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Efficacy and safety of steroid-sparing treatments in giant cell arteritis according to the glucocorticoids tapering regimen: A systematic review and meta-analysis

  • Anne-Laure Gérard
    Affiliations
    Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, UMR-S 1136, AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Département de Santé Publique, Paris, France
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  • Noémie Simon-Tillaux
    Affiliations
    Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, UMR-S 1136, AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Département de Santé Publique, Paris, France
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  • Youri Yordanov
    Affiliations
    Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, UMR-S 1136, AP-HP, Hôpital Saint-Antoine, Service d'Accueil des Urgences, Paris, France
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  • Patrice Cacoub
    Affiliations
    Sorbonne Université, INSERM U959, Immunopathology, Immunotherapies of autoimmunes and inflammatory diseases, RHU I2B, Labex Transimunom, AP-HP, Hôpital Pitié-Salpêtrière, Département de Médecine Interne et Immunologie Clinique, Paris, France, Centre national de référence Maladies Autoimmunes systémiques rares, Centre national de référence Maladies Auto-inflammatoires et Amylose, France
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  • Florence Tubach
    Affiliations
    Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, UMR-S 1136, AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Département de Santé Publique, Paris, France
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  • David Saadoun
    Affiliations
    Sorbonne Université, INSERM U959, Immunopathology, Immunotherapies of autoimmunes and inflammatory diseases, RHU I2B, Labex Transimunom, AP-HP, Hôpital Pitié-Salpêtrière, Département de Médecine Interne et Immunologie Clinique, Paris, France, Centre national de référence Maladies Autoimmunes systémiques rares, Centre national de référence Maladies Auto-inflammatoires et Amylose, France
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  • Agnès Dechartres
    Correspondence
    Corresponding author.
    Affiliations
    Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, UMR-S 1136, AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Département de Santé Publique, Paris, France
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Published:April 17, 2021DOI:https://doi.org/10.1016/j.ejim.2021.03.040

      Highlights

      • Tocilizumab is the only drug that reduces the relapse rate in giant cell arteritis.
      • Methotrexate was not significantly associated with a lower rate of relapse.
      • We did not find a significant interaction by glucocorticoids tapering regimen.
      • It seems important to standardize outcomes and glucocorticoids tapering regimen.

      Abstract

      Objectives

      To assess the efficacy and safety of adjuvant therapies in newly diagnosed or relapsing giant cell arteritis (GCA) in terms of relapse rate at week 52 (primary outcome) and to assess the impact of GC tapering regimen on adjuvant effectiveness.

      Methods

      For this systematic review and meta-analysis, we searched PubMed, EMBASE, CENTRAL, trial registries, from inception to November 2020. We included all randomized controlled trials (RCTs) and controlled prospective studies evaluating adjuvant treatments in GCA, without date or language restriction. Two reviewers independently selected studies, extracted data and assessed risk of bias. Quality of evidence was summarised with GRADE.

      Results

      Of the 680 records identified, 16 studies were included (1,068 participants) evaluating various adjuvant therapies compared to GC only. No study compared adjuvants with each other. Risk of bias was high in 5/7 trials evaluating our primary outcome. Risk of relapse at week 52 was reduced for only the anti-IL6 and IL6-receptor drug class versus the control (RR=0.45, 95%CI 0.30–0.66, I2=38%), particularly tocilizumab (RR=0.38, 95%CI 0.23–0.63, I2=42%) with a moderate quality of evidence. We found no significant interaction according to GC tapering regimen. Our meta-analysis did not show a significant benefit for methotrexate. Except for dapsone, ciclosporine and hydroxychloroquine, other adjuvants did not seem to show increased risk of adverse events.

      Conclusions

      Tocilizumab seems to reduce the relapse rate in GCA at week 52 but the quality of evidence was moderate. No other molecule has shown efficacy. No significant interaction on relapse rate by GC tapering regimen was found.

      Study registration

      PROSPERO CRD42020172011.

      Keywords

      Abbreviations:

      DMARD (disease-modifying antirheumatic drug), bDMARD (biologic disease-modifying antirheumatic drug), csDMARD (conventional synthetic disease-modifying antirheumatic drug), EULAR (European League Against Rheumatism), GC (glucocorticoid), GCA (giant cell arteritis), ICTRP (International Clinical Trials Registry Platform), IL (interleukin), IL6R (interleukin-6 receptor), IPD (individual patient data), ITT (intention to treat), ITTm (modified intention to treat), IV (intravenous), LOCF (last observation carried forward), NA (not available), PMR (polymyalgia rheumatica), phet (p-value heterogeneity), PO (by mouth), RCT (randomized controlled trial), RR (risk ratio), SMD (standardized mean difference), SC (subcutaneous), TNF (tumor necrosis factor)
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