Paradoxical effects of anti-TNF-α agents in inflammatory diseases

Abstract

Anti-TNF agents represent a major breakthrough in the management of inflammatory diseases. Among the side effects of these agents are the so-called paradoxical effects described in this review. They represent new onset or exacerbation of a condition (symptom/disease), usually improved with TNF blockers. These paradoxical effects are mainly psoriasiform skin reactions, uveitis and granulomatous diseases (such as sarcoidosis and Crohn's disease). Infrequent and probably underreported, they should be discussed from the viewpoint of spontaneous features of the underlying disease (e.g., uveitis or psoriasis in a case of spondyloarthritis). The causal mechanism of occurrence is still a matter of debate, but may implicate an imbalance of cytokines toward interferons, chemokines and probably IL-17. These reactions may raise differential diagnosis problems. Symptoms resolve, most of the time, due to the discontinuation of the anti-TNF agent or sometimes a switch to another TNF blocker; but in some cases, it is a class effect that could lead to the withdrawal of all anti-TNF agents.

Keywords::

• anti-TNF agents
• Crohn's disease
• paradoxical effect
• psoriasis
• sarcoidosis
• TNF-α
• uveitis
• vasculitis

Financial & competing interests disclosure

D Wendling has received speaking fees and/or consultancy fees from Abbott, MSD, Pfizer, Roche Chugai, BMS, Amgen, Nordic Pharma and Swedish Orphan Biovitrum, and grants from Abbott, MSD, Pfizer, Roche Chugai and BMS. D Wendling is also National co-ordinator of the study, CAIN 457F2305 (secukinumab in AS, Novartis) and National co-ordinator and investigator of the study ALIGN (sarilumab in AS, Sanofi-Aventis). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Paradoxical effects of anti-TNF agents are defined as manifestations occurring under anti-TNF agents.

• Mainly occur while the underlying disease motivating TNF blockers is controlled.

• Temporal relationship of resolution after discontinuation of the TNF blockers and positive rechallenge test are arguments for a direct responsibility of anti-TNF agents.

• The possibility of a feature of the underlying disease and the occurrence of this kind of effect under other treatments may represent arguments against a paradoxical effect.