OP0315 WHICH RESPONSE OR STATUS CRITERION DISCRIMINATES BEST IN AXSPA?
Authors: A. Ortolan, S. Ramiro, A. Sepriano, R. B. M. Landewé, D. Van der Heijde, V. Navarro-Compán
Journal: Annals of the Rheumatic Diseases (2020)

Background: Response criteria and disease activity status used to assess treatment efficacy in axial spondyloarthritis (axSpA) are: the ASAS response criteria (ASAS20; 40; 5/6 and partial remission - PR), BASDAI50 and ASDAS-based criteria (clinically important/major improvement –CII/MI; low disease activity/inactive disease –LDA/ID). These outcomes are variably used in RCTs testing biological (b) and targeted-synthetic (ts)DMARDs. However, it remains unknown which are the most discriminative. Objectives: To compare the ability of different criteria to discriminate between the response to active treatment and placebo in axSpA. Methods: A systematic literature review was performed in Medline and Embase to identify RCTs of b- and tsDMARDs. Placebo-controlled RCTs meeting the primary endpoint were included provided they reported ≥2 response/status criteria. Outcomes were collected at the timepoint of primary endpoint assessment (PEA). Risk of bias was evaluated by The Cochrane tool. Meta-analysis with the Mantel-Haenszel method was conducted to calculate the Chi-square ( Χ 2 ) between percentages of patients fulfilling each criterion in the treatment arm versus the placebo arm (higher Χ 2 , better discrimination). Comparisons among criteria were conducted evaluating their performances across RCTs reporting the exact same outcomes at the PEA. Different sets of RCTs were used for the comparisons depending on the available outcomes (Table). Results: 29 RCTs fulfilled inclusion criteria. In total, 23/29 RCTs with PEA at 12, 14 or 16 weeks, all at a low risk of bias, could be considered for meta-analysis. Other 6 RCTs had later (e.g 24 weeks) or earlier (e.g. 6 weeks) PEA. Out of the 23 RCTs, only 16 reported at least a minimum set of ASAS20,-40, -PR and BASDAI50 (Table, Set 1): discriminative performances for ASAS40 were &gt;ASAS20&gt;BASDAI50&gt;ASAS-PR. In 11/16 RCTs ASAS5/6 was also included (Table, Set 2): this criterion showed the best performances among ASAS-based response criteria. 8/16 RCTs additionally included some ASDAS-based criteria (Table, Set 3): ASDAS-CII and -MI showed a much higher discrimination compared to the ASAS-based criteria. In only 3 trials could all criteria be compared, with the ASDAS-CII and -MI appearing as the most discriminative criteria, followed by ASAS 5/6 (Table, Set 4). Conclusion: Response criteria are more discriminative than status criteria. ASDAS-CII and ASDAS-MI showed the best discrimination between treatment/placebo arms. Using the ASDAS-CII as primary outcome in future RCTs can reduce the number of patients needed to be included while keeping the same statistical power. Table. Discriminative performances of response and status criteria in RCTs of biological and targeted synthetic DMARDs in axial spondyloarthritis Minimum set of outcomes Set 1: ASAS20,-40,-PR, BASDAI50 Set 2: ASAS20,-40,-5/6, -PR BASDAI50 Set 3: ASAS20,-40, -5/6, -PR BASDAI50 ASDAS-CII, -MI, -ID Set 4: All N° of RCTs Total=16* 16 11 8 3 Descending Χ 2 order Χ 2 Χ 2 Χ 2 Χ 2 1 ASAS40 339 ASAS5/6 334 ASDAS-CII 309 ASDAS-CII 124 2 ASAS20 316 ASAS40 266 ASDAS-MI 253 ASDAS-MI 65 3 BASDAI50 297 ASAS20 254 ASAS40 169 ASAS5/6 48 4 ASAS-PR 146 BASDAI50 248 BASDAI50 163 BASDAI50 39 5 - ASAS-PR 119 ASDAS-ID 117 ASAS40 34 6 - - ASAS20 98 ASDAS-LDA 27 7 - - ASAS-PR 80 ASAS-PR 22 8 - - - ASAS20 21 9 - - - ASDAS-ID 7 Legend. *total of 16 RCTs analysed, with different sets of RCTs within the 16 analysed based on the availability of response criteria; Χ 2= Chi-square; RCTs=randomized controlled trials; BASDAI= Bath Ankylosing Spondylitis Disease Activity Index; ASAS= Assessment in SpondyloArthritis International Society; PR= partial remission; CII= clinically important improvement; MI= major improvement; LDA= low disease activity; ID= inactive disease Disclosure of Interests: Augusta Ortolan: None declared, Sofia Ramiro: None declared, Alexandre Sepriano: None declared, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly &amp; Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB