EULAR 2021—Rheumatologists and patients can reasonably ask: Is there a way to achieve sustained clinical remission in spondyloarthritis (SpA)? After all, a major goal of rheumatologic care is to return patients to the approximate levels of function and symptom-free existence they had prior to disease onset.
At EULAR 2021, Filip Van den Bosch, MD, head of clinic and associate professor of rheumatology in the Department of Rheumatology at Ghent University Hospital, Belgium, spoke on the topic of disease inactivity in patients with SpA. In the process, he imparted many clinical pearls regarding how to care for these patients.
Dr. Van den Bosch posed an interesting question at the start of the lecture: How does one define remission in a heterogeneous disease, such as SpA? One potential answer: Clinical remission or inactive disease is the absence of clinical and laboratory evidence of significant inflammatory disease activity. When looking at clinical trials, this definition would mean using the most stringent measures of disease inactivity as measured by outcomes scores, such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Ankylosing Spondylitis Disease Activity Score (ASDAS) and the Disease Activity in PSoriatic Arthritis score (DAPSA).
However, in SpA, clinical evaluation of disease goes beyond just looking at axial and peripheral arthritis. Rheumatologists must also take into account such domains as enthesitis, dactylitis, psoriasis, inflammatory bowel disease and uveitis.
Treatment
Over the past 20 years, dermatologists have succeeded in frequently achieving complete remission of skin psoriasis in patients treated with biologics, such as those targeting the interleukin (IL) 12, IL-17 and IL-23 pathways, said Dr. Van den Bosch. However, in rheumatology, advances in biologic treatments have not shown the same degree of near complete success. This result may, in part, reflect the fact that the resolution of skin disease is a clear and consistent outcome that can be measured across patients. But evaluating disease activity in a multi-dimensional disease, such as SpA, is more challenging.
Part of the challenge may be the characteristics of patients enrolled in clinical trials and how these traits have changed over time. Vandendorpe et al. examined patient characteristics in 12 phase 2 and phase 3 trials conducted on the subject of psoriatic arthritis (PsA) in the era of biologic therapy. This study found several objective measures, such as average swollen and tender joint count and C-reactive protein levels, have decreased in study patient populations in recent years, whereas more subjective measures, such as patient assessment of pain and disease activity and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, have increased over time.1 Such changes in study populations may make it challenging to compare outcomes of patients in the present day to those of patients evaluated in studies 10 or 20 years ago.
Patient Care
Dr. Van den Bosch outlined several steps of his approach to caring for patients with SpA.
Strategy #1: His first approach centers on correctly using older drugs, including appropriately dosed non-steroidal anti-inflammatory drugs (NSAIDs), for SpA. In a study by van der Heijde et al., 387 patients with ankylosing spondylitis were randomized to receive one of two doses of etoricoxib (a cyclooxygenase 2 selective inhibitor) vs. 1,000 mg of naproxen daily vs. placebo. Over the initial six weeks of study, researchers found the patients receiving either etoricoxib or naproxen achieved statistically significant improvements in all co-primary end points: patient assessment of spine pain, patient global assessment of disease activity and the Bath Ankylosing Spondylitis Functional Index.2
Dr. Van den Bosch also presented data indicating rates of partial remission in axial SpA, per the Assessment in SpondyloArthritis International Society (ASAS), with the use of naproxen are similar to the rates of minimal disease activity in PsA with the use of methotrexate. However, it should be noted that it’s challenging to compare different outcome measures in different diseases. Nevertheless, NSAIDs retain an important role in controlling disease activity for many patients, and rheumatologists would be wise to not neglect these therapies.
Strategy #2: Dr. Van den Bosch’s next approach is based on the concept of using newer, more advanced medications to care for patients. Good data exists that minimal disease activity can be reached in such conditions as PsA with several modalities of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). Perhaps more challenging is knowing how to compare some of these medications in a head-to-head fashion.
Mease et al. compared the efficacy and safety of ixekizumab, an IL-17 inhibitor, with adalimumab, a tumor necrosis factor (TNF) α inhibitor, for the treatment of patients with PsA for whom conventional synthetic DMARD therapy proved inadequate. The authors found ixekizumab was superior to adalimumab in achieving simultaneous improvement of joint and skin disease, as measured by ACR50 criteria, and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI-100).3 More head-to-head trials would be helpful in allowing clinicians to select one biologic or targeted synthetic DMARD over another in an effort to find the right therapy for each patient.
Strategy #3: This approach revolves around treat-to-target and tight disease control parameters. Dr. Van den Bosch pointed to the TICOPA trial, which sought to use an early intervention, treat-to-target approach for the care of patients with PsA. In this study, Coates et al. demonstrated tight control of PsA disease activity significantly improved joint and skin outcomes for patients with newly diagnosed disease. No unexpected severe adverse events were noted.4
The results from a similarly designed trial in ankylosing spondylitis were more complex. In comparing a tight-control/treat-to-target strategy in axial SpA with usual care, Molto et al. did not find a statistically significant difference between treatment groups using the primary endpoint of the percentage of patients with a greater than 30% improvement on the ASAS-Health Index (ASAS-HI). However, the authors wrote that the tight-control/treat-to-target group did achieve more favorable secondary efficacy outcomes, had a similar safety profile and was more cost effective at one year than the group receiving usual care.5 These findings may indicate a role for treat-to-target and tight control approaches in ankylosing spondylitis management.
Dr. Van den Bosch ended his talk with the concept of the DEER approach, which stands for dedicated, empathic and educated rheumatologist. This approach means rheumatologists should keep in mind such issues as mental health, socioeconomic factors, central pain sensitization syndromes, such as fibromyalgia, and comorbidities that may affect a patient’s likelihood to respond or not respond to treatment.
Jason Liebowitz, MD, completed his fellowship in rheumatology at Johns Hopkins University, Baltimore, where he also earned his medical degree. He is currently in practice with Skylands Medical Group, N.J.
References
- Vandendorpe AS, de Vlam K, Lories R. Evolution of psoriatic arthritis study patient population characteristics in the era of biological treatments. RMD Open. 2019 Jan 22;5(1):e000779. eCollection 2019.
- van der Heijde D, Baraf HS, Ramos-Remus C, et al. Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: Results of a fifty-two-week, randomized, controlled study. Arthritis Rheum. 2005 Apr;52(4):1205–1215.
- Mease PJ, Smolen JS, Behrens F, et al. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naive patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. Ann Rheum Dis. 2020 Jan;79(1):123–131.
- Coates LC, Moverley AR, McParland L, et al. Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): A U.K. multi-centre, open-label, randomised controlled trial. Lancet. 2015 Dec 19;386(10012):2489–2498.
- Molto A, López-Medina C, Van den Bosch FE, et al. Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: Results of the open-label, pragmatic, cluster-randomised TICOSPA trial. Ann Rheum Dis. 2021 May 6:annrheumdis-2020-219585. Epub ahead of print.