OP0108 RANDOMIZED CONTROLLED TRIAL OF ORAL CORTICOSTEROIDS IN AXIAL SPONDYLOARTHROPATHY: MODIFIED COBRA REGIME
Authors: D. Mishra, G. Naidu, V. Kumar, S. K. Sharma, A. Sharma, S. Jain, V. Dhir
Journal: Annals of the Rheumatic Diseases (2020)

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. Figure 1. Change in mean BASDAI Table 1. Changes in disease indices and inflammatory markers at 24 weeks Changes in Parameters (24 weeks-baseline) Placebo Corticosteroid P value ESR, Median (IQR) 0 (-11 to 21) -13 (-37 to 4) 0.01 CRP mg/L Median (IQR) 0 (-8.8 to 13) -9 (-22.7 to 0) 0.03 BASDAI (mean ± SD) - 0.51 ± 1.6 - 1.88 ± 2.5 0.03 BASMI (mean ± SD) -0.25 ± 0.8 -0.56 ± 0.9 0.23 BASFI (mean ± SD) -0.35 ± 2.3 -1.48 ± 3.1 0.28 BAS-G (mean ± SD) -1.02 ± 2.7 -1.86 ± 2.5 0.32 ASDAS-ESR (mean ± SD) -0.13 ± 1.0 -1.11 ± 1.1 0.001 ASDAS-CRP (mean ± SD) -0.24 ± 1.1 -1.17 ± 1.3 0.006 Figure 2. Clinically important and Major improvement at 24 weeks 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 &amp; 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