Impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and adverse events of special interest in patients with rheumatoid arthritis or spondyloarthritis: a systematic analysis of the literature and meta-analysis

Vinson, Dorothee; Molet-Benhamou, L.; Degboé, Yannick; Broeder, A. Den; Ibrahim, Fatma A. A.; Pontes, Caridad; Westhovens, René; Závada, Jakub; Pham, Thao; Barnetche, Thomas; Constantin, Arnaud; Ruyssen‐Witrand, Adeline

doi:10.1186/s13075-020-02188-x

Cited by 26 publications

(6 citation statements)

References 45 publications

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“…The de-escalation of the biological disease-modifying anti-rheumatic drug (predominantly anti-TNF-α agents) the or the JAK inhibitor was not different from continuation of the initial regimen with respect to the incidence of serious infections (risk difference 0.01, 95% CI −0.00-0.02, p = 0.13, I 2 = 0%). In contrast to our systematic review, Vinson et al did not study dermatological adverse effects or non-serious infections [50].…”

Section: Discussioncontrasting

confidence: 66%

De-Escalation of Anti-Tumor Necrosis Factor Alpha Agents and Reduction in Adverse Effects: A Systematic Review

2022

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Background: The long-term use of anti-TNF-α agents can lead to adverse effects, such as infections and immune-mediated cutaneous reactions. Whether de-escalation by dose reduction or interval lengthening reduces these adverse effects is uncertain. This systematic review aims to compare the incidence of infections and skin manifestations after anti-TNF-α dose de-escalation with standard dosing. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception to January 14, 2022. Randomized controlled trials (RCTs) and observational studies comparing anti-TNF-α de-escalation strategies with standard dosing among patients with inflammatory conditions, that report on infections, skin manifestations, or both, were included. The risk of bias was assessed with the revised Cochrane risk-of bias tool (RCTs) or the Newcastle–Ottawa scale (non-RCTs). Results: Fourteen RCTs and six observational studies (or 2706 patients) were included. Eight RCTs had low risk of bias or some concerns. Four non-RCTs were of good methodological quality. The studies described patients with axial spondyloarthritis (8 studies, 780 patients), rheumatoid arthritis (7 studies, 1458 patients), psoriasis (3 studies, 332 patients), or inflammatory bowel disease (2 studies, 136 patients). De-escalation strategies included interval lengthening (12 studies, 1317 patients), dose reduction (6 studies, 1130 patients), or both (2 studies, 259 patients). Overall, the occurrence of infections and skin manifestations did not differ between standard treatment and de-escalation. The disappearance of infections or skin manifestations after de-escalation was only reported in two studies. The majority of studies focused on etanercept and adalimumab. Heterogeneity in reporting of infections and skin manifestations precluded meta-analysis. Conclusion: We found that anti-TNF-α de-escalation does not reduce infections or skin reactions. A de-escalation strategy should not be recommended for the sole purpose of reducing drug-related adverse effects. The meticulous documentation of adverse effects is recommended to further address this question. Registration: PROSPERO CRD42021252977.

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Section: Discussioncontrasting

confidence: 66%

De-Escalation of Anti-Tumor Necrosis Factor Alpha Agents and Reduction in Adverse Effects: A Systematic Review

2022

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“…There is a population of so-called ‘treatment refractory’ or ‘difficult to treat’ patients with RA304 305 that have failed to respond to at least two biological disease-modifying antirheumatic drugs (bDMARDs) of different mechanisms of action 306. In addition, even among those patients who achieve clinical remission, many quickly relapse following the withdrawal of treatment 307–310. A recent study311 has looked into the real-world evidence using data from a registry of people living with inflammatory joint diseases (RA, ankylosing spondylitis or psoriatic arthritis) and treated with bDMARDs.…”

Section: Implications For Treatmentmentioning

confidence: 99%

Inflammatory tissue priming: novel insights and therapeutic opportunities for inflammatory rheumatic diseases

Hoffmann,

Kirchner,

Krönke

et al. 2024

Ann Rheum Dis

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Due to optimised treatment strategies and the availability of new therapies during the last decades, formerly devastating chronic inflammatory diseases such as rheumatoid arthritis or systemic sclerosis (SSc) have become less menacing. However, in many patients, even state-of-the-art treatment cannot induce remission. Moreover, the risk for flares strongly increases once anti-inflammatory therapy is tapered or withdrawn, suggesting that underlying pathological processes remain active even in the absence of overt inflammation. It has become evident that tissues have the ability to remember past encounters with pathogens, wounds and other irritants, and to react more strongly and/or persistently to the next occurrence. This priming of the tissue bears a paramount role in defence from microbes, but on the other hand drives inflammatory pathologies (the Dr Jekyll and Mr Hyde aspect of tissue adaptation). Emerging evidence suggests that long-lived tissue-resident cells, such as fibroblasts, macrophages, long-lived plasma cells and tissue-resident memory T cells, determine inflammatory tissue priming in an interplay with infiltrating immune cells of lymphoid and myeloid origin, and with systemically acting factors such as cytokines, extracellular vesicles and antibodies. Here, we review the current state of science on inflammatory tissue priming, focusing on tissue-resident and tissue-occupying cells in arthritis and SSc, and reflect on the most promising treatment options targeting the maladapted tissue response during these diseases.

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“…A previous meta-analysis addressed this specific concern. Studies were included if rheumatoid arthritis or spondyloarthritis patients were in remission or in a LDA state [31]. This meta-analysis evaluated 13 controlled trials: 9 of rheumatoid arthritis and 4 of spondyloarthritis.…”

Section: Safety Of Taperingmentioning

confidence: 99%

Dose Tapering and Discontinuation of Biologic DMARDs in Axial Spondyloarthritis: A Narrative Review (2023 SPARTAN Annual Meeting Proceedings)

Chaudhary,

Bittar,

Daoud

et al. 2024

Curr Rheumatol Rep

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Purpose of Review Limited data is available for tapering or discontinuation of biologic therapy in patients with axSpA who are in disease remission. The current review concentrates on published studies regarding dose tapering or withdrawal of biologics in axSpA. Recent Findings Recent evidence in light of randomized controlled trials suggests that tapering of b-DMARDs is a feasible strategy to maintain remission or low disease activity in axSpA patients. TNF inhibitors were the studied biologics in most of these trials. The disease flare rates were comparable to those maintained on standard dose in most of these studies, although with variable tapering strategies and follow-up. Additionally, the duration of disease in remission prior to tapering, studied primary outcome, and flare definitions were heterogeneous. Female sex, HLA-B*27 negativity, high physician global score, and high CRP were negative predictors of successful tapering, but not consistently reported in all the trials. Although designed to address efficacy, there were no safety concerns with b-DMARD tapering. Withdrawal or complete discontinuation of biologics met with increased risk of flares compared to standard dosing. Summary Tapering of TNF inhibitors may be feasible in certain axSpA patients with an acceptable disease state; however, discontinuation is not currently recommended owing to increased risk of flare. Future studies with axSpA patients with longer remission duration prior to taper and different doses and types of b-DMARDs may provide more guidance.

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Impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and adverse events of special interest in patients with rheumatoid arthritis or spondyloarthritis: a systematic analysis of the literature and meta-analysis

Cited by 26 publications

References 45 publications

De-Escalation of Anti-Tumor Necrosis Factor Alpha Agents and Reduction in Adverse Effects: A Systematic Review

De-Escalation of Anti-Tumor Necrosis Factor Alpha Agents and Reduction in Adverse Effects: A Systematic Review

Inflammatory tissue priming: novel insights and therapeutic opportunities for inflammatory rheumatic diseases

Dose Tapering and Discontinuation of Biologic DMARDs in Axial Spondyloarthritis: A Narrative Review (2023 SPARTAN Annual Meeting Proceedings)

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