Paradoxical reactions under TNF-α blocking agents and other biological agents given for chronic immune-mediated diseases: an analytical and comprehensive overview

Abstract

Paradoxical adverse events (PAEs) have been reported during biological treatment for chronic immune-mediated diseases. PAEs are defined as the occurrence during biological agent therapy of a pathological condition that usually responds to this class of drug. A wide range of PAEs have been reported including dermatological, intestinal and ophthalmic conditions, mainly with antitumour necrosis factor α (TNF-α) agents. True PAEs include psoriasis, Crohn's disease and hidradenitis suppurativa. Other PAEs may be qualified as borderline and include uveitis, scleritis, sarcoidosis and other granulomatous diseases (granuloma annulare, interstitial granulomatous dermatitis), vasculitis, vitiligo and alopecia areata. Proposed hypotheses to explain these PAEs include an imbalance in cytokine production, the differential immunological properties between the monoclonal antibodies and TNF-α soluble receptor, an unopposed type I interferon production and a shift towards a Th1/Th2 profile. Data from registries suggest that the risk for paradoxical psoriasis is low and non-significant. We discuss management of these PAEs, which depends on the type and severity of the adverse events, pre-existing treated conditions and the possibility of alternative therapeutic options for the underlying disease. Paradoxical adverse events are not restricted to anti-TNF-α agents and close surveillance of new available biological drugs (anti-interleukin-17/23, anti-integrin) is warranted in order to detect the occurrence of new or as yet undescribed events.

Comparative Evaluation of the Long-Term Efficacy and Safety of the Infliximab Biosimilar BCD-055 and Reference Infliximab in Patients With Ankylosing Spondylitis: Results of the International Multicenter Randomized Double-Blind Phase Iii Clinical Study Asart-2

“…Аналогичная дина-мика стандартных индексов активности АС (BASDAI, MASES), функциональных наруше-ний (BASMI, BASFI) и показателей качества жизни (SF-36) установле-на как между исследуемыми препа-ратами BCD-055 и РЕМ, так и в сравнении с результатами ис-следований ASSЕRT и PLANETAS [20][21][22][23][24]. Все выявленные в ходе иссле-дования препарата BCD-055 НР яв-ляются ожидаемыми, отражены в инструкции по медицинскому применению РЕМ и по частоте и спектру соответствуют ранее опубликованным данным по рефе-рентному препарату [20,[24][25][26][27][28][29][30][31][32][33]. В рамках данного исследования на протяжении 54 нед лечения разли-чий в профиле безопасности изучае-мого биоаналога и РЕМ также не ус-тановлено.…”

Comparative efficacy and safety of infliximab biosimilar (BCD-055) and innovator infliximab in patients with ankylosing spondylitis (results of international, multiple-center, double-blind phase I and phase III clinical studies)

“…ИФНα также является индукто-ром некоторых рецепторов хемокинов на Т-клетках (CXCR3), которые индуцируют миграцию Т-клеток в кожу, тем самым поддерживая хроническое воспаление [22][23][24].…”

Paradoxical Nodular Scleritis during Tocilizumab Therapy: A Case Report

“…This may be further subclassified into true reactions: for example, the onset of de novo psoriasis during RTX therapy (or in parallel -the exacerbation of a preexisting condition upon starting a biological agent), or borderline reactions. The latter exist when a biological agent has a theoretical rationale for its efficacy in treating a certain condition (but is not registered for it), yet gives rise to the development of that condition 1 .…”

“…Paradoxical reactions may be defined as "the occurrence with therapy with a biological agent, of a pathological condition that usually responds to this class of drug 1 ." This may be further subclassified into true reactions: for example, the onset of de novo psoriasis during RTX therapy (or in parallel -the exacerbation of a preexisting condition upon starting a biological agent), or borderline reactions.…”