Rita Machado, MD, on bDMARDS and axSpA Remission

A team of researchers sought to determine whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) showed efficacy among patients with axial spondyloarthritis (axSpA) in achieving Assessment of Spondyloarthritis International Society partial remission (ASAS-PR) and/or Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID). 

Lead author Ana Rita Cruz-Machado, MD, from the Rheumatology Department of the Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon Academic Medical Centre in Lisbon, Portugal, answered some questions about the study and her team’s results and conclusions.

RHEUMATOLOGY CONSULTANT: Your research focused on assessing the efficacy of bDMARDs in achieving partial remission or inactive disease in patients with axSpA. What led you and your colleagues to select this topic for your research?

RITA MACHADO: The treat-to-target concept has been employed with several rheumatic diseases over the last years, and axSpA is no exception. According to the latest guidelines, remission or inactive disease represents the ultimate goal of treatment, considering that radiographic progression is more strongly inhibited in states of remission^(2,3,4). However, remission-like outcomes such as ASAS-PR and ASDAS-ID are poorly addressed in clinical trials in opposition to response outcomes. By this work, we intended to increase awareness on this issue and to evaluate the efficacy of bDMARDs in reaching remission outcomes through a systematic literature review of published randomized controlled trials (RCTs). 

RHEUM CON: Can you give us a brief summary of what your research team discovered in terms of the efficacy of bDMARDs in axSpA?

RM: By performing a systematic literature review and meta-analysis concerning RCTs that address ASAS-PR, we were able to conclude that bDMARDs have a clear impact in reaching this remission-like outcome vs placebo [RR  3.864 (95% CI 2.937, 5.085)].

RHEUM CON: You used the ASAS-PR and/or ASDAS-ID as “remission-like surrogates” to measure the efficacy of these therapeutic agents. Would you explain what you mean by “remission-like surrogates”? 

RM: In axSpA, there is no consensus definition of remission. Nevertheless, the ASAS-PR and ASDAS-ID scores have gained wide acceptance as clinical remission-like definitions in current practice^(5,6,7), for this reason we chose to use them as surrogates for the state of absent/minimal disease activity. 

RHEUM CON: In your conclusion, you noted the need for improved reporting of such surrogates. Can you give us more detail on why this need exists and what you think would make such improvements possible?

RM: In axSpA, structural damage is the primary consequence of the disease, causing pain, stiffness, and poor quality of life. We now have enough evidence supporting that radiographic progression is more strongly inhibited in states of remission^(2,3,8). Nevertheless, after a careful systematic literature review, only 42 trials addressing ASAS-PR or ASDAS-ID were retrieved. It is then clinically relevant that RCTs also choose to address these surrogates, together with the more often reported response criteria (such as ASAS 20/40, BASDAI, and ASDAS response criteria). 

References:

1. Machado AR, Rodrigues-Manica S, Silva JL, et al. Effect of biologic disease-modifying anti-rheumatic drugs targeting remission in axial spondyloarthritis: systematic review and meta-analysis. Rheumatology (Oxford). Published online July 22, 2020. doi:10.1093/rheumatology/keaa268
2. van der Heijde D, Ramiro S, Landewé R, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017; 76(6):978–991.doi:10.1136/annrheumdis-2016-210770
3. Smolen JS, Schöls M, Braun J, et al. Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Ann Rheum Dis. 2018; 77(1):3–17. doi: 10.1136/annrheumdis-2017-211734
4. Ward MM, Deodhar A, Gensler LS, 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 Rheumatol. 2019; 71(10):1599–1613. doi:10.1002/art.41042
5. Sieper J. How to define remission in ankylosing spondylitis? Ann Rheum Dis. 2012; 71:i93–i95. doi:10.1136/annrheumdis-2011-200798
6. Braun J, Sieper J. Remission and possible discontinuation of biological therapy in axial spondyloarthritis. Clin Exp Rheumatol. 2013;31(4 Suppl 78):S33–6. https://www.clinexprheumatol.org/abstract.asp?a=7492
7. Poddubnyy D, Gensler LS. Spontaneous, drug-induced, and drug-free remission in peripheral and axial spondyloarthritis. Best Pract Res Clin Rheumatol. 2014; 28(5):807–818. doi:10.1016/j.berh.2014.10.00
8. Landewe R, Dougados M, Mielants H, van der Tempel H, van der Heijde D. Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine. Ann Rheum Dis. 2009:68(6):863–867. doi:10.1136/ard.2008.091793