LBA0002 EARLY (3-MONTH) AND MAINTAINED (12-MONTH) COMPARATIVE EFFECTIVENESS OF 5 DIFFERENT CLASSES OF ADVANCED THERAPIES IN A LARGE MULTINATIONAL COHORT OF REAL-WORLD PSA PATIENTS
Authors: W. Tillett, R. Alten, E. Lubrano, K. J. Ng, M. Ngantcha, I. De La Torre, D. Kennedy, N. Gullick, D. Mcgonagle
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> While Randomized Controlled Trials (RCTs) are the gold standard for efficacy, there is limited comparative data available for advanced therapies in psoriatic arthritis (PsA). Real-world (RW) evidence facilitates the comparison of a greater number of drugs, complementing RCTs. The <b>P</b>so<b>r</b>iatic Arthritis <b>O</b>bservational <b>S</b>tudy of <b>P</b>ersistence of <b>T</b>reatment (PRO-SPIRIT) is a multinational, prospective study investigating the RW use of biological or targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in PsA. <h3>Objectives:</h3> The primary objective was to report persistence at 24 months among patients who initiated a new b/tsDMARD. Secondary endpoints included descriptive and comparative effectiveness and survival data at 3, 12, and 24 months, among other timepoints. The predefined interim analysis presented here aimed to report (1) the baseline characteristics and (2) the comparative effectiveness of PsA treatments at three (M3) and twelve (M12) months. <h3>Methods:</h3> Results from the completed 12-month visit (175 sites across six countries) were obtained by 11 December 2023. Descriptive (baseline characteristics) and baseline-adjusted comparative (RW effectiveness, using MMRM [Mixed Model for Repeated Measures]) analyses weighted by IPTW (Inverse Probability of Treatment Weighting) were powered for evaluating treatment groups above 10% of the total sample: ixekizumab (IXE), other interleukin (IL)-17A inhibitors (IL-17Ai; secukinumab [SECU] 150 mg or 300 mg), tumour necrosis factor inhibitors (TNFi), IL-12/23i, IL-23i, and Janus kinase inhibitors (JAKi). Missing data were imputed through simple and multiple imputation. <h3>Results:</h3> A total of 1192 patients were included in this study. Overall, baseline characteristics and disease activity were similar, except for patients on TNFi and SEC 150 mg having notably shorter disease duration and less previous b/tsDMARD experience, and higher proportions of the TNFi (53.5%) and JAKi (46.8%) patients concomitantly using conventional synthetic (cs)DMARDs at baseline; additionally, a smaller proportion of the JAKi patients presented with affected body surface area (BSA) ≥3% at baseline (25.8%; see Table 1), likely reflective of a channelling bias. Descriptive effectiveness is shown in Table 1. Comparative effectiveness analyses further confirmed that: (a) for the joints, IXE was as effective as TNFi and JAKi at both M3 and M12 in the improvement of clinical Disease Activity in PsA (cDAPSA) scores as well as tender (TJC) and swollen joint counts (SJC). Higher concomitant use of csDMARDs at baseline plus improvements in TJC (M12; Table 1) might have contributed to the pattern of cDAPSA scores seen with JAKi (Figure 1); interestingly, cDAPSA improvement was less prominent when comparing M12 TNFi and JAKi against the whole IL-17Ai class. At M3, both IXE and the IL-17Ai class were significantly better at improving cDAPSA, TJC, and SJC than IL-12/23i and IL-23i treatments (pooled due to low individual sample size), indicating faster response to IXE and IL-17Ai treatment; (b) in the skin, IXE showed significantly greater improvement in BSA (least squares mean difference) than TNFi at both M3 (IXE: -4.1 [-4.8 – -3.4]; TNFi: -2.6 [-3.3 – -2.0]) and M12 (-4.4 [-4.9 – -3.8]; -3.5 [-4.0 – -3.0]). As a large amount of data were missing for some of the seven components of Minimal Disease Activity (MDA), in addition to the apparent channelling bias rooted in baseline BSA, ad hoc analyses will be necessary to interpret and report the attainment of MDA. <h3>Conclusion:</h3> PRO-SPIRIT captures a heterogeneous sample of patients across six countries and five classes of advanced therapies and confirms that IXE is as effective as TNFi and JAKi at improving joint disease activity in PsA patients, despite the IXE subpopulation having greater b/tsDMARD experience and longer disease duration than those receiving a TNFi as well as fewer patients on concomitant csDMARDs than both the TNFi and JAKi groups. The study also demonstrates that IXE and the IL-17Ai class provide faster improvement in cDAPSA scores than either an IL-12/23i or IL-23i, and a clearly greater benefit in BSA than a TNFi. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Eli Lilly and Company would like to thank the participants, their caregivers, and the investigators, without whom this work would not be possible. The authors would also like to thank Jens Gammeltoft Gerwien, Walid Fakhouri, and Meadhbh O'Neill, for providing medical and statistical review, respectively. <h3>Disclosure of Interests:</h3> William Tillett AbbVie, Eli Lilly and Company, GSK, Janssen, Novartis, Ono-Pharma, Pfizer, UCB. AbbVie, Eli Lilly and Company, GSK, Janssen, Novartis, Ono-Pharma, Pfizer, UCB. Eli Lilly and Company, Janssen, Pfizer, UCB. Rieke Alten AbbVie, Amgen, BMS, Celltrion, Chugai, Eli Lilly and Company, Galapagos, Gilead, Janssen, Mylan/Viatris, Novartis, Pfizer, Roche, UCB. AbbVie, Amgen, BMS, Celltrion, Chugai, Eli Lilly and Company, Galapagos, Gilead, Janssen, Mylan/Viatris, Novartis, Pfizer, Roche, UCB. Ennio Lubrano AbbVie, Eli Lilly and Company, Janssen, Novartis, UCB. Khai Jing Ng Eli Lilly and Company, Eli Lilly and Company, Marcus Ngantcha Eli Lilly and Company, Eli Lilly and Company, Inmaculada De La Torre Eli Lilly and Company, Eli Lilly and Company, Dominika Kennedy Eli Lilly and Company, Eli Lilly and Company, Nicola Gullick AbbVie, Eli Lilly and Company, Janssen, Novartis, UCB. AbbVie, AbbVie, Astra Zeneca, Eli Lilly and Company, Galapagos, Janssen, Novartis. Dennis McGonagle AbbVie, Almiral, Bristol-Myers Squibb, Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB. AbbVie, AbbVie, Jannssen, Pfizer, UCB.