Guidelines for Biologics Use in Lupus by International Panel
The steering group approved 17 recommendations.
A multidisciplinary group of international experts has released recommendations for the use of biologics in patients with systemic lupus erythematosus (SLE), according to a summary recently published in Autoimmunity Reviews.1
Jacques-Eric Gottenberg, MD, PhD, from the rheumatology department at Strasbourg University Hospital in France, and colleagues formed a panel of 59 French-speaking experts on SLE from 7 countries who specialize in internal medicine (49%), rheumatology (34%), nephrology (7%), dermatology (5%), pediatrics (3%), and cardiology (2%).
The experts belonged to the Club Rhumatismes et Inflammations (CRI), a specialized section of the French Society for Rheumatology (SFR): Filière Nationale des Maladies Autoimmunes et Autoinflammatoires Rares FAI2R (FAI2R), Immune-Mediated Inflammatory Disease Alliance for Translational and Clinical Research (CRI-IMIDIATE), and French Lupus Network (FLEUR), which specialize in autoimmune diseases.
The panel formed a steering group of 9 experts, an evaluation group of 28 experts, and a reading group of 22 experts. The steering group approved 17 recommendations that sought to define which patients with SLE require treatment with a biologic, what type of biologic to use, what information to give patients, how to measure efficacy, and when to discontinue treatment.
“These recommendations are based on the most recent evidence in lupus management and discussions by a large and broadly international task force,” Dr Gottenberg and colleagues wrote in their study.
The researchers recommended performing a clinical evaluation and assessing factors, such as hydroxychloroquine blood levels, before concluding conventional treatment is ineffective. Patients can be prescribed a biologic if they have active or corticosteroid-dependent SLE and are treated with hydroxychloroquine, with a minimum of 2 successive immunosuppressive therapies such as methotrexate, cyclophosphamide, azathioprine, or mycophenolate mofetil.
Biologics should not be used in patients with SLE who have antiphospholipid syndrome but can be used in catastrophic cases, as well as in patients in whom autoimmune thrombocytopenia is associated with antiphospholipid syndrome. The panel concluded that biologics should not be used during pregnancy, except in extreme cases, and a fetal echography should be performed if a patient with SLE is exposed to a biologic during pregnancy. If a patient has both rheumatoid arthritis and SLE, the panel recommends using anti-tumor necrosis factor (anti-TNF) therapy — abatacept, rituximab, or tocilizumab — while keeping in mind the risks of SLE flare and neutropenia with anti-TNF therapy and tocilizumab, respectively.
Dr Gottenberg and colleagues also recommended the following biologic treatments and co-treatments:
- Belimumab, in cases of refractory and corticosteroid-dependent disease forms, in the absence of kidney or central nervous system involvement or severe autoimmune thrombocytopenia
- Rituximab, as a first biologic in cases of refractory and corticosteroid-dependent forms of kidney or central nervous system involvement or severe autoimmune thrombocytopenia
- Biologics do not need to be associated with a conventional immunosuppressant
- Two immunomodulatory biologics should not be combined
To evaluate the efficacy of biologic use, the panel members set therapeutic goals at 6 months of a decrease in disease activity by a validated disease activity score and discontinuation or significantly decreased dosage of oral corticosteroids. During monitoring, clinicians should use validated scores to evaluate disease activity, assess biologic tolerance, analyze the safety profile, and discontinue treatment if adverse events occur. Specifically, the researchers recommended evaluating biologic safety at 1-month, 3-month, and 6-month follow-up, with a biannual evaluation by an SLE specialist if biologic use persists for more than 6 months.
Summary & Clinical Applicability
To improve the management of patients with refractory SLE and to guide clinicians in the choice of treatments, new international recommendations for the use of biologics in Systemic Lupus Erythematosus (SLE) have been developed by 61 multidisciplinary SLE experts from 7 countries (France, Belgium, Switzerland, Italy, Morocco, Tunisia and Algeria). These recommendations are based on the most recent evidence in SLE management. The formal consensus methodology (eg, formalizing the degree of agreement though individual iterative ratings with feedbacks) was used.
Seventeen recommendations define:
- The subset of patients who require a biologic
- The type of biologic and co-treatment to use
- What information should be given to patients
- How to evaluate treatment efficacy and when to consider discontinuation.
The content of these recommendations concerned refractory SLE definition (eg, previous treatments, adherence, and corticosteroids dependence level), biologic and co-treatment choice for different SLE manifestation (eg, joint, renal, neurological, haematological), specific situations during SLE (eg, contraception, pregnancy, vaccinations, associated anti-phospholipid syndrome) and suggest how and when to evaluate the biologic's efficacy (eg, time period and corticosteroids sparing level). The experts also discussed the interest of some off-label biologics, including ritiximab, in some refractory situations.
These recommendations were endorsed by Belgian, French and Swiss Societies for Rheumatology.
These recommendations will be regularly updated according to the results of forthcoming randomized controlled trials and increasing real-life experience.
Limitations & Disclosures
Dr Gottenberg and colleagues noted the recommendations are mainly targeted toward specialists and not general physicians, and the recommendations were formed by specialists involved in the daily care of patients with SLE, rather than patient representatives.
- Kleinmann J-F, Tubach F, Guern VL, et al. International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus [published online April 18, 2017]. Autoimmun Rev. doi:10.1016/j.autrev.2017.04.011