OP0018 COMPARISON OF THE EFFECT OF TREATMENT WITH NSAIDs ADDED TO ANTI-TNF THERAPY VERSUS ANTI-TNF THERAPY ALONE ON PROGRESSION OF STRUCTURAL DAMAGE IN THE SPINE OVER TWO YEARS IN PATIENTS WITH ANKYLOSING SPONDYLITIS (CONSUL) – AN OPEN-LABEL, RANDOMIZED CONTROLLED, MULTICENTER TRIAL

Abstract

BackgroundThere is some evidence that NSAIDs, in particular celecoxib (CEL), might possess not only symptomatic efficacy but also disease-modifying properties in radiographic axial spondyloarthritis (r-axSpA) formerly known as ankylosing spondylitis, retarding progression of structural damage in the spine if taken continuously. For biological disease-modifying antirheumatic drugs (bDMARDs), retardation of structural damage progression has also been demonstrated, but at least 4 years of treatment seem to be necessary (at least for tumour necrosis factor inhibitors – TNFi) to see such an effect. Therefore, a combination of an NSAID with a TNFi might bring additional benefits in terms of retardation of structural damage progression especially in high-risk patients.ObjectivesThe aim of this RCT was to evaluate the impact of treatment with the COX-II-selective NSAID (CEL) when added to a TNFi (golimumab - GOL) compared with TNFi (GOL) alone on progression of structural damage in the spine over 2 years in patients with r-axSpA.MethodsEligible patients had r-axSpA and high disease activity (BASDAI ≥4), NSAID failure and risk factors for radiographic spinal progression: C-reactive protein >5 mg/l and/or ≥1 syndesmophyte(s). The trial consisted of two phases: a 12-week run-in phase, in which all included patients received treatment with GOL 50 mg every 4 weeks sc, followed by a 96-week controlled treatment period, in which patients who achieved a BASDAI improvement of ≥2 points were randomly assigned to GOL + CEL 200 mg bid or GOL alone arms. The primary endpoint was radiographic spinal progression as assessed by the change in the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) after 108 weeks in the intent-to-treat population, read by 3 independent readers blinded for the treatment arm and the time-point.ResultsOf the 157 screened patients, 81.5% (n=128) were enrolled into the run-in phase. 109 patients fulfilled the BASDAI response criterion at w12 and were randomized 1:1 (54 vs. 55) to GOL+CEL or GOL alone; 97 (45 vs. 52) patients completed the study at w108. Clinical characteristics of the randomized patients are shown in Tab. 1. The mSASSS change after w108 was 1.1 (95%CI 0.2; 2.0) vs. 1.7 (95%CI 0.8; 2.6) in the GOL+CEL vs. GOL alone groups, respectively, p=0.79. Figure 1 shows the cumulative probability of the mSASSS change in both treatment arms. New syndesmophytes in the opinion of three readers occurred in 11% vs. 25% of the patients in the GOL+CEL vs. GOL alone groups, respectively, p=0.12. During the study, a total of 14 serious adverse events (SAE) were reported (7 in the GOL+CEL group, 5 in the GOL alone group and 2 during the run-in phase).Figure 1.Cumulative probability plot of mSASSS progression over 108 weeks of treatment.ConclusionIn this study, a combined therapy with GOL+CEL did not show significant superiority over GOL monotherapy in retarding radiographic spinal progression over two years in r-axSpA patients.However, the observed numerical reduction in radiographic spinal progression associated with the combined treatment might be, however, clinically relevant for patients at high risk for progression.Table 1.Baseline characteristics of randomized patientsParametersGOL+CEL N=54GOL alone N=55All patients N=109validnvaluevalidnvaluevalidnvalueSex, malen (%)5440 (74.1)5541 (74.5)10981 (74.3)Age, yearsMean (SD)5439.9 (9.9)5537.5 (10.8)10938.7 (10.4)Smokern (%)5319 (35.8)5522 (40)10841 (38)HLA-B27 positivityn (%)5445 (83.3)5147 (92.2)10592 (87.6)BASDAIMean (SD)546.2 (1)556.1 (1.1)1096.1 (1.1)BASMIMean (SD)542.6 (1.9)542.9 (1.4)1082.8 (1.6)CRP > 5 mg/Ln (%)5438 (70.4)5538 (69.1)10976 (69.7)ASDAS-CRPMean (SD)543.6 (0.6)553.7 (0.9)1093.7 (0.8)Prior bDMARDsn (%)5417 (31.5)559 (16.4)10926 (23.9)Presence of ≥ 1 syndesmophyte(s)n (%)5427 (50)5528 (50.9)10955 (50.5)mSASSSMean (SD)5413.5 (16.9)5510.3 (13.2)10911.9 (15.2)AcknowledgementsThe CONSUL study has been supported by a grant from the German Ministry of Education and Research (BMBF), grant number FKZ 01KG1603 and study medication (golimumab) was provided free of charge by MSD Sharp & Dohme GmbH, Munich, Germany.Furthermore we would like to thank Anne Weber, Bianca Mandt, Claudia Lorenz, Hildrun Haibel, Judith Rademacher, Laura Spiller, Petra Tietz as well as all participating rheumatologist and included patients.Disclosure of InterestsFabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, UCB, Lilly, Burkhard Muche Speakers bureau: UCB Pharma, AMGEN, Consultant of: UCB Pharma, AMGEN, Valeria Rios Rodriguez Speakers bureau: AbbVie, Falk e.V., Murat Torgutalp: None declared, Mikhail Protopopov Consultant of: Novartis, Joachim Listing: None declared, Maryna Verba: None declared, Uta Kiltz: None declared, Jan Brandt-Juergens: None declared, Maren Sieburg: None declared, Swen Holger Jacki: None declared, Joachim Sieper Speakers bureau: AbbVie, Janssen, Merck, Novartis, Consultant of: Abbvie, Janssen, Lilly, Merck, Novartis, UCB, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, and Pfizer.