OP0108 RANDOMIZED CONTROLLED TRIAL OF ORAL CORTICOSTEROIDS IN AXIAL SPONDYLOARTHROPATHY: MODIFIED COBRA REGIME. (2nd June 2020) - Mishra, D.
Abstract : Background: There is an unmet need of anti-inflammatory agents in AxSpA after NSAID failure. This is especially true for patients with persisting high disease activity and not having access to anti-TNFα. In this regard, corticosteroids may be helpful as a short-term measure. However, current guidelines recommend against oral corticosteroids citing insufficient evidence of efficacy. 1 . Also, there is an assumption that the dose required for benefit is much higher than RA, and thus untenable. It is unclear whether starting with a high dose followed by rapid taper would be effective (like the COBRA regime in RA) 2 . Objectives: To study the efficacy of the COBRA regime of oral corticosteroids in axial SpA over 24 weeks. Methods: This was a double blind placebo controlled randomized trial. Patients with active axial SpA (BASDAI ≥ 4) despite NSAIDs were randomized to either receive oral prednisolone or placebo as per COBRA regime, started on oral prednisolone at a dose of 60 mg, rapidly tapered weekly to reach a dose of 10 mg by 6 weeks and subsequently maintained on a low dose of 5 mg till 24 weeks. Primary end point was 50% improvement in BASDAI at week 24. Secondary end points were improvement in ASDAS and BASFI. Analysis was by intention-to-treat. Trial Registration# CTRI/2018/01/011342 Results: This study enrolled 65 patients (62 males) who were randomized to corticosteroid (n=32) or placebo (n=33) with mean ± SD age 28.5 ± 8.4 years and BASDAI 5.4 ± 1.0. Primary end point was reached in 12 (37.5%) and 3 (9%) patients treated with steroids and placebo respectively (p=0.007). On repeated measures analysis by general linear model, there was a significant difference between the two-groups in BASDAI (p= 0.03) (Figure-1). Patients in the corticosteroid group had significant improvement in BASDAI, ESR, CRP, ASDAS ESR and ASDAS CRP at 24 weeks (Table-1). Clinically important improvement in ASDAS CRP was achieved by significantly higher number of patients in steroid group (17 (55%) vs 6 (18%), p= 0.002). Major improvement in ASDAS ESR and ASDAS CRP was also higher in the steroid group (Figure-2). At 24 weeks, patients in the steroid group had significant reduction in IL-6 levels compared to that in placebo group (p= 0.007, data for 41 patients). Patients in the steroid group had more weight gain and facial puffiness, however no serious adverse events were noted in both the groups. Conclusion: Oral prednisolone given by COBRA regime was associated with significant improvement in disease activity scores in axial SpA at 24 weeks. This extends and supports results from a previous short term study. 3 Thus, corticosteroids may be an option for patients not having access to biologics, atleast for the short-term. References: [1]Ward M W, Deodhar A, Gensler L S et al 2019 Update of the American College of Rheumatology/ Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis & Rheumatology; 71:1599-1613(2019). [2]Landewé RB, Boers M, Verhoeven AC et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum.Feb;46(2):347-56 (2002). [3]H Haibel, C Fendler, J Listing et al. Efficacy of oral prednisolone in active ankylosing spondylitis: results of a double-blind, randomised, placebo-controlled short-term trial. Ann Rheum Dis;73:243–6 (2014). Disclosure of Interests: None declared