IL-6 blockade for Behçet's disease: review on 31 anti-TNF naïve and 45 anti-TNF experienced patients

Abstract

Objective. Despite the remarkable efficacy of anti-TNF agents in Behçet's disease (BD), unmet therapeutic needs for refractory or intolerant patients to these drugs still exist. Based on evidence implicating IL-6 in the pathogenesis of BD, we summarise the current experience on the off-label administration of the anti-IL-6 receptor antibody tocilizumab for BD refractory to disease-modifying anti-rheumatic drugs. Methods. We searched PubMed and EMBASE for original articles published through December 2021 reporting on the use of tocilizumab for BD. Results. We retrieved 25 articles fulfilling our search criteria, reporting on a total of 74 patients of whom 31 were anti-TNF naive; 2 additional anti-TNF experienced patients were included. The vast majority (72 of 76) received the standard intravenous dose of tocilizumab, whereas the total follow-up, including also post-treatment follow-up in many patients, ranged from 2 to 84 months without new safety issues. Tocilizumab was given in anti-TNF naive patients predominantly for vascular (n=16), central nervous system (n=7) and ocular involvement (n=5). On the other hand, anti-TNF experienced patients received tocilizumab predominantly for ocular (n=28), central nervous system (n=8) and mucocutaneous involvement (n=6). Tocilizumab was effective in 87% of anti-TNF naive (13 and 14 with complete and partial remission, respectively) and in 80% of anti-TNF experienced patients (17 and 19 with complete and partial remission, respectively). Conclusion. Although preliminary, evidence published so far suggests that IL-6 inhibition is a legitimate therapeutic option for BD patients with refractory ocular, CNS and vascular involvement. Controlled studies are clearly needed.

Association of high disease activity and serum IL-6 levels with the incidence of inflammatory major organ events in Behçet disease: a prospective registry study

“…However, considering the high incidence of inflammatory major organ events in patients with elevated serum IL-6 levels, even when using TNF inhibitors, therapy targeting IL-6 may be considered as a potential next step. As support for this, the efficacy of anti-IL-6 receptor antibodies have been recently reported to be effective against BD not only in TNF inhibitor naive patients, but even in TNF inhibitor-experienced patients (49,50).…”

Treat to target in Behcet's disease: Should we follow the paradigm of other systemic rheumatic diseases?

“…The above-mentioned questions/considerations should take into account that there has been a tremendous progress in the field of BD therapeutics, especially with the introduction of biologic targeted therapies in 2001 [97], which have changed the natural history of the disease, especially regarding the preservation of the best residual visual acuity [6,97,98]. Of note, newer biologic and targeted synthetic DMARDs are also tested with promising results in various aspects of BD [4,80,81,99].…”

Behçet’s Disease, Pathogenesis, Clinical Features, and Treatment Approaches: A Comprehensive Review

“…Behçet's disease is a complex disorder that affects various systems in the body, with varying clinical features from patient to patient [21]. The formation of these ulcers is thought to be due to a dysregulation of the immune system, leading to increased production of inflammatory cytokines such as TNF-alpha and IL-6, which damage the mucosal lining [22]. Almost all patients experience recurrent painful oral aphthous ulcers, typically the first symptom of the disease (Figure 1).…”

“…Behçet's illness was once thought to be a Th1-mediated inflammatory condition marked by elevated IFN-γ production. However, according to new research, Th17 cells-which also secrete IL-17 and IL-22-may be crucial in the illness [22,42,43]. Specialized antigen-presenting cells are assumed to be the driving force behind the formation of Th17 cells, which have been demonstrated to be pathogenic in numerous autoimmune and inflammatory disorders in humans [41].…”