A Systematic Review of the Off-Label Use of Biological Therapies in Systemic Autoimmune Diseases

Abstract

In 2006, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the BIOGEAS project, a multicenter study devoted to collecting data on the use of biological agents in adult patients with systemic autoimmune diseases (SAD). The information source is a periodic surveillance of reported cases by a MEDLINE search (last update before this writing: December 31, 2007). The analysis included a total of 19 SAD and 6 biological agents. By December 31, 2007, the Registry included 1370 patients with SAD who had been treated with biological agents (562 received infliximab, 463 rituximab, 285 etanercept, 42 anakinra, and 18 adalimumab). SAD included Sjögren syndrome (SS; 215 cases), Wegener granulomatosis (261 cases), sarcoidosis (219 cases), systemic lupus erythematosus (SLE; 172 cases), Behçet disease (173 cases), adult-onset Still disease (118 cases), cryoglobulinemia (88 cases), and other diseases (80 cases). The higher rate of therapeutic response was found for the use of rituximab in patients with SLE (90%), SS (91%), antiphospholipid syndrome (92%), and cryoglobulinemia (87%); infliximab in sarcoidosis (99%), adult-onset Still disease (90%), and polychondritis (86%); and etanercept in Behçet disease (96%). Results from controlled trials showed lack of efficacy for the use of infliximab in SS and etanercept in SS, Wegener granulomatosis, and sarcoidosis. In addition, an excess of side effects (>50% of reported cases) was observed for the use of infliximab in inflammatory myopathies and sarcoidosis, and for the use of etanercept in polymyositis. Sufficient data are not yet available to evaluate fully the efficacy and safety of adalimumab and anakinra in patients with SAD. In conclusion, current scientific evidence on the use of biological therapies in patients with SAD is mainly based on uncontrolled, observational data. The best results have been observed in the use of rituximab for SS, SLE, and cryoglobulinemia; infliximab for sarcoidosis and adult-onset Still disease; and etanercept for Behçet disease. Lack of efficacy was demonstrated for infliximab and etanercept in SS, for etanercept in Wegener granulomatosis and sarcoidosis, and for anti-tumor necrosis factor (TNF) in SS. Future controlled trials are needed to confirm the potential use of biological therapies in patients with SAD.

Immunopathogenesis Based Adamantiades- Behcet Disease Vasculitis Treatment

“…Different results were reported from the Study Group on Autoimmune Diseases (GEAS), who published an impressive rate of response in ABD using etanercept (96%), (Ramos-Casals et al, 2008). These contradictory results indicate that more studies need to be undertaken in order to assess etanercept in ABD.…”

The Off-Label Use of Rituximab for the Management of Inflammatory Disorders: American University of Beirut Medical Center Experience

“…Although Merrill et al 12 showed no difference in primary or secondary end points between placebo and rituximab treatment over 52 weeks of treatment in patients with moderate-to severe SLE in the EXPLORER trial, other studies have shown more promising results. Ramos-Casals et al 8 in 2008 showed that the best results were observed in the use of rituximab for Sjögren's syndrome, SLE, and cryoglobulinemia. A recent review suggested that rituximab induces B-cell depletion in 95% of patients, and a significant reduction in disease activity is achieved with a relatively good safety profile in patients with SLE 7 However, there is always a difficulty in assessing the status of SLE patients and response rate in any research, given the heterogeneity of the disease.…”

“…This poses multiple questions on when and how to use these agents, since there are no current recommendations or guidelines on their use in such circumstances. 8 B cells play important roles in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, SLE, and Sjögren's syndrome. They exert their pathogenic effect by producing autoantibodies which target self antigens and induce inflammation and tissue injury, disrupting T cell tolerance, activating autoreactive memory T cells, attracting and activating dendritic cells, inhibiting regulatory T cells, and recruiting follicular B-helper T cells, among many other functions.…”

Abdominal Pain, Flank Pain, Blurry Vision, and Lower Extremity Weakness in a 16‐Year‐Old Female

“…For TMA, high-dose steroids, intravenous immunoglobulin, and/or plasmapheresis may be tried (25,28). Case reports suggest a beneficial effect of rituximab, a monoclonal B cell-depleting antibody, in severe APS (52). A phase II trial has shown safety and tolerability of rituximab in patients with APS (53).…”