Elsevier

Autoimmunity Reviews

Volume 16, Issue 6, June 2017, Pages 650-657
Autoimmunity Reviews

Review
International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus

https://doi.org/10.1016/j.autrev.2017.04.011Get rights and content

Abstract

Background/purpose

Despite conventional immunosuppressants, active and steroid-dependent systemic lupus erythematosus (SLE) represents a therapeutic challenge. Only one biologic, belimumab, has been approved, but other biologics are sometimes used off-label. Given the lack of evidence-based data in some clinical situations encountered in real life, we developed expert recommendations for the use of biologics for SLE.

Methods

The recommendations were developed by a formal consensus method. This method aims to formalize the degree of agreement among experts by identifying, through iterative ratings with feedback, the points on which experts agree, disagree or are undecided. Hence, the recommendations are based on the agreed-upon points. We gathered the opinion of 59 French-speaking SLE experts from 3 clinical networks dedicated to systemic autoimmune diseases (FLEUR, IMIDIATE, FAI2R) from Algeria, Belgium, France, Italy, Morocco, Switzerland and Tunisia. Represented medical specialities were internal medicine (49%), rheumatology (34%), nephrology (7%), dermatology (5%), pediatrics (3%) and cardiology (2%). Two methodologists and 3 strictly independent SLE expert groups contributed to developing these recommendations: a steering group (SG) (n = 9), an evaluation group (EG) (n = 28) and a reading group (RG) (n = 22). Preliminary recommendations were drafted by the SG, then proposed to the EG. Each EG member rated the degree of agreement from 1 to 9 (1: lowest; 9: strongest) for each recommendation. After 2 rating rounds, the SG submitted a new version of the recommendations to the RG. With comments from the RG, the SG finalised the recommendations.

Results

A total of 17 final recommendations were formulated by the SG, considering all agreement scores and comments by the EG and RG members and the two methodologists. These recommendations define the subset of patients who require a biologic; the type of biologics to use (belimumab, rituximab, etc.) depending on the organ involvement and associated co-treatments; what information should be given to patients; and how to evaluate treatment efficacy and when to consider discontinuation.

Conclusion

Overall, 17 recommendations for the good use of biologics in SLE were formulated by a large panel of SLE experts to provide guidance for clinicians in daily practice. These recommendations will be regularly updated according to the results of new randomized trials and increasing real life experience.

Introduction

Systemic lupus erythematosus (SLE) is a severe systemic autoimmune disease that often represents a therapeutic challenge because of diverse manifestations, clinical course and prognosis. Patients with SLE are followed by different specialists because of several organ involvements, and treatments are tailored depending on the disease activity and/or severity of the organ involvement(s), comorbidities, side effects, drug interactions, drug availability, previous treatment and patient preference. Poorly controlled disease drives a vicious cycle, with organ damage undermining the long-term prognosis [1], [2], [3], triggered itself by persistent disease activity and particularly by corticosteroids abuse [4], [5], [6], [7], [8], [9], [10]. Hence, the main target in clinical practice is to prevent damage and maintain stable disease control with limited doses of corticosteroids [7], [11].

An evidence-based approach to therapy is desirable, but the actual benefit demonstrated by randomized controlled trials and cohort evaluations of biologics in SLE are still limited [10], [12]. Only one biologic, belimumab [13], has been approved to date, but other biologics are sometimes used off-label. The strategy of use of biologics remains a “grey area” in the literature [14], [15], [16], [17], [18], [19], [20], [21], [22] because of the limited evidence-based data and the wide range of situations encountered in real-life practice [10]. Opinions of highly qualified experts in SLE treatment are essential when data are absent or controversial.

Therefore, we established a set of expert recommendations for the use of biologics in SLE.

Section snippets

Literature search of available data

To assess the amount of available data, we searched for articles published up to June 2014. This search is synthetized in a published book in which most of the authors contributed. The book is presented in the Supplementary Information.

Definition of the recommendations scope

In light of the available literature, four clinical questions were defined: 1) Which patients might benefit from biologic therapy? 2) Which biologic and co-treatment might be used? 3) Which information should be given to patients? 4) How should the effectiveness

Results

For an overview of the recommendations development, see Table 1.

Discussion

A large panel of SLE experts formulated 17 recommendations for the good use of biologics in SLE to provide guidance for clinicians in daily practice.

The main advantages of the method to develop the recommendations are 1) the strict independence between the SG, which formulated proposals for voting, and the EG and RG, which judged the appropriateness of the proposals, thus avoiding one group as judge and jury; 2) the ability to identify the degree of agreement or indecision among experts by

Conclusion

We report 17 recommendations for the use of biologics in SLE that were developed with a formalized consensus of an international panel of experts. These recommendations are based on the most recent evidence in lupus management and discussions by a large and broadly international task force. The recommendations synthesize the current approaches to lupus treatment. The task force is convinced of the importance of disseminating these recommendations. It hopes that following these recommendations (

Take-home messages

  • 17 recommendations for the good use of biologics in SLE were formulated by a large panel of SLE experts.

  • These recommendations define:

    • the subset of patients who require a biologic

    • the type of biologics and co-treatment to use

    • what information should be given to patients

    • how to evaluate treatment efficacy and when to consider discontinuation.

Acknowledgments

These recommendations for the use of biologics in SLE were developed by multidisciplinary panels of experts on behalf of the Club Rhumatismes et Inflammation. French national networks focused on rare systemic autoimmune diseases contributed to this work by identifying SLE experts in France, Europe and North Africa and by the contribution of network-affiliated methodologists.

  • -

    FAI2R (Filière Nationale des Maladies Autoimmunes et Autoinflammatoires Rares), including 7 referee centres, 73

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    1

    On behalf of the Société Royale Belge de Rhumatologie/Koninklijke Belgische Vereniging voor Reumatologie (Belgian Society of Rheumatology), the Société Française de Rhumatologie (French Society of Rheumatology) and the Société Suisse de Rhumatologie (Swiss Society of Rheumatology), the CRI (Club Rhumatismes et Inflammation), FLEUR (Réseau Français du Lupus), IMIDIATE (Immune-Mediated Inflammatory Disease Alliance for Translational and Clinical Research) and FAI2R (Filière Nationale des Maladies Autoimmunes et Autoinflammatoires Rares) networks.

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