 (79.3%) TNFi-IR pts did not lose PASI90 response at any visit to Wk 52 (Figure 1).Many Wk 16 ACR70 and PASI100 responders never lost response, with the majority achieving good efficacy response (ACR50/70 or PASI90/100) at every timepoint to Wk 52 (Figure 2). At Wk 16, 105 (24.4%) bDMARD-naïve and 71 (26.6%) TNFi-IR pts achieved ACR70; of those, 87 (82.9%) bDMARD-naïve and 59 (83.1%) TNFi-IR pts maintained ACR70 response at Wk 52, and 51 (48.6%) bDMARD-naïve and 41 (57.7%) TNFi-IR pts never lost response to Wk 52. PASI100 was achieved at Wk 16 by 103/217 (47.5%) bDMARD-naïve and 103/176 (58.5%) TNFi-IR pts; of those, 82 (79.6%) bDMARD-naïve and 87 (84.5%) TNFi-IR pts maintained the response at Wk 52, and 63 (61.2%) bDMARD-naïve and 76 (73.8%) TNFi-IR pts never lost response to Wk 52. Similar trends were seen for Wk 16 ACR50 responders never losing ACR50 or ACR20 response to Wk 52 (Figure 2). Conclusion: With BKZ treatment, high proportions of Wk 16 responders maintained robust efficacy responses at Wk 52 or did not lose response at any time point to Wk 52 across joint and skin outcomes, demonstrating durable improvement irrespective of prior bDMARD use. REFERENCES: [1] Ritchlin CT. Ann Rheum Dis 2023;82:1404–14.[2] Coates LC. Ann Rheum Dis 2023;82:346–7. Acknowledgements: Funded by UCB Pharma. Medical writing support provided by Costello Medical and funded by UCB Pharma. Disclosure of Interests: William Tillett Research grants, consulting fees, speaking fees and/or honoraria from AbbVie, Amgen Inc., BMS, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ono Pharma, Pfizer and UCB Pharma, Yoshiya Tanaka Speaking fees and/or honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho and Taisho, Received grants from Chugai, Eisai, Mitsubishi-Tanabe and Taisho, Diamant Thaçi Investigator and/or consultant/advisor for AbbVie, Almirall, Amgen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly and Company, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oreal, New Bridge, Novartis, Pfizer, Regeneron, Sanofi, Target-RWE and UCB Pharma, Received grants from AbbVie, LEO Pharma and Novartis, Barbara Ink Shareholder of AbbVie, GSK and UCB Pharma, Employee of UCB Pharma, Vanessa Taieb Shareholder of UCB Pharma, Employee of UCB Pharma, Heather Edens Shareholder of UCB Pharma, Employee of UCB Pharma, Rajan Bajracharya Shareholder of UCB Pharma, Employee of UCB Pharma, Jessica A. Walsh Consultant for/grant support from AbbVie, Amgen, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB Pharma

Introduction Le bimekizumab (BKZ), un anticorps monoclonal IgG1 qui inhibe l’IL-17F en plus de l’IL-17A, a démontré son efficacité à la semaine (S)16, qui s’est maintenue jusqu’à S52, chez les patients (pts) atteints de rhumatisme psoriasique (RhuPso)[1], [2]. Nous présentons la proportion de pts répondeurs à S16 qui ont maintenu la réponse à 2ans chez les pts atteints de RhuPso et traités par BKZ. Patients et méthodes Les essais de phase III BE OPTIMAL (pts naïfs de biologique ; NCT03895203) et BE COMPLETE (pts avec réponse inadéquate ou intolérance aux anti-TNF [anti-TNF-IR] ; NCT03896581) ont évalué le BKZ à 160mg/4S chez des pts atteints de RhuPso ; les deux essais ont été contrôlés par placebo (PBO) jusqu’à S16. Les pts ayant terminé l’étude BE OPTIMAL à S52/BE COMPLETE à S16 pouvaient entrer dans l’étude d’extension en ouvert BE VITAL (NCT04009499). Les données d’efficacité sont rapportées pour les pts randomisés sous BKZ et celles de tolérance pour tous les pts traités par BKZ.Le maintien de la réponse est indiqué en pourcentage de pts répondeurs à S16 qui ont maintenu cette réponse à S104/100 (BE OPTIMAL/BE COMPLETE) ; ces résultats d’efficacité incluent les scores ACR 20/50/70, PASI 75/90/100, MDA (activité minimale de la maladie)/VLDA (très faible activité de la maladie) et DAPSA (REM (rémission)≤4 ; REM+LDA (faible activité de la maladie)≤14).L’imputation des non-répondeurs (NRI), la méthodologie des cas observés (OC) ou de la catégorie la plus défavorable ont été utilisées. Les taux d’incidence ajustés en fonction de l’exposition pour 100 pts-années (EAIR/100 PA) ont été rapportés à S104 pour les deux études. Résultats 359/431 (83,3 %) pts naïfs de biologique et 215/267 (80,5 %) pts anti-TNF-IR randomisés sous BKZ ont terminé la S104/100.Des proportions élevées de pts ayant obtenu une ACR50, un PASI100 et une MDA à S16 ont maintenu leurs réponses à S104/100 (Figure 1, Tableau 1). À S16, 189 (43,9 %) pts naïfs de biologique et 115 (43,1 %) pts anti-TNF-IR ont atteint l’ACR50 ; parmi eux, 150 (79,4 %) pts naïfs de biologique et 87 (75,7 %) pts anti-TNF-IR ont maintenu leur réponse à S104/S100. Chez les pts présentant un psoriasis initial affectant ≥3 % de la surface corporelle, 103/217 (47,5 %) pts naïfs de biologique et 103/176 (58,5 %) pts anti-TNF-IR ont atteint le PASI100 à S16 ; parmi eux, 73 (70,9 %) pts naïfs de biologique et 83 (80,6 %) pts anti-TNF-IR ont maintenu leur réponse à S104/S100. La MDA a été atteinte par 194 (45,0 %) pts naïfs de biologique et 117 (43,8 %) pts anti-TNF-IR à la S16 ; parmi eux, 147 (75,8 %) pts naïfs de biologique et 87 (74,4 %) pts anti-TNF-IR ont maintenu leur réponse à S104/S100. Des résultats similaires ont été observés pour les autres critères d’efficacité à S104/S100 (Tableau 1).À S104, le taux d’incidence ajusté en fonction de l’exposition pour 100 pts-années chez les pts traités par BKZ naïfs de biologique ou anti-TNF-IR avec≥1 était de 179,9/100,3. Conclusion Le BKZ a démontré un maintien robuste de la réponse à 2ans chez les pts atteints de RhuPso naïfs de biologique ou anti-TNF-IR ayant répondu au traitement par BKZ à S16. Le profil de tolérance était cohérent avec les rapports précédents[1], [2].

Background: Guselkumab (GUS), a fully human interleukin (IL)-23p19-subunit inhibitor, has demonstrated significant and durable efficacy and high rates of patient retention in randomized controlled trials of adults with active psoriatic arthritis (PsA).[1,2] A recent analysis of United States (US) health plan claims data showed persistence of on-label GUS (i.e., following US Food and Drug administration [FDA]-approved dosing of 100 mg administered by subcutaneous [SC] injection at Week [W] 0, W4, Q8W) at 12 months to be ~3x that of a first SC tumor necrosis factor inhibitor (TNFi).[3] Evidence in real-world adults with active PsA is also needed to compare on-label treatment persistence between patients who initiate GUS versus a first SC IL-17A inhibitor (IL-17Ai). Objectives: To compare the on-label treatment persistence in patients with PsA receiving GUS versus SC IL-17Ai. Methods: Biologic-naïve and biologic-experienced adults with active PsA, defined by ≥2 claims with a PsA diagnosis (International Classification of Diseases, 10th Revision, Clinical Modification L40.5x) ≥30 days apart within 12 consecutive months before or on the index date (the first claim/start of treatment), and ≥1 claim for GUS or first SC IL-17Ai (ixekizumab or secukinumab) between 7/14/2020–6/30/2022 were identified in IQVIA PharMetrics® Plus. Selected patients also had ≥12 months of continuous enrollment and no claim for a potentially confounding rheumatic disease within 12 months preceding the index date (Figure 1). Baseline patient characteristics were balanced between the GUS and SC IL-17Ai cohorts using propensity score (standardized mortality ratio) weighting. On-label persistence (absence of discontinuation or dose escalation/reduction relative to FDA prescribing information) was described and compared using Kaplan-Meier survival analysis and Cox proportional hazard models in the weighted treatment cohorts. Results: The GUS and SC IL-17Ai cohorts included 910 (mean age 50 years, 60% female) and 2,743 (50 years, 58% female) patients, respectively. After weighting, baseline characteristics were well-balanced, with mean follow-up of 13.5–13.7 months and 52% of patients across cohorts having received biologics in the previous 12 months. Respective rates of treatment persistence at 3, 6, 9, and 12 months were 90%, 80%, 71%, and 67% for GUS versus 81%, 67%, 57%, and 50% for SC IL-17Ai (overall log-rank p<0.001). Patients in the GUS cohort were significantly more likely than those in the SC IL-17Ai cohort to remain persistent on treatment at each timepoint assessed, with increasing hazard ratios (HR) from 3 to 12 months (HR=1.85; p<0.001; Figure 2). Median time to discontinuation was not reached for GUS and was 12.3 months for SC IL-17Ai. Conclusion: In this real-world study employing primarily commercial US health plan claims data to assess on-label treatment persistence in patients with PsA, GUS was associated with a significantly greater (nearly 2x) likelihood of persistence at 12 months compared with an initial SC IL-17Ai. REFERENCES: [1] Ritchlin CT. RMD Open. 2021;7:e001457.[2] McInnes IB. Arthritis Rheumatol. 2022;74:475-85.[3] Walsh J. Comparison of On-label Treatment Persistence in Real-world Patents With PsA Receiving Guselkumab Versus Subcutaneous TNF Inhibitors. Poster presented at: CCR-W; 2023; San Diego, CA. Acknowledgements: NIL. Disclosure of Interests: Natalie J. Shiff Owns or has owned stock in AbbVie, Gilead, Iovance, Johnson & Johnson, Novo-Nordisk, and Pfizer within the past 3 years. [Current stock ownership: AbbVie, Gilead, Iovance, Jazz, Johnson & Johnson, Novavax, and Viatris], Employee of Janssen Scientific Affairs, LLC; received salary support from the Childhood Arthritis and Rheumatology Research Alliance within the past 3 years, Philip J. Mease Speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consulting fees from AbbVie, Acelyrin, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Immagene, Janssen, Novartis, Pfizer, SUN, UCB, and Ventyx, Research grants from AbbVie, Acelyrin, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, SUN, and UCB, Ruizhi Zhao Owns stock in Johnson & Johnson, Former employee of Janssen Scientific Affairs, LLC, Shannon Ferrante Owns stock in Johnson & Johnson, Employee of Janssen Scientific Affairs, LLC, Soumya D. Chakravarty Owns stock in Johnson & Johnson, Employee of Janssen Scientific Affairs, LLC, Jessica A. Walsh Consulting for AbbVie, Eli Lilly, Janssen, Novartis, and UCB, Research funding from AbbVie, Merck, and PfizerFigure 1Data source and study design Figure 2Kaplan-Meier analysis of on-labela persistenceb in propesnity score weightedc GUS and SC IL-17Ai cohorts

Background: In psoriatic arthritis (PsA), treatment persistence is important for achieving optimal outcomes. The United States Food and Drug Administration (USFDA) approved guselkumab (a fully human interleukin [IL]-23p19-subunit inhibitor) for the treatment of active PsA in July 2020. Objectives: To provide real-world evidence comparing treatment persistence while following USFDA prescribing guidelines (i.e., on-label persistence) for guselkumab (100 mg administered by subcutaneous [SC] injection at Week [W] 0, W4, then Q8W) versus SC tumor necrosis factor inhibitors (TNFi). Methods: Adults with PsA newly initiated on guselkumab or the first observed SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or SC golimumab) between 7/14/2020 and 3/31/2022 were selected from the IQVIATM Health Plan Claims Data. The first claim for guselkumab or a SC TNFi was defined as the index date; study cohorts included bio-naïve and bio-experienced patients. Baseline characteristics were assessed during the 12-month pre-index period; the follow-up period spanned from the index date until the earliest date between the end of the continuous insurance eligibility and the end of data availability (09/30/2022; Figure 1). On-label persistence of the index agent was defined as the absence of treatment discontinuation or any dose escalation/reduction relative to the USFDA label dosing instructions for each respective agent. Discontinuation was defined as having a gap in treatment between consecutive days of the index agent supply of twice the duration of days of supply for a claim (i.e., 2 x 56 = 112 days for guselkumab or 2 x 28 = 56 days for SC TNFi) during follow-up. Patients with any dose change were censored on the first observed date of the dose change. Guselkumab and SC TNFi cohorts were balanced for baseline characteristics, using propensity score weighting based on the standardized mortality ratio (SMR) weighting approach. On-label persistence was assessed using weighted Kaplan-Meier (KM) curves. A weighted Cox proportional hazards model, further adjusted for baseline biologic use, was used to compare on-label persistence between cohorts. Results: The guselkumab cohort included 526 patients (mean age: 49.8 years; 61.2% female) and the SC TNFi cohort included 1,953 patients (mean age: 48.5 years; 60.2% female). After IPTW, baseline characteristics were well balanced and the mean follow-up was 12.3 months for the guselkumab cohort and 12.4 months for the SC TNFi cohort. In the guselkumab cohort, 51.5% were bio-experienced versus 16.7% for SC TNFi. Median time to discontinuation was not reached for the guselkumab cohort versus 8.9 months for the SC TNFi cohort. Weighted KM rates of on-label persistence at 3, 6, 9, and 12 months were 91.2%, 84.1%, 75.9%, and 71.5%, for the guselkumab cohort, versus 77.3%, 61.6%, 50.0%, and 43.7%, for the SC TNFi cohort, respectively (all log-rank p<0.001). At 12 months, patients in the guselkumab cohort were approximately three times more likely to remain persistent on treatment than patients in the SC TNFi cohort (hazard ratio: 2.97; 95% confidence interval: 2.36-3.74; p<0.001; Figure 2). Conclusion: This real-world study assessing treatment persistence in PsA using administrative claims data demonstrated that guselkumab was associated with significantly longer on-label persistence through 12 months versus SC TNFi. Acknowledgements: NIL. Disclosure of Interests: Natalie J. Shiff Stockholder of Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary, Employee of Janssen Scientific Affairs, LLC, Jessica A. Walsh Consultant for AbbVie, Janssen, Eli Lilly, Novartis, and UCB, Research funding from Pfizer, Merck, AbbVie, Iris Lin Stockholder of Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary, Employee of Janssen Scientific Affairs, LLC, Ruizhi Zhao Stockholder of Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary, Employee of Janssen Scientific Affairs, LLC, Laura Morrison Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Bruno Emond Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Louise H. Yu Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Samuel Schwartzbein Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Patrick Lefebvre Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Dominic Pilon Employee of Analysis Group, Inc., a consulting company that has received research funding from Janssen Scientific Affairs, LLC, Soumya D. Chakravarty Stockholder of Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary, Employee of Janssen Scientific Affairs, LLC, Philip J. Mease Speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant for AbbVie, Acelyrin, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, UCB, and Ventyx, Research funding from AbbVie, Acelyrin, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB.

Discontinuation of biologic disease-modifying anti-rheumatic drugs (bDMARDs) is common and associated with poor clinical outcomes in ankylosing spondylitis (AS). We assessed bDMARD persistence, factors associated with bDMARD discontinuation, and dosing patterns in patients with AS using IBM® MarketScan® US claims databases.

Background Involvement of weight-bearing joints in patients with psoriatic arthritis (PsA) can be associated with reduced activities of daily living and quality of life. Upadacitinib (UPA) is an oral, reversible Janus kinase inhibitor approved for the treatment of active PsA in adults. In the SELECT-PsA 1 and SELECT-PsA 2 trials, treatment with once daily UPA 15 mg (UPA15) or 30 mg (UPA30) resulted in greater improvements in the number of swollen and tender joints as well as other patient- and physician-reported outcomes when compared with placebo.[1-3] Objectives To evaluate the long-term efficacy of UPA in patients with PsA and involvement in 1 or more regions of weight-bearing joints. Methods The SELECT-PsA 1 (NCT03104400) and SELECT-PsA 2 (NCT03104374) phase 3, randomized, controlled trials enrolled patients ≥ 18 years old with active PsA and intolerance or inadequate response to ≥ 1 nonbiologic disease modifying anti-rheumatic drug (DMARD; SELECT-PsA 1) or biologic DMARD (SELECT-PsA 2). This post hoc analysis of the 2 phase 3 trials stratified patients with involvement in 1 to 6 regions of weight-bearing joints (hips, knees, ankles, midfoot, metatarsophalangeal [MTP], or proximal interphalangeal [PIP]) who were randomized at baseline to receive either UPA15, placebo (PBO), or adalimumab (ADA; only in SELECT-PsA 1); at week 24, PBO-treated patients switched to UPA15 (PBO/UPA15). This analysis did not include patients who received UPA30 or PBO/UPA30. A mixed-effects model with repeated measures was used to analyze the change from baseline to week 104 in 4 patient-reported outcome measures (pain, Health Assessment Questionnaire-Disability Index [HAQ-DI], Work Productivity and Activity Impairment [WPAI] questionnaire, and EuroQol 5 Dimension 5 Level [EQ-5D-5L]) and 1 composite outcome measure (Disease Activity in Psoriatic Arthritis [DAPSA]). UPA safety results in patients with PsA have been previously reported.[1-3] Results A total of 1069 patients from the SELECT-PsA 1 trial and 317 patients from the SELECT-PsA 2 trial were included in the pooled analysis. Of all patients with any involvement in regions of weight-bearing joints, > 91% of patients had involvement in ≥ 2 regions. The most common weight-bearing joints with involvement were the PIP (SELECT-PsA 1, 79.8%; SELECT-PsA 2, 84.5%), MTP (71.1%; 73.8%), and knee (62.3%; 64.9%) joints. Improvements from baseline to week 104 were observed with UPA15 treatment in patient-reported outcomes of pain, HAQ-DI, WPAI, EQ-5D-5L, and the DAPSA score across all subgroups of patients with involvement in 1 to 6 regions of weight-bearing joints (Figure 1). In general, the magnitude of improvement in outcome scores with UPA15 was greater in patients with involvement in a higher number of regions. Similar improvements from baseline to week 104 in outcome scores were observed in patients who received PBO/UPA15 or ADA to week 104. Conclusion UPA15 treatment was associated with long-term improvements in pain, disability, work productivity, disease activity, and quality of life in patients with PsA and involvement in 1 or more regions of weight-bearing joints. References [1]McInnes IB, et al. N Engl J Med. 2021;384:1227–1239. [2]McInnes IB, et al. RMD Open. 2021;7:e001838. [3]Mease PJ, et al. Ann Rheum Dis. 2022;80:312–320. Acknowledgements AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approving the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. All authors agreed to submit this abstract to the EULAR 2023 Congress. Medical writing support was provided by Michael Dyle, PhD, of JB Ashtin, and funded by AbbVie. Disclosure of Interests Kristi Mizelle Speakers bureau: AbbVie, Amgen, Eli Lilly, GSK, Janssen, and Pfizer, Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, and UCB, William Tillett Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ono-Pharma, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, GSK, Janssen, and Pfizer, Mira Ali Shareholder of: May hold stock or stock options for AbbVie, Employee of: AbbVie, Thomas Iyile Shareholder of: May hold stock or stock options for AbbVie, Employee of: AbbVie, Tianming Gao Shareholder of: May hold stock or stock options for AbbVie, Employee of: AbbVie, Arathi Setty Shareholder of: May hold stock or stock options for AbbVie, Employee of: AbbVie, Jessica A. Walsh Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, Merck, and Pfizer, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

Seven participants were interviewed to uncover how they remain so productive in their wisdom years, those typically marked by retirement. Participants included a leading educational psychologist, a renowned national television news anchor, a four-time national champion collegiate coach, the founder and former chief executive of Arbor Day Foundation, a university scholar turned playwright, and two female adventurers who quit their jobs, sold their possessions, and have lived a nomadic life, hiking thousands of miles throughout America. Their wisdom years stories describe how and why they shun retirement and remain productive. The article concludes with seven advice-laden conclusions for readers: (a) Do not retire, but if you do, retire to something, (b) follow your bliss, (c) work hard, (d) offset aging challenges, (e) be inspired by role models, (f) be a life-long learner, and (g) take heed of the universe conspiring.

Background The multiple joint and skin manifestations of psoriatic arthritis (PsA) place a substantial burden on patient quality of life.[1] Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. Objectives To examine the association between achieving increasingly stringent clinical disease control criteria and patient-reported measures of physical function, pain and fatigue in patients (pts) with PsA, using Week (Wk) 52 data from BE OPTIMAL. Methods BE OPTIMAL (NCT03895203) comprised a 16-wk double-blind placebo (PBO)-controlled period and a 36-wk treatment blind period. Pts were ≥18 years, biologic disease-modifying antirheumatic drug naïve, with adult-onset, active PsA, ≥3 tender and ≥3 swollen joints. Pts were randomised 3:2:1, subcutaneous BKZ 160 mg every 4 weeks (Q4W):PBO:reference arm (adalimumab 40 mg Q2W). From Wk 16, PBO pts received BKZ 160mg Q4W. In this post hoc analysis, all pts who reached specified disease control criteria (ACR: ACR20 not reached [<ACR20], ACR20 reached but not ACR50 [ACR20–<ACR50], ACR50 reached but not ACR70 [ACR50–<ACR70], ACR70 reached [ACR70]; ACR50 and Psoriasis Area and Severity Index 100 [ACR50+PASI100]: non-responder, responder; Disease Activity in PsA [DAPSA]: high, moderate and low disease activity or remission [HDA, MoDA and LDA/REM, respectively]; Minimal Disease Activity [MDA]: non-MDA, MDA) at Wk 52 were pooled regardless of treatment arm. Associations between achieving these criteria and improvements in the following patient-reported physical function and symptom measures were assessed: Health Assessment Questionnaire Disability Index (HAQ-DI), Pt’s Assessment of Arthritis Pain Visual Analog Scale (Pain VAS) and Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-Fatigue). It should be noted that some aspects of the disease control criteria relate to aspects of HAQ-DI and PtAAP. Observed case data were reported. Results 821/852 (96.4%) pts completed Wk 16; 761 (89.3%) completed Wk 52. Baseline mean (SD) HAQ-DI (0 [best] to 3 [worst]), Pain VAS (0 [best] to 100 [worst]) and FACIT-Fatigue (0 [worst] to 52 [best]) scores were 0.85 (0.59), 55.2 (23.9) and 37.0 (9.7). Pts achieving higher ACR response thresholds demonstrated sequentially greater mean (95% CI) improvements from baseline in HAQ-DI, Pain VAS and FACIT-Fatigue (Figure 1). Similar improvements from baseline in HAQ-DI, Pain VAS and FACIT-Fatigue were seen with the achievement of ACR50+PASI100, increasingly stringent DAPSA thresholds and the achievement of MDA (Figure 1). Conclusion Patients with active PsA who achieved increasingly stringent disease control criteria at Wk 52 reported concomitantly greater improvements in patient-reported measures of physical function, pain and fatigue. Reference [1]Tillett W. Rheumatol Ther 2020;7(3):617–37. Acknowledgements This study was funded by UCB Pharma. Medical writing support was provided by Costello Medical, funded by UCB Pharma. Disclosure of Interests Lars Erik Kristensen Speakers bureau: AbbVie, Amgen, Biogen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Amgen, Biogen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, Novartis, Novo Nordisk, and UCB Pharma, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Pharma, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma, Joseph F. Merola Consultant of: Consultant and/or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB Pharma, Paolo Gisondi Consultant of: AbbVie, Abiogen, Almirall, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Sanofi and UCB Pharma, Peter Nash Grant/research support from: Research grants, clinical trials and honoraria for advice and lectures on behalf of AbbVie, Boehringer Ingelheim, BMS, Eli Lilly, Galapagos/Gilead, GSK, Janssen, Novartis, Pfizer, Samsung, Sanofi and UCB Pharma, Ana-Maria Orbai Consultant of: BMS, Janssen, Sanofi and UCB Pharma, Grant/research support from: Research grants to Johns Hopkins University from AbbVie, Amgen and Janssen, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB Pharma, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB Pharma, Barbara Ink Shareholder of: UCB Pharma, AbbVie and GSK, Employee of: UCB Pharma, Rajan Bajracharya Shareholder of: UCB Pharma, Employee of: UCB Pharma, Vanessa Taieb Employee of: UCB Pharma, Jérémy Lambert Shareholder of: UCB Pharma, Employee of: UCB Pharma, Damon Willems Shareholder of: UCB Pharma, Employee of: UCB Pharma, Jessica A. Walsh Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma.

BackgroundAxial spondyloarthritis (axSpA) is a chronic inflammatory disease encompassing radiographic (traditionally known as ankylosing spondylitis) and non-radiographic forms that lead to chronic pain, structural damage, and disability.1 The International Map of Axial Spondyloarthritis (IMAS) survey is an initiative developed to generate insights into the real-life experiences of people living with axSpA to ultimately improve quality of life.2ObjectivesTo assess the burden and daily experience of patients with axSpA in the United States.MethodsThe IMAS survey generates a report on patient-reported aspects of disease burden and experience with axSpA using adaptations of the original Atlas of axSpA questionnaire developed in collaboration with patients, the Axial Spondyloarthritis International Federation, and clinical academic experts. In this US adaptation of the IMAS survey, a 30-minute quantitative online survey was administered to US patients aged ≥18 years who completed screening questions, self-reported having been diagnosed with axSpA by a healthcare provider, and were under the care of a healthcare provider between July 22, 2021, and November 10, 2021. Survey questions were tailored to reflect differences in the US healthcare systems and the availability of treatments. This analysis presents a portion of the US data describing patient demographics, clinical characteristics, journey to axSpA diagnosis, and the emotional impact and overall burden of disease on quality of life using the General Health Questionnaire 12 (GHQ-12), the Assessment of SpondyloArthritis international Society – Health Index (ASAS-HI), and a global limitation index of 18 activities of daily living. All results were reported descriptively using summary statistics.ResultsSurvey data from 228 US patients with axSpA were collected in this analysis. The mean age was 45 years, 60% of patients were female, and the mean BMI was 27.7 kg/m2 (Table 1). Participating patients had an average of 5.6 comorbidities, with anxiety (43%), depression (41%), and hypertension (32%) as the most commonly reported comorbidities. Among all patients, the mean age at onset of first symptoms was 26 years and the mean age at diagnosis was 35 years; overall, mean diagnostic delay was greater in female than in male patients (11.2 vs 5.2 years; Figure 1A). According to the validated GHQ-12, over half of the patients (57%) were at risk for psychological distress (GHQ-12 score ≥3; Figure 1B). Patients who were older (>40 years old), physically inactive, or who had active disease (BASDAI ≥4) were at risk for psychological distress. Most patients (82%) suffered from a high degree of impairment (ASAS-HI ≥6), 47% had a medium or high limitation in activities of daily living, and 46% of patients were not employed at the time of the survey.Table 1.Patient Demographic and Clinical CharacteristicsCharacteristicPatients with axSpA(N=228)Mean age, years45Female, %60White, %86Mean body mass index, kg/m227.7Nonsmoker, %62Alcohol consumption behavior, %Never19Every day9Mean number of comorbidities5.6Common comorbidities (≥20% of patients), %aAnxiety43Depression41Hypertension32Obesity/overweight31Sleep disorders30Hypercholesterolemia29Uveitis24Psoriatic arthritis23Fibromyalgia20Spinal or other fractures20Psoriasis20Employed, %54axSpA, axial spondyloarthritis.aRespondents could have selected ≥1 answer.ConclusionThis study showed that a high proportion of US patients with axSpA report impaired function and are at risk for psychological distress. Patients also experienced a substantial delay in the time to axSpA diagnosis, with longer delays than those reported in the European Union. Delays were twice as long in women compared to men. These findings highlight the large impact of disease on daily activities and mental distress in US patients with axSpA.References[1]Sieper J, Poddubnyy D. Lancet. 2017;390:73-84.[2]Garrido-Cumbrera M, et al. Curr Rheumatol Rep. 2019;21:19.AcknowledgementsThis study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Medical writing support was provided by Charli Dominguez, PhD, of Health Interactions, Inc, Hamilton, NJ, USA, and was funded by Novartis Pharmaceuticals Corporation. This abstract was developed in accordance with Good Publication Practice (GPP3) guidelines. Authors had full control of the content and made the final decision on all aspects of this publication.Disclosure of InterestsMarina Magrey Consultant of: Received consulting fees from Eli Lilly and Novartis, Grant/research support from: Received research grants from AbbVie, Amgen, and UCB, Jessica A. Walsh Consultant of: Received consulting fees from Amgen, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Grant/research support from: Received research funding from AbbVie, Merck, and Pfizer, Sandra Flierl Employee of: Employee of Ipsos, Renato Calheiros Employee of: Employee of Novartis, David Wei Employee of: Employee of Novartis, Muhammad Asim Khan Consultant of: Has served as a consultant for Novartis

Il est important d’évaluer le maintien de la réponse chez les patients (pts) souffrant de rhumatisme psoriasique (RhPso), car ils peuvent avoir une perte de réponse secondaire au fil du temps [1]. Le bimékizumab (BKZ), un anticorps monoclonal IgG1 qui inhibe sélectivement l’interleukine (IL)-17F en plus de l’IL-17A, a démontré une efficacité cliniquement pertinente au niveau articulaire et cutané à la semaine (S) 16 par rapport au placebo (PBO) chez les pts atteints de RhPso [2], [3]. Les réponses ont été maintenues jusqu’à S52 [4]. Dans l’étude BE OPTIMAL, les pts naïfs de biologique ont été randomisés suivant un ratio 3:2:1, respectivement, dans les bras BKZ160 mg toutes les 4S (/4S), PBO et groupe de référence (40 mg d’adalimumab/2S). À S16, les pts sous PBO sont passés au BKZ (PBO/BKZ). Le maintien de la réponse est indiqué en pourcentage de pts traités par BKZ répondeurs à S16 qui ont maintenu cette réponse à S52. Les données sont rapportées pour les pts randomisés au BKZ à l’inclusion. Les critères d’évaluation incluent les scores ACR 20/50/70, les scores PASI 75/90/100, l’activité minimale ou très faible de la maladie (MDA/VLDA), une rémission ou une faible activité DAPSA (REM ≤ 4 et LDA ≤ 14). Pour les réponses à S16 et le maintien de celle-ci jusqu’à S52, l’imputation des non-répondeurs (NRI) a été utilisée ; l’imputation en cas observés (OC) a aussi été utilisée jusqu’à S52. Les événements indésirables apparus sous traitement (EIAT) à S52 sont rapportés pour les pts ayant reçu ≥ 1 dose de BKZ, y compris pour les pts PBO/BKZ. À l’inclusion, parmi les 431 pts randomisés sous BKZ, 217 (50,3 %) présentaient un psoriasis affectant ≥ 3 % de la surface corporelle (SC), 414 (96,1 %) ont poursuivi leur traitement jusque S16 et 388 (90,0 %) jusque S52. La majorité des pts répondeurs à S16 ont maintenu leur réponse à S52, sur l’ensemble des critères, au niveau cutané et articulaire (Fig. 1). À S16, 268 (62,2 %), 189 (43,9 %) et 105 (24,4 %) pts ont respectivement obtenu un score ACR 20/50/70. Parmi ces répondeurs, les réponses ACR 20/50/70 ont été maintenues à S52 par plus de 80 % des pts : 88,4 %, 86,8 %, 82,9 % (NRI) ; 92,9 %, 91,1 % et 87,9 % (OC). Au total, 133/217 (61,3 %) et 103/217 (47,5 %) pts atteints de psoriasis à l’inclusion ont obtenu respectivement des scores PASI 90 et100 à S16. La majorité des pts ont maintenu la réponse à S52 : 82,7 %, 79,6 % (NRI) ; 94,0 %, 89,1 % (OC). Les mesures d’efficacité composites suivent le même schéma ; 194 (45,0 %) pts ont obtenu une MDA à S16 et 85,6 % (NRI) et 90,7 % (OC) ont maintenu cette réponse à S52. De nombreux répondeurs à S16 ont également maintenu leur réponse à S52 pour la VLDA, le DAPSA REM + LDA et le DAPSA REM (Fig. 1). À S52, 555/702 (79,1 %) pts ont rapporté ≥ 1 EIAT pendant le traitement par BKZ ; 46 (6,6 %) ont signalé des EIAT graves. Le traitement par BKZ a permis à une proportion élevée de patients répondeurs à S16 de maintenir une efficacité nette à S52, évaluée par des critères articulaires, cutanés et composites. Le profil de tolérance du BKZ était cohérent avec les données connues [2], [3].

The multiple joint and skin manifestations of psoriatic arthritis (PsA) place a substantial burden on patient quality of life.[1]Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A.To examine the association between achieving increasingly stringent clinical disease control criteria and patient-reported measures of physical function, pain and fatigue in patients (pts) with PsA, using Week (Wk) 52 data from BE OPTIMAL.BE OPTIMAL (NCT03895203) comprised a 16-wk double-blind placebo (PBO)-controlled period and a 36-wk treatment blind period. Pts were ≥18 years, biologic disease-modifying antirheumatic drug naïve, with adult-onset, active PsA, ≥3 tender and ≥3 swollen joints. Pts were randomised 3:2:1, subcutaneous BKZ 160 mg every 4 weeks (Q4W):PBO:reference arm (adalimumab 40 mg Q2W). From Wk 16, PBO pts received BKZ 160mg Q4W. In this post hoc analysis, all pts who reached specified disease control criteria (ACR: ACR20 not reached [<ACR20], ACR20 reached but not ACR50 [ACR20–<ACR50], ACR50 reached but not ACR70 [ACR50–<ACR70], ACR70 reached [ACR70]; ACR50 and Psoriasis Area and Severity Index 100 [ACR50+PASI100]: non-responder, responder; Disease Activity in PsA [DAPSA]: high, moderate and low disease activity or remission [HDA, MoDA and LDA/REM, respectively]; Minimal Disease Activity [MDA]: non-MDA, MDA) at Wk 52 were pooled regardless of treatment arm. Associations between achieving these criteria and improvements in the following patient-reported physical function and symptom measures were assessed: Health Assessment Questionnaire Disability Index (HAQ-DI), Pt’s Assessment of Arthritis Pain Visual Analog Scale (Pain VAS) and Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-Fatigue). It should be noted that some aspects of the disease control criteria relate to aspects of HAQ-DI and PtAAP. Observed case data were reported.821/852 (96.4%) pts completed Wk 16; 761 (89.3%) completed Wk 52. Baseline mean (SD) HAQ-DI (0 [best] to 3 [worst]), Pain VAS (0 [best] to 100 [worst]) and FACIT-Fatigue (0 [worst] to 52 [best]) scores were 0.85 (0.59), 55.2 (23.9) and 37.0 (9.7). Pts achieving higher ACR response thresholds demonstrated sequentially greater mean (95% CI) improvements from baseline in HAQ-DI, Pain VAS and FACIT-Fatigue (Figure 1). Similar improvements from baseline in HAQ-DI, Pain VAS and FACIT-Fatigue were seen with the achievement of ACR50+PASI100, increasingly stringent DAPSA thresholds and the achievement of MDA (Figure 1).Patients with active PsA who achieved increasingly stringent disease control criteria at Wk 52 reported concomitantly greater improvements in patient-reported measures of physical function, pain and fatigue.[1]Tillett W. Rheumatol Ther 2020;7(3):617–37.This study was funded by UCB Pharma. Medical writing support was provided by Costello Medical, funded by UCB Pharma.Lars Erik Kristensen Speakers bureau: AbbVie, Amgen, Biogen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Amgen, Biogen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, Novartis, Novo Nordisk, and UCB Pharma, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Pharma, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma, Joseph F. Merola Consultant of: Consultant and/or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB Pharma, Paolo Gisondi Consultant of: AbbVie, Abiogen, Almirall, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Sanofi and UCB Pharma, Peter Nash Grant/research support from: Research grants, clinical trials and honoraria for advice and lectures on behalf of AbbVie, Boehringer Ingelheim, BMS, Eli Lilly, Galapagos/Gilead, GSK, Janssen, Novartis, Pfizer, Samsung, Sanofi and UCB Pharma, Ana-Maria Orbai Consultant of: BMS, Janssen, Sanofi and UCB Pharma, Grant/research support from: Research grants to Johns Hopkins University from AbbVie, Amgen and Janssen, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB Pharma, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB Pharma, Barbara Ink Shareholder of: UCB Pharma, AbbVie and GSK, Employee of: UCB Pharma, Rajan Bajracharya Shareholder of: UCB Pharma, Employee of: UCB Pharma, Vanessa Taieb Employee of: UCB Pharma, Jérémy Lambert Shareholder of: UCB Pharma, Employee of: UCB Pharma, Damon Willems Shareholder of: UCB Pharma, Employee of: UCB Pharma, Jessica A. Walsh Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma.

BackgroundFatigue is common in patients (pts) with ankylosing spondylitis (AS) and is associated with higher levels of pain and functional disability.1 Tofacitinib is an oral JAK inhibitor approved for the treatment of AS. In pts with AS, greater improvements in fatigue were seen with tofacitinib vs placebo (PBO).2ObjectivesTo estimate the time to improvement in fatigue in pts with AS treated with tofacitinib.MethodsThis post hoc analysis used data from a Phase 3 trial (NCT03502616) in pts with AS receiving tofacitinib 5 mg twice daily (BID) or PBO for 16 weeks; after Week (W)16, all pts received open-label tofacitinib until W48.2 Fatigue was assessed by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score (range 0–52; higher scores indicate less fatigue3). A series of time to event analyses were performed using non-parametric Kaplan–Meier models. Median times to initial improvements in FACIT-F total score were assessed based on different thresholds. The initial improvement event was defined as time to first post-baseline week with an improvement in FACIT-F total score of at least 5%, 10%, 15% etc, up to 100%. Median times to events based on absolute changes in FACIT-F total score were also investigated.ResultsOverall, 269 pts were assessed; baseline demographics/disease characteristics have been previously reported.2 The median times to initial improvements in FACIT-F total score were significantly (p<0.05) shorter in pts receiving tofacitinib 5 mg BID vs PBO (Figure 1). For example, median time to initial improvement of 30% in FACIT-F total score was 16 weeks in pts receiving tofacitinib 5 mg BID; however, in pts receiving PBO, the median time for this event was not achieved up to W16. More pts receiving tofacitinib 5 mg BID vs PBO experienced initial improvement events up to W16 (Table 1). For example, 36.1% of pts receiving tofacitinib 5 mg BID experienced 50% improvement of fatigue up to W16, compared with 19.9% of pts receiving PBO.Table 1.Proportions of pts who experienced initial improvement events in FACIT-F total score up to W16Fatigue improvement thresholdInitial improvement, n (%)p valuea25%Tofacitinib 5 mg BID82 (61.7)0.0009PBO58 (42.6)50%Tofacitinib 5 mg BID48 (36.1)0.0031PBO27 (19.9)75%Tofacitinib 5 mg BID30 (22.6)0.0626PBO19 (14.0)100%Tofacitinib 5 mg BID23 (17.3)0.1233PBO15 (11.0)N=133 (tofacitinib 5 mg BID); N=136 (PBO)aTest of equality over strata log-rank test, p<0.05 n, number of pts achieving an initial improvement event; N, total number of pts in each treatment groupConclusionIn pts with AS, initial improvements in fatigue, as determined by FACIT-F total score, occurred faster and were larger in magnitude with tofacitinib vs PBO up to W16. These results may help physicians better understand the speed and magnitude for fatigue benefit in pts receiving tofacitinib.References[1]Turan et al. Rheumatol Int 2007; 27: 847-852.[2]Deodhar et al. Ann Rheum Dis 2021; 80: 1004-1013.[3]Hewlett et al. Arthritis Care Res (Hoboken) 2011; 63: S263-286.AcknowledgementsStudy sponsored by Pfizer Inc. Medical writing support was provided by Lauren Hogarth, CMC Connect, and funded by Pfizer Inc.Disclosure of InterestsLaure Gossec Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche and UCB, David Cella Consultant of: AbbVie, Alexion Pharmaceuticals, Astellas Pharma, Bayer, Bristol-Myers Squibb, Clovis Oncology, Evidera, Exelixis, Horizon Therapeutics, Janssen, Merck/Schering-Plough, National Academy of Sciences, Novartis Pharma K.K. (Japan), Pfizer Inc, PledPharma and Regeneron, Jessica A. Walsh Consultant of: AbbVie, Celgene and UCB, Raj Sengupta: None declared, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Oluwaseyi Dina Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

La fatigue est fréquente chez les patients (pts) avec une spondylarthrite ankylosante (SA), associée à des douleurs et une incapacité fonctionnelle [1]. Le tofacitinib (tofa) est un JAK inhibiteur oral autorisé pour traiter la SA. Des améliorations plus importantes de la fatigue ont été observées avec le tofa vs placebo chez des pts SA.2 Il s’agit ici d’une analyse post-hoc afin d’estimer le délai d’amélioration de la fatigue chez les pts SA traités par tofa. Il s’agit de données d’un essai de phase 3 (NCT03502616) chez des pts SA recevant du tofa 5 mg deux fois par jour (2X/J) ou PBO pendant 16 semaines (S16) ; après 16S, tous les pts ont reçu en ouvert du tofacitinib jusqu’à S48.2 La fatigue a été évaluée par le score FACIT-F total (Functional Assessment of Chronic Illness Therapy Fatigue) (score de 0 à 52 ; des scores plus élevés indiquent moins de fatigue3). Une série d’analyse des délais de survenu des événements a été effectuée à l’aide de modèles non paramétriques de Kaplan–Meier. Les délais médians pour les améliorations du score FACIT-F ont été évaluées en fonction de différents seuils. Le premier événement d’amélioration a été défini comme le délai à partir de l’inclusion avec une amélioration du score FACIT-F d’au moins 5 %, 10 %, 15 %, etc., jusqu’à 100 %. Les délais médians aux événements basés sur les modifications absolues du score FACIT-F ont également été étudiées. Dans l’ensemble, 269 pts ont été évalués ; les caractéristiques des pts à l’inclusion ont déjà été rapportées.2 Les délais médians d’amélioration initiale du score FACIT-F étaient significativement (p < 0,05) plus courts chez les pts recevant du tofacitinib 5 mg 2X/J vs PBO ; le délai médian d’amélioration initiale de 30 % du score FACIT-F était de 16 semaines chez les pts recevant du tofa 5 mg 2X/J ; alors qu’il n’a pas été atteint par les pts recevant le PBO à S16. Plus de pts recevant du tofa 5 mg 2X/J vs PBO ont connu des événements d’amélioration jusqu’à S16 (Tableau 1) ; 36,1 % des pts recevant du tofa 5 mg 2X/J ont connu une amélioration de 50 % de la fatigue jusqu’à S16, contre 19,9 % des pts sous PBO. Chez les pts SA, les améliorations de la fatigue, telles que déterminées par le score FACIT-F, on été observé plus vite avec des seuils plus importants avec le tofa vs PBO jusqu’à S16.

Background Generating information that people living with a rheumatic and musculoskeletal disease (RMD) find useful while making decisions about their treatment requires identifying and understanding educational needs and interests directly expressed from people living with RMD. Objectives To identify what types of information US adults with RMD perceive as important to know about their disease and how they express and prioritize such information. Methods Using nominal group technique, focus groups of participants (pts) with RMD generated sets of rank-order educational items which were then aggregated across groups into themes. Based on nominal group results, a survey with the final 28 items was administered online, along with a question about desired functions of a smartphone app for RMD, to members of the ArthritisPower registry in January 2022. Results Six nominal groups (n=47) yielded 28 unique items for the online survey of educational priorities. To date, a total of 570 pts completed the survey, of whom 85.4% were female, 89.5% white, mean age of 59.6 (SD 11.2) years. Rheumatoid arthritis (52.5%), osteoarthritis (16.0%), psoriatic arthritis (12.5%), and axial spondyloarthritis (7.5%) were the most common RMDs. Knowing how to tell when a medication is not working, how RMD affects other medical conditions, understanding the results of tests used to monitor their RMD, available treatment options and possible side effects, and how life will change as an RMD progresses were each items that > 75% of pts considered extremely important (Table 1). Top functions pts listed as useful for a smartphone app included being able to participate in research, view lab results, record symptoms or flares, share how they are doing with their provider, and get educational information about their disease (Table 2). Table 1. Top Education Topics Adults with Rheumatic and Musculoskeletal Disease Consider Extremely Important (N=570). Item n (% ) Knowing when the medication is not working 505 (88.6) Knowing how a rheumatologic condition can affect your other health conditions or medical issues 481 (84.4) Understanding the results of tests used to monitor your condition 471 (82.6) Knowing the side effects of available drugs, and how the drugs interact with each other 461 (80.9) Finding the right rheumatologist 453 (79.5) Having realistic expectations of the effectiveness of the medications 445 (78.1) Knowing how the disease will progress, even if the news is bad 439 (77.0) Knowing the available medications and treatments for your rheumatologic condition 437 (76.7) Knowing how long it takes drugs to work 436 (76.5) Understanding how your life will change as your disease progresses 434 (76.1) Table 2. Desired Smartphone App Functions Rated By Adults with Rheumatic and Musculoskeletal Disease (N=570). App Function n (% ) Participate in patient-centered research 299 (52.5) View my lab results 283 (49.7) Record my symptoms (e.g. pain, fatigue) or disease flares to track my health over time 278 (48.8) Record my symptoms and share how I am doing with my rheumatology provider to know if I am meeting my treatment goals 230 (40.4) Get educational information about my disease 225 (39.5) Keep track of the medications prescribed by doctor 200 (35.1) Schedule and keep track of my medical appointments, rheumatology and other 199 (34.9) Track the vaccines I get (i.e. vaccination record) 188 (33.0) Help me improve some of my health habits (e.g. sleep, diet, exercise) 187 (32.8) Keep track of my use of over-the-counter, complementary or alternative therapies (herbs, tinctures, acupuncture, massage, stretching, etc.) 174 (30.5) Get support for my disease from trained patients with my same health condition (i.e. ‘peer coaching’) 144 (25.3) Conclusion People with RMD prioritized information about medications and prognosis in educational materials, providing guidance for the development of educational tools. A sizeable minority felt educational materials were an important component of a smartphone app, but also identified other important features such as participation in research. Disclosure of Interests W. Benjamin Nowell Grant/research support from: Research support from AbbVie, Amgen, Eli Lilly and Scipher, Kelly Gavigan: None declared, Kimberly Garza: None declared, Alexis Ogdie: None declared, Michael George: None declared, Jessica A. Walsh Consultant of: AbbVie, Amgen, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Merck, and Pfizer, Maria Danila: None declared, Shilpa Venkatachalam: None declared, Laura Stradford: None declared, Jeffrey Curtis Consultant of: AbbVie, Amgen, BMS, Corrona, Eli Lilly and Company, Gilead, Janssen, Myriad, Novartis, Pfizer, Regeneron, Roche, and UCB, Grant/research support from: AbbVie, Amgen, BMS, Corrona, Eli Lilly and Company, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB

Upadacitinib (UPA) a été évalué pour le traitement de la SA chez des patients (pts) naïfs de bDMARDs [1] et des pts ayant eu une réponse inadéquate (IR ; définie comme une intolérance et/ou un manque d’efficacité) aux bDMARDs (bDMARD-IR) [2]. Cette analyse post hoc a évalué l’efficacité et la tolérance d’UPA dans des sous-groupes (ss-gpes) de pts bDMARD-IR ayant une SA en fonction du traitement (ttt) antérieur. Dans l’essai de phase 3 SELECT-AXIS 2 en cours, des pts SA, bDMARD-IR et remplissant les critères de NYm (n = 420) ont été randomisés selon un ratio 1:1 pour recevoir UPA 15 mg 1x/j (n = 211) ou un placebo (PBO, n = 209) pendant 14 semaines (S). Les critères d’éligibilité incluaient un manque d’efficacité après ≥ 12S de ttt par 1 bDMARD antérieur (TNFi ou IL-17i) et/ou une intolérance à 1 ou 2 bDMARDs antérieurs, quelle que soit la durée du ttt. Un manque d’efficacité de 2 bDMARDs n’était pas autorisé. Le critère principal était la réponse ASAS40 à S14. Cette analyse post hoc a évalué à S14 et en ss-gpes en fonction du ttt antérieur, la réponse ASAS40 et les critères suivants : ASDAS-CRP LDA (< 2,1) et amélioration par rapport à l’inclusion de la douleur rachidienne évaluée par le pt, du BASFI et du SPARCC-IRM rachis. Les analyses en ss-gpes ont été réalisées en fonction du nbre (1 ou 2), du mécanisme d’action (TNFi ou IL-17i), du manque d’efficacité (TNFi ou IL-17i) et de l’intolérance (oui ou non) des bDMARDs antérieurs. Les caractéristiques à l’inclusion étaient similaires dans les gpes UPA et PBO.(2) La majorité des pts avaient été traités antérieurement par 1 TNFi (UPA : 73 %, PBO : 76 %) ; 4 % et 5 % des pts UPA et PBO, respectivement, avaient reçu 1 TNFi et 1 IL-17i. Le taux de réponse ASAS40 était plus élevé avec UPA vs PBO (Delta : 22–33 %) à S14 pour tous les ss-gpes (Fig. 1). La réponse ASDAS-CRP LDA et l’amélioration vs l’inclusion du BASFI, de la douleur rachidienne et du SPARCC-IRM rachis étaient également plus élevées avec UPA vs PBO pour tous les ss-gpes (Delta : 28–37 % ;1,0–1,6 ; 1,3–2,3 et 0,8–4,8, respectivement) (Fig. 2). Le taux d’événements indésirables (EI) était plus élevé pour UPA vs PBO indépendamment de la tolérance des bDMARDs antérieurs. Néanmoins, le taux d’EI ayant entraîné l’arrêt du ttt était similaire pour les pts ayant eu ou non une intolérance à un bDMARD antérieur (0 % vs 1,5 % et 0 % vs 1,4 %, respectivement, pour UPA vs PBO) (Tableau 1). Les taux d’EI, EI graves (EIG) et infections graves étaient plus élevés chez les pts UPA ayant eu une intolérance à un bDMARD antérieur vs ceux sans intolérance (52 % vs 36 %, 5 % vs 2 %, 20 % vs 13 % et 5 % vs 1 %, respectivement). Aucun décès n’a été rapporté. Dans SELECT-AXIS 2, UPA a démontré une meilleure efficacité par rapport au PBO à S14 pour tous les ss-gpes de pts SA bDMARD-IR. Le profil de tolérance d’UPA était cohérent avec celui de l’étude, quelle que soit la tolérance des bDMARDs antérieurs. Bien que la possibilité de conclure soit limitée par la petite taille de certains ss-gpes, le rapport B/R d’UPA était généralement favorable chez les pts SA bDMARD-IR.

BackgroundAnkylosing spondylitis (AS) is a chronic, systemic inflammatory condition characterized by inflammatory back pain and is associated with extra-musculoskeletal manifestations and systemic comorbidities. Secukinumab (SEC) doses of 150 mg and 300 mg are approved to treat AS, although no dose escalation studies are available in patients who have inadequate response to SEC 150 mg.ObjectivesThe ASLeap study (NCT03350815) estimated the difference in clinical response to SEC 300 mg vs 150 mg at Week (Wk) 52 in patients with AS who failed to achieve Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease status on SEC 150 mg at Wk 16.MethodsIn this randomized, double-blind, parallel-group, multicenter, phase 4 study, 322 patients with AS were assigned to receive open-label SEC 150 mg administered per the label for 16 Wks (period 1). At Wk 16, patients who did not achieve inactive disease (ASDAS < 1.3) at Wks 12 and 16 were randomized 1:1 in a double-blind manner to SEC 150 mg or escalated to SEC 300 mg q4w to Wk 52 (period 2). The primary efficacy variable was achievement of ASDAS < 1.3 and the primary analysis time point was Wk 52. Secondary efficacy variables were achievement of ASDAS clinically important improvement ≥ 1.1, 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), Assessment of SpondyloArthritis international Society responses (ASAS20, ASAS40, and ASAS partial remission), and change from baseline in BASDAI, ASAS Health Index (ASAS-HI), and the Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-F). Safety was evaluated by incidence of treatment-emergent adverse events (TEAEs) through Wk 52. No statistical hypothesis tests for superiority or equivalence were planned in the protocol and none were performed.ResultsOf 279 patients receiving SEC 150 mg who completed the 16-wk open-label period 1, 22 (7.9%) achieved ASDAS < 1.3 at Wks 12 or 16 and continued receiving SEC 150 mg; 207 patients did not attain ASDAS < 1.3 at Wk 12 and Wk 16 and initiated period 2. Demographics and baseline disease characteristics were balanced between patients randomized to SEC 150 mg and SEC 300 mg, including the proportion of patients who were TNFi naive (SEC 150 mg: 73 [72.3%]; SEC 300 mg: 73 [69.5%]) (Table 1). Approximately 60% of patients in either SEC group were HLA-B27 positive. After having an inadequate response to SEC 150 mg through Wk 16, patients receiving either dose of SEC experienced similar improvements at Wk 52 in disease activity as measured by achievement of ASDAS < 1.3, ASDAS clinically important improvement ≥ 1.1, BASDAI50, ASAS20, ASAS40, and ASAS partial remission; and mean changes in BASDAI, quality of life as measured by ASAS HI, and fatigue as measured by FACIT-F (Figure 1). The incidence of TEAEs through Wk 52 was similar between patients receiving SEC 300 mg (63.4%) and 150 mg (68.6%).Table 1.Demographics and Baseline Disease Characteristics of Patients in Period 2 (safety set)CharacteristicSecukinumab 150 mg → 300 mg N = 101Secukinumab 150 mg → 150 mg N = 105Age, mean (SD), years48.5 (14.1)47.0 (13.7)Female, n (%)43 (42.6)52 (49.5)BMI, mean (SD), kg/m232.0 (8.0)32.1 (7.7)HLA-B27 positive, n (%)60 (59.4)65 (61.9)Time since axial symptom onset, mean (SD), years13.9 (11.7)14.0 (12.5)Time since diagnosis of AS, mean (SD), years4.7 (8.6)5.1 (9.7)TNFi naive, n (%)73 (72.3)73 (69.5)History of extra-axial involvement, n (%)Peripheral arthritis34 (33.7)30 (28.6)Enthesitis29 (28.7)31 (29.5)Uveitis13 (12.9)17 (16.2)Psoriasis14 (13.9)14 (13.3)Dactylitis7 (6.9)4 (3.8)Inflammatory bowel disease2 (2.0)1 (1.0)AS, ankylosing spondylitis; BMI, body mass index; TNFi, tumor necrosis factor inhibitor.ConclusionPatients with AS who did not achieve inactive disease by Wk 16 after receiving SEC 150 mg experienced similar clinical response and safety through Wk 52 regardless of dose escalation to SEC 300 mg or continuation on SEC 150 mg.AcknowledgementsThis study was funded by Novartis Pharmaceuticals Corporation. Medical writing support was provided by Richard Karpowicz, PhD, CMPP, of Health Interactions, Inc, and was funded by Novartis Pharmaceuticals Corporation. This abstract was developed in accordance with Good Publication Practice (GPP3) guidelines. Authors had full control of the content and made the final decision on all aspects of this publication.Disclosure of InterestsAtul Deodhar Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB, Alan Kivitz Shareholder of: Amgen, Gilead, GSK, Novartis, Pfizer, and Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, GSK, Eli Lilly, Horizon, Merck, Novartis, Pfizer, Sanofi, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Gilead, Janssen, Pfizer, Regeneron, Sanofi, and Sun Pharma, Marina Magrey Consultant of: Eli Lilly and Novartis, Grant/research support from: AbbVie, Amgen, and UCB, Jessica A. Walsh Consultant of: Amgen, Lilly, Novartis, and UCB, Grant/research support from: AbbVie and Pfizer, Philip J Mease Speakers bureau: AbbVie, Amgen, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, and UCB, Maria Greenwald Grant/research support from: AbbVie, Eli Lilly, Novartis, Pfizer, Galapagos, and Janssen, Renato Calheiros Employee of: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Farid Kianifard Employee of: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Chelsea Elam Employee of: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Kriti Nagar Employee of: Novartis Healthcare Pvt Ltd, Hyderabad, India, Adam Winseck Employee of: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Lianne S. Gensler Consultant of: Galapagos, Eli Lilly, Janssen, and Pfizer, Grant/research support from: UCB Pharma, AbbVie, Amgen, and Novartis.