Comparative performance of composite measures from two phase III clinical trials of ixekizumab in psoriatic arthritis

Abstract

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.

Keywords: autoimmune diseases; patient reported outcome measures; psoriatic arthritis.

Conflict of interest statement

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.

© 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.

Figures

Figure 1

Proportion of patients treated with ixekizumab who achieved composite measure endpoints in SPIRIT-P1 (left panels) and SPIRIT-P2 (right panels) for MDA (A), VLDA (B), PASDAS LDA (C), PASDAS NR (D), GRACE LDA (E), DAPSA LDA (F), DAPSA Remission (G), mCPDAI LDA (H), mCPDA VLDA (I). *P

Figure 2

Venn diagrams representing the number of patients treated with biologics meeting different criteria for remission (A) or LDA (B) at week 24. DAPSA, Disease Activity index for Psoriatic Arthritis; GRACE, GRAppa Composite scorE; mCPDAI, modified Composite Psoriatic Disease Activity Index; MDA, minimal disease activity; N, number of patients in the analysis population; NR, near remission; PASDAS, Psoriatic Arthritis Disease Activity Score; VLDA, very low disease activity.

Figure 3

Residual disease activity by percentile for LDA achievers (left panels) and remission achievers (right panels) for patient pain VAS (A), patient global VAS (B), HAQ-DI (C), SF-36 PCS (D) and SF-36 MCS (E). DAPSA, Disease Activity index for Psoriatic Arthritis; GRACE, GRAppa Composite scorE; HAQ-DI, Health Assessment Questionnaire-Disability Index; LDA, low disease activity; mCPDAI, modified Composite Psoriatic Disease Activity Index; MCS, mental component summary; MDA, minimal disease activity; n, number of patients in the specified category; NR, near remission; PASDAS, Psoriatic Arthritis Disease Activity Score; PCS, physical component summary; Pt, patient; SF-36, 36-item short-form health survey; VAS, visual analogue scale; VLDA, very low disease activity.

Figure 4

Composite performance by baseline structural damage at week 24. LSM change from baseline and per cent mean change from baseline for mCPDAI (A), DAPSA (B), PASDAS (C) and GRACE (D) by baseline mTSS subgroup and proportion of patients achieving mCPDAI LDA/REM (E), DAPSA LDA/REM (F), PASDAS LDA/NR (G), GRACE LDA (H) and MDA/VLDA (I) by baseline mTSS subgroup. Horizontal dotted lines represent the cut-off points LDA and REM. Text within vertical arrows indicates per cent change from baseline values. *P

Figure 5

Composite performance by baseline functional disability based on HAQ-DI subgroup at week 24. (A–D) Mean score at baseline and LSM score at week 24 with per cent mean change from baseline (vertical arrows) for mCPDAI (A), DAPSA (B), PASDAS (C) and GRACE (D). (E–I) Proportion of patients achieving mCPDAI LDA/REM (E), DAPSA LDA/REM (F), PASDAS LDA/NR (G), GRACE LDA (H), and MDA/VLDA (I). Horizontal dotted lines in panels A–D represent the cut-off points LDA and REM. Text within vertical arrows indicates per cent change from baseline values. *P