The main treatment goal in axial spondyloarthritis (axSpA) is to maximize long-term quality of life, along with achieving symptom control and preservation of function and social participation.1 From the patients’ perspective, the most important aims of treatment are the reduction of pain and stiffness and the preservation of function and mobility, along with employment and participation in society.2 Since it may take several years for functional changes to occur as a result of new bone formation, reductions in disease activity and inflammation are the main targets in the first years of treatment.3
Since ankylosing spondylitis (AS), also known as radiographic axSpA, is a slowly-progressing disease without reliable biomarkers for assessing disease activity and response to biologic therapy, there is a real need for a comprehensive clinical assessment of AS patients in daily practice. A variety of patient-reported tools have been developed to assess the disease status of AS patients in clinical studies; however, there is a need for clinical assessments used to determine disease status in daily practice.4
- The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) remains the gold standard for assessing disease activity in routine practice; however, it has a poor correlation with C-reactive protein (CRP) levels and magnetic resonance imaging (MRI) inflammation.
- The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a validated and highly discriminatory tool for assessing disease activity in AS, but it may lack some feasibility because erythrocyte sedimentation rate (ESR) and CRP values are often not available during a clinic visit.
- The Routine Assessment of Patient Index Data 3 (RAPID-3) and Assessment of Spondyloarthritis International Society 40 (ASAS40) may be useful in assessing patients with AS quantitatively over time in busy clinical settings.
Assessing clinical outcomes: treating to target and finding the “window of opportunity”
Treat-to-target (T2T) is an established treatment paradigm in rheumatological conditions such as rheumatoid arthritis (RA) and is gaining traction in axSpA. This concept involves regular disease monitoring and a clear understanding of flares; ideally, it aims at tight control. Evidence in early RA supports the benefits of T2T in the prevention of damage, maintenance of physical function, reduction of comorbidity risks, and even improvement in work capacity.5 Treat-to-target has also been advocated for psoriatic arthritis (PsA), for which a validated definition of minimum disease activity is already established.1,5,6
In the case of axSpA, the T2T approach was originally based on evidence from other inflammatory conditions, which aim to direct therapy to a clear target such as disease remission or low disease activity, with the ultimate goal of maximizing quality of life in affected individuals.1 Set treatment targets have yet to be determined.
Another important consideration with T2T is when to intervene. While evidence is limited, available data suggest that therapy should be commenced at an early stage of the disease, particularly when the process of bone repair expected to occur after an inflammatory phase has not yet been initiated.1
The “window of opportunity” is another concept critical to RA treatment. Most notably, early treatment changes the outcome of RA treatment, resulting in response rates that are higher with earlier disease-modifying antirheumatic drug (DMARD) use, and damage that is substantially reduced.7 In axSpA, MRI studies and trials of early tumor necrosis factor (TNF) inhibitor therapy and withdrawal all suggest that early effective suppression of inflammation has the potential to reduce radiographic damage. This suggests that the concept of a window of opportunity is relevant not only to RA but also to axSpA. However, the challenge remains to identify high-risk patients early and to commence treatment without delay. Further research needs to focus on the evidence for early intervention and identification of high-risk individuals.7
Is sustained drug-free remission a possibility?
Unfortunately, sustained drug-free remission is unlikely to be achieved following treatment with TNF inhibitor therapy. Additionally, numerous studies have demonstrated the near inevitability of relapse upon discontinuation of treatment for AS patients.8 For example, in one study, 97.6% of patients had relapsed by 52 weeks after discontinuation of infliximab following 3 years of continuous treatment. This appears to be the case even when patients are in remission or have a normal CRP level at discontinuation.9 Even in early disease, relapse typically occurs after treatment discontinuation. In the Infliximab for Treatment of Axial Spondyloarthritis trial (INFAST), patients with axSpA of <3 years duration were treated with infliximab plus naproxen for 28 weeks, and those in clinical remission were then discontinued. By week 52, 52.5% of the patients in the active treatment group were no longer in remission.10 The ESTHER Trial investigated the frequency and duration of drug-free remission after one year of treatment with etanercept versus sulfasalazine in early axSpA. In this trial, after patients with axSpA were treated with etanercept for one year, those in clinical and imaging remission were then discontinued and followed for a further year. Only 8% were in drug-free remission at 2 years.8,11
- Marzo-Ortega H, Gaffney KM, Gaffney K. Defining the target: clinical aims in axial spondyloarthritis. Rheumatology (Oxford). 2018;57(suppl 6):vi18-vi22.
- 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;76:978-991.
- Braun J. Axial spondyloarthritis including ankylosing spondylitis. Rheumatology (Oxford). 2018;57(suppl 6):vi1-vi3.
- Magrey M, Ritchlin C. Measuring outcomes in ankylosing spondylitis: pearls and pitfalls. Curr Opin Rheumatol. 2019;31:109-117.
- Smolen JS. Treat-to-target as an approach in inflammatory arthritis. Curr Opin Rheumatol. 2016;28:297-302.
- Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis. 2010;69:48-53.
- Robinson PC, Brown MA. The window of opportunity: a relevant concept for axial spondyloarthritis. Arthritis Res Ther. 2014;16:109.
- Noureldin B, Barkham N. The current standard of care and the unmet needs for axial spondyloarthritis. Rheumatology (Oxford). 2018;57(suppl 6):vi10-vi17.
- Baraliakos X, Listing J, Brandt J, et al. Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab. Arthritis Res Ther. 2005;7:R439-R444.
- Sieper J, Lenaerts J, Wollenhaupt J, et al. Maintenance of biologic-free remission with naproxen or no treatment in patients with early, active axial spondyloarthritis: results from a 6-month, randomised, open-label follow-up study, INFAST part 2. Ann Rheum Dis. 2014;73:108-113.
- Song IH, Althoff CE, Haibel H, et al. Frequency and duration of drug-free remission after 1 year of treatment with etanercept versus sulfasalazine in early axial spondyloarthritis: 2 year data of the ESTHER trial. Ann Rheum Dis. 2012;71:1212-1215.