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We used natural language processing algorithms to extract data. A cohort and a case\u2013control study nested in the cohort with controls selected by incidence density sampling was used to identify risk factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Most of the 9303 included patients (median age 43\u00b70, 53\u00b78% women) presented an IBD (3773, 40\u00b76%) or a chronic inflammatory rheumatic disease (3708, 39\u00b79%), and 8489 (91\u00b73%) received anti-TNF-\u03b1 agents. A total of 297 (3\u00b72%) had a PR. The global incidence rate was 7\u00b76 per 1000 person-years [95% confidence interval (CI) 6\u00b78\u20138\u00b75]. The likelihood of PR was associated with IBD [adjusted odds ratio (aOR) 1\u00b79, 95% CI 1\u00b71\u20133\u00b72, P = 0\u00b7021] and a combination of at least two inflammatory diseases (aOR 6\u00b71, 95% CI 3\u00b76\u201310\u00b76, P &amp;lt; 0\u00b7001) and was reduced with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and corticosteroids (aOR 0\u00b76, 95% CI 0\u00b74\u20130\u00b78, P = 0\u00b7002; and OR 0\u00b74, 95% CI 0\u00b72\u20130\u00b76, P = 0\u00b7002, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><jats:p>What is already known about this topic? \u00a0Most published studies about paradoxical reactions concern paradoxical psoriasis in patients receiving anti-tumour necrosis factor-\u03b1 agents.Few data are available for other paradoxical reactions and the most recent biologics.<\/jats:p><jats:p>What does this study add? \u00a0Risk of paradoxical reactions was increased with inflammatory bowel disease and a combination of at least two inflammatory diseases.Risk of paradoxical reactions was reduced with conventional synthetic disease-modifying antirheumatic drugs or corticosteroid therapy, which could be added for high-risk 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