PMID- 36171019 OWN - NLM STAT- MEDLINE DCOM- 20220930 LR - 20221114 IS - 2056-5933 (Electronic) IS - 2056-5933 (Linking) VI - 8 IP - 2 DP - 2022 Sep TI - Comparative performance of composite measures from two phase III clinical trials of ixekizumab in psoriatic arthritis. LID - 10.1136/rmdopen-2022-002457 [doi] LID - e002457 AB - BACKGROUND/OBJECTIVE: The aim of this study was to evaluate relative performance of composite measures in psoriatic arthritis and assess the impact of structural damage and functional disability on outcomes during ixekizumab treatment. METHODS: Data from SPIRIT-P1 and SPIRIT-P2 were analysed to evaluate the effect of ixekizumab on achievement of low disease activity (LDA) and remission with the minimal disease activity (MDA) and very low disease activity (VLDA) composite, Disease Activity index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score, GRAppa Composite ScorE and modified Composite Psoriatic Disease Activity Index (mCPDAI). Performance was compared by quantifying residual symptom burden and the impact of structural damage and functional disability. RESULTS: Significantly more ixekizumab-treated patients achieved treatment targets at week 24 versus placebo assessed with all composites. More patients achieved targets assessed by mCPDAI and DAPSA than other composites. Residual disease activity was similar between composites, but residual high patient-reported outcomes (PROs) and functional disability were more frequent when assessed with mCPDAI and DAPSA. Achievement of treatment targets was reduced by high baseline levels of structural damage and functional disability. CONCLUSION: Residual disease activity was similar in patients achieving treatment targets assessed with all composites, but residual high PROs and functional disability were more common when assessed with mCPDAI and DAPSA, most likely due to the absence/attenuated functional assessment in these composites. High baseline levels of structural damage and functional disability attenuated response rates with all composites, affecting MDA/VLDA most prominently; LDA may be the most appropriate target in these patients. TRIAL REGISTRATION NUMBER: NCT01695239. CI - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Coates, Laura C AU - Coates LC AUID- ORCID: 0000-0002-4756-663X AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK laura.coates@ndorms.ox.ac.uk. FAU - Smolen, Josef S AU - Smolen JS AD - Medical University of Vienna, Vienna, Austria. FAU - Mease, Philip J AU - Mease PJ AUID- ORCID: 0000-0002-6620-0457 AD - Department of Rheumatology, Swedish Medical Center, Providence St Joseph Health, and School of Medicine, University of Washington, Seattle, Washington, USA. FAU - Husni, M Elaine AU - Husni ME AD - Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Merola, Joseph F AU - Merola JF AD - Division of Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Lespessailles, Eric AU - Lespessailles E AD - University of Orleans, Orleans Hospital, Orleans, France. FAU - Kishimoto, Mitsumasa AU - Kishimoto M AUID- ORCID: 0000-0002-4007-1589 AD - School of Medicine, Kyorin University, Tokyo, Japan. FAU - Macpherson, Lisa AU - Macpherson L AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Bradley, Andrew J AU - Bradley AJ AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Bolce, Rebecca AU - Bolce R AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Helliwell, Philip S AU - Helliwell PS AUID- ORCID: 0000-0002-4155-9105 AD - School of Medicine, University of Leeds, Leeds, UK. LA - eng SI - ClinicalTrials.gov/NCT01695239 PT - Clinical Trial, Phase III PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - RMD Open JT - RMD open JID - 101662038 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antirheumatic Agents) RN - BTY153760O (ixekizumab) SB - IM MH - Antibodies, Monoclonal, Humanized MH - *Antirheumatic Agents/therapeutic use MH - *Arthritis, Psoriatic/diagnosis/drug therapy MH - Disease Progression MH - Humans MH - Severity of Illness Index MH - Treatment Outcome PMC - PMC9528721 OTO - NOTNLM OT - autoimmune diseases OT - patient reported outcome measures OT - psoriatic arthritis COIS- Competing interests: LCC is an associate editor for RMD Open and has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB; worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB; and has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB. JSS is on the editorial board at RMD Open and has received grant/research support for his institution from AbbVie, AstraZeneca, Eli Lilly and Company, Novartis, Pfizer, and Roche; consultancy fees from AbbVie, Amgen, AstraZeneca, Astro, BMS, Celgene, Celltrion, Chugai, Eli Lilly and Company, Gilead, ILTOO, Janssen, MSD, Novartis, Pfizer, Roche, R-Pharma, Samsung, Sanofi and UCB. PJM has received research grants, consulting fees and/or speaker fees from AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma. EH has consulted for AbbVie, Bristol-Myers Squibb, Pfizer, UCB, Novartis, Eli Lilly, Janssen and Genentech. JM is a consultant and/or investigator for Amgen, Bristol-Myers Squibb, Abbvie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma. EL has received speaker and consultant fees from Abbvie, Amgen, Janssen, Galapagos, Lilly, MSD and Novartis. MK has received advisory board fees and lecture fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, Kyowa Hakko Kirin, Mitsubishi Tanabe Pharma, Novartis Pharma, Ono, Pfizer and UCB; and lecture fees from Asahi Kasei Medical, Astellas Pharma, Ayumi Pharma, Boehringer Ingelheim, Celltrion Healthcare, Chugai Pharmaceutical, Daiichi Sankyo, Eisai and Teijin Pharma. LM and RB are employees and stockholders of Eli Lilly and Company. AJB was an employee at Eli Lilly and Company at the time of this this study and is a stockholder. PH received consulting fees from Eli Lilly and fees for educational services from Abbvie, Amgen, Novartis and Janssen. EDAT- 2022/09/29 06:00 MHDA- 2022/10/01 06:00 PMCR- 2022/09/28 CRDT- 2022/09/28 21:02 PHST- 2022/05/06 00:00 [received] PHST- 2022/08/29 00:00 [accepted] PHST- 2022/09/28 21:02 [entrez] PHST- 2022/09/29 06:00 [pubmed] PHST- 2022/10/01 06:00 [medline] PHST- 2022/09/28 00:00 [pmc-release] AID - rmdopen-2022-002457 [pii] AID - 10.1136/rmdopen-2022-002457 [doi] PST - ppublish SO - RMD Open. 2022 Sep;8(2):e002457. doi: 10.1136/rmdopen-2022-002457.