Paradoxical reactions and biologic agents: a French cohort study of 9303 patients

Abstract

Background Paradoxical reactions (PRs) are defined as the occurrence during biologic therapy of a pathological condition that usually responds to these drugs. Objectives To estimate the incidence of PRs and identify risk factors. Methods Multicentre study of the database for the Greater Paris University Hospitals, including biologic-naive patients receiving anti-tumour necrosis factor-a, anti-interleukin-12/23, anti-interleukin-17 or anti-a4b7-integrin agents for psoriasis, inflammatory rheumatism or inflammatory bowel disease (IBD). We used natural language processing algorithms to extract data. A cohort and a case-control study nested in the cohort with controls selected by incidence density sampling was used to identify risk factors. Results Most of the 9303 included patients (median age 43Á0, 53Á8% women) presented an IBD (3773, 40Á6%) or a chronic inflammatory rheumatic disease (3708, 39Á9%), and 8489 (91Á3%) received anti-TNF-a agents. A total of 297 (3Á2%) had a PR. The global incidence rate was 7Á6 per 1000 person-years [95% confidence interval (CI) 6Á8-8Á5]. The likelihood of PR was associated with IBD [adjusted odds ratio (aOR) 1Á9, 95% CI 1Á1-3Á2, P = 0Á021] and a combination of at least two inflammatory diseases (aOR 6Á1, 95% CI 3Á6-10Á6, P < 0Á001) and was reduced with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and corticosteroids (aOR 0Á6, 95% CI 0Á4-0Á8, P = 0Á002; and OR 0Á4, 95% CI 0Á2-0Á6, P = 0Á002, respectively). Conclusions The likelihood of PRs was associated with IBD or a combination of a least two inflammatory diseases. More studies are needed to assess the benefit of systematically adding csDMARDs for such high-risk patients.What is already known about this topic?• Most published studies about paradoxical reactions concern paradoxical psoriasis in patients receiving anti-tumour necrosis factor-a agents. • Few data are available for other paradoxical reactions and the most recent biologics.What does this study add?• Risk of paradoxical reactions was increased with inflammatory bowel disease and a combination of at least two inflammatory diseases.

Injuries and child abuse increase during the pandemic over 12942 emergency admissions

“…The French coding system for medical activity, based on the Programme de Médicalisation des Systèmes d'Information (PMSI) database, is satisfactory in terms of consistency, accuracy and exhaustivity for hospitalized patients [ 8 , 11 ]. The AP-HP central medical data warehouse (EDS) is reliable tool for screening diagnostic codes, as previously reported [12][13][14] . Regarding the identification of child abuse and neglect victims, one encouraging perspective is the exploration of the national French claims database (Système National des Données de Santé, SNDS) and its connection with clinical databases such as the EDS.…”

Pyoderma gangrenosum following anti-TNF therapy in chronic recurrent multifocal osteomyelitis: drug reaction or cutaneous manifestation of the disease? A critical review on the topic with an emblematic case report

“…From a dermatologic perspective the onset of a PG or PG-like lesions during anti-TNF therapy often pose a diagnostic and therapeutic challenge, as it is hard to discriminate between a natural history of the disease (in most cases patients use the anti-TNF agent for diseases classically associated to PG) or an adverse “paradoxical” reaction to this class of drug, as TNF inhibitors represent a therapeutic option for PG itself ( 9 ).…”

“…Anti TNF-α cutaneous paradoxical reaction are rare events, mainly characterized by psoriasiform eruption (especially palmo-plantar and pustular lesions) in up to 75% of the cases, and to a lesser extent by sarcoidosis and HS ( 9 , 76 ). A recent review on drug-induced PG, basing on the Naranjo algorithm, critically analysed the role of different class of drugs in the dermatosis onset, concluding that anti-TNF agents were weakly associated to drug-induced PG (mean Naranjo score between 1 and 4, indicating only a possible adverse reaction) ( 77 ).…”

The use of large patient databases to improve disease understanding and care

“…Paradoxical psoriasis results from an exaggerated innate immune response orchestrated by plasmacytoid dendritic cells producing type I interferon, as demonstrated by Conrad et al 1 In this issue of the British Journal of Dermatology, Bataille et al have investigated the incidence and risk factors for paradoxical reactions to biologic agents in a cohort of patients identified from the database of the 39 university hospitals of the Paris region. 2 This database contains outpatient and inpatient medical records from more than 11 million patients followed up since 2012. Using an innovative approach including algorithms based on natural language processing, the authors were able to analyse medical records to constitute a cohort of more than 9000 patients treated with a biologic agent, out of whom 297 experienced a paradoxical reaction.…”

“…In this issue of the British Journal of Dermatology , Bataille et al . have investigated the incidence and risk factors for paradoxical reactions to biologic agents in a cohort of patients identified from the database of the 39 university hospitals of the Paris region 2 . This database contains outpatient and inpatient medical records from more than 11 million patients followed up since 2012.…”