Barriers and facilitators to application of treat-to-target management in psoriatic arthritis and axial spondyloarthritis in practice: A systematic literature review.

OBJECTIVE: To review the evidence on barriers and facilitators to application of treat-to-target (T2T) in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) in daily practice. METHODS: A systematic search was conducted in MEDLINE/Embase up to December 2023, focusing on axSpA/PsA. Any type of quantitative/qualitative original research was eligible for inclusion if barriers or facilitators to application of T2T were explored. In a qualitative synthesis, barriers/facilitators were classified by the level to which they apply (healthcare provider [HCP], patient, organisation). RESULTS: Of 28 included studies, most focused on PsA (n = 21/28). Studies included patients (n = 23/28), HCP (n = 4/28) or both (n = 1/28). In total, over 25 barriers and 15 facilitators to application of T2T were identified. At the HCP level, most studies focused on the measurement of the target, especially in PsA, highlighting that agreement among instruments was suboptimal. At the patient level, the role of patient-reported outcomes (PROs), while deemed relevant, was shown to act as a barrier to achieve targets that included PRO components. At the organisational level, the increased time and resources needed for T2T were considered a barrier, although it was noted that T2T could also reduce healthcare use and sick leave. Notably, for several components, no facilitators were identified at all. CONCLUSION: Various barriers and facilitators were identified, acting on several levels. Data in axSpA were scarce, as was evidence on certain components of T2T. Future research should address these knowledge gaps and explore how these barriers and facilitators could be targeted to improve application of T2T in practice.

Efficacy and safety of biological DMARDs: a systematic literature review informing the 2022 update of the ASAS-EULAR recommendations for the management of axial spondyloarthritis.

OBJECTIVE: To update the evidence on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2022 update of the Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA. METHODS: Systematic literature review (2016-2021) on efficacy and safety of bDMARDs in axSpA (radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)). Eligible study designs included randomised controlled trials (RCTs), strategy trials and observational studies (the latter only for safety and extra-musculoskeletal manifestations). All relevant efficacy/safety outcomes were included. RESULTS: In total, 148 publications were included. Efficacy of golimumab and certolizumab was confirmed. Tumour necrosis factor inhibitor (TNFi) biosimilar-originator equivalence was demonstrated. RCT (n=15) data on efficacy of interleukin-17 inhibitors (IL-17i) demonstrated clinically relevant effects (risk ratio vs placebo to achieve ASAS40 response 1.3-15.3 (r-axSpA, n=9), 1.4-2.1 (nr-axSpA, n=2)). Efficacy of secukinumab/ixekizumab was demonstrated in TNFi-naïve and TNFi-inadequate responders. IL-23 and IL-12/23 inhibitors (risankizumab/ustekinumab) failed to show relevant benefits. Tapering of TNFi by spacing was non-inferior to standard-dose treatment. The first axSpA treat-to-target trial did not meet its primary endpoint, but showed improvements in secondary outcomes. No new risks were identified with TNFi use in observational studies (data lacking for IL-17i). Secukinumab (n=1) and etanercept (n=2) were associated with increased risk of uveitis in observational studies compared to monoclonal TNFi. CONCLUSIONS: New evidence supports the efficacy and safety of TNFi (originators/biosimilars) and IL-17i in r-axSpA and nr-axSpA, while IL-23i failed to show relevant effects. Observational studies are needed to confirm long-term IL-17i safety. PROSPERO REGISTRATION NUMBER: CRD42021257588.

ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update.

OBJECTIVES: To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA). METHODS: Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting. RESULTS: Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures. CONCLUSIONS: The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

Tapering or discontinuation of biological disease-modifying antirheumatic drugs in axial spondyloarthritis: A review of the literature and discussion on current practice.

Biological disease-modifying antirheumatic drugs (bDMARDs) have taken up an important role in the management of axial spondyloarthritis. Once stable remission or low disease activity has been achieved with bDMARDs, it may be possible to maintain this state with lower levels of these drugs. Studies consistently demonstrate that tapering of tumor necrosis factor alpha inhibitors (TNFi) is not inferior to full-dose continuation in terms of maintaining treatment response, while data for tapering of interleukin-17 inhibitors (IL-17i) is lacking. Complete discontinuation of TNFi and IL-17i, however, often results in relapse and should not be recommended at this moment. Clear safety benefits of tapering or discontinuation have not been shown, although studies were typically not designed to address this. Current evidence does not support specific tapering or discontinuation strategies, although stepwise disease activity-guided regimens do allow for a more personalized approach and might be preferred. The definition of what constitutes an appropriate disease state to initiate tapering or discontinuation is unclear, and requires further study. Also, reliable predictors of successful tapering and discontinuation have not yet been identified. Fortunately, if tapering or discontinuation fails, most patients are able to regain disease control when reverted to the original bDMARD regimen. Finally, most patients indicate that, when asked, they would be willing to try tapering if the rationale is clear and if it is in their best interests. The decision to taper or discontinue should be made through shared decision-making, as this could improve the likelihood of success.

Infliximab treatment reduces depressive symptoms in patients with ankylosing spondylitis: an ancillary study to a randomized controlled trial (ASSERT).

BACKGROUND: Patients with ankylosing spondylitis (AS) are at increased risk of depression. This increased risk has been hypothesized to be solely secondary due to AS-related symptoms, or additionally due to a common inflammatory pathway. From a clinical perspective, it is important to know whether treatment with tumor necrosis factor alpha inhibitors reduces depressive symptoms, while from a pathophysiological point of view, it would be insightful to understand whether such an effect would be a direct result of reduced inflammation, the result of reduced AS-related symptoms, or both. The objective of this study was to evaluate the effect of infliximab on depressive symptoms in patients with AS in a randomized-controlled trial setting. METHODS: Data were retrieved from a subgroup of patients from the AS Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT). Patients were randomly allocated to infliximab (n = 16) or placebo (n = 7) until week 24, after which all received infliximab until week 54. Associations between treatment group and depressive symptoms, measured with the Center for Epidemiological Studies Depression scale (CES-D, range 0-60 (best-worst)) at baseline and over time, were explored with generalized estimating equations (GEE). RESULTS: Mean CES-D score at baseline was 15.5 (SD 9.3) in the infliximab group and 17.3 (SD 5.7) in the placebo group. Twelve patients (52%) had a CES-D score > 16, suggestive for clinical depression. After 24 weeks, mean CES-D had decreased to 9.5 (SD 11.4) in the infliximab group, but was 18.0 (SD 6.9) in the placebo group. GEE revealed larger improvements in depressive symptoms (B = - 6.63, 95%CI - 13.35 to 0.09) and odds of possible depression (OR = 0.02, 95%CI 0.00 to 0.72) in the infliximab group, compared to the placebo group. Both associations largely disappeared when adjusted for self-reported disease activity and/or physical function. Additional adjustment for C-reactive protein (CRP) did not change results. CONCLUSIONS: Depressive symptoms are common in patients with AS and active disease. Infliximab improves these depressive symptoms in AS when compared to placebo by improving disease symptoms. We did not find an indication for a direct link between CRP-mediated inflammation and depressive symptoms. TRIAL REGISTRATION: Trial registration (ASSERT): NCT00207701 . Registered on September 21, 2005 (retrospectively registered).