Systematic review and meta-analysis of dermatological reactions in patients with inflammatory bowel disease treated with anti-tumour necrosis factor therapy

Abstract

Aim The role of anti-tumour necrosis factor (TNF) medications in inflammatory bowel disease (IBD) is now established. Recent studies have reported the incidence of dermatological adverse events with use of anti-TNFs in IBD. The aim of this study was to investigate the incidence of dermatological reactions in patients on anti-TNF therapy for IBD. Methods We searched MEDLINE, the Cochrane Library and EMBASE to identify studies reporting any dermatological reaction in patients exposed to anti-TNF for treatment of IBD. The incidence of dermatological complications in the entire review population was pooled by meta-analysis of data from individual studies using the random effects model. Pooled estimates in male and female patients and in patients treated with different anti-TNF agents were also calculated. We applied mixed effects (methods of moments) regression models to investigate between-study heterogeneity. Results Forty-eight studies reporting a total of 29 776 patients treated with anti-TNF medications for IBD were identified. Gender distribution was available for 18 960 participants with 45.3% females. Data on type of disease were available for 20 226 patients: 74.9% (n = 15 154) Crohn’s disease, 24.2% (n = 4901) ulcerative colitis and 0.9% (n = 171) IBD-unclassified. The type of anti-TNF used was mentioned for 17 085 individuals: 67.5% (n = 11 530) infliximab (IFX), 30.5% (n = 5203) adalimumab (ADA), 1.7% (n = 296) certolizumab and 0.3% (n = 56) golimumab. The pooled incidence of any dermatological reaction from 26 studies was 19.4% [95% confidence interval (CI): 15.2–24.4]. The pooled incidence for IFX and ADA was 23.7% (95% CI: 17.8–30.8) from 12 studies and 33.3% (95% CI 18.8–51.1) from seven studies, respectively. We found a trend of increased event rate with increasing percentage of male population (P = 0.08). The commonest reported event (39 studies) was psoriasis/psoriasiform rash with a pooled incidence of 5.6% (95% CI: 4.2–7.4). The incidence of psoriasis/psoriasiform rashes for IFX and ADA was 6.1% (95% CI 3.4–10.6) from 15 studies and 5.9% (95% CI: 2.5–13.5) from seven studies, respectively. Other reactions reported included eczema with a pooled incidence of 5.5% (95% CI: 3.3–8.9) from 17 studies and skin infections with pooled incidence of 7.9% (95% CI: 5.5–11.2) from 11 studies. Conclusion The incidence of dermatological events in patients with IBD treated with anti-TNF medications is high. The most commonly reported reaction is psoriasis/psoriasiform reaction. Clinicians should be vigilant to dermatological side effects following treatment of IBD with anti-TNF.

Incidence of and Risk Factors for Paradoxical Psoriasis or Psoriasiform Lesions in Inflammatory Bowel Disease Patients Receiving Anti-TNF Therapy: Systematic Review With Meta-Analysis

“…At present, paradoxical psoriasis or psoriasiform lesions can no longer be considered rare in clinical routine, with incidence estimates of greater than 20% with the use of anti-TNF agents in some research. For the incidence of psoriasis/psoriasiform rash, our results, overall, were comparable to the results from the 2021 meta-analysis ( 43 ). The primary outcome of dermatological reactions in IBD patients receiving anti-TNF therapy from 26 studies was 19.4% (95% CI: 15.2–24.4%, I 2 = 95%) in this meta-analysis.…”

Dermatological Manifestations in Inflammatory Bowel Diseases

“…In particular, in the last few years, anti-TNF-α agents used in IBDs have been increasingly reported to induce mucocutaneous side effects. TNF-α-antagonist-induced skin lesions include adverse mucocutaneous reactions, infectious complications, and skin cancers [ 67 , 68 , 69 ] ( Table 2 ).…”

De-Escalation of Anti-Tumor Necrosis Factor Alpha Agents and Reduction in Adverse Effects: A Systematic Review

“…In a recent meta-analysis including patients with IBD treated with anti-TNF-α agents, the pooled incidence of any dermatological reaction was 19% (95% confidence interval (CI) [15][16][17][18][19][20][21][22][23][24], with psoriasis or psoriasiform rash being the most common [8]. The pathophysiology of this paradoxical adverse effect is not completely clear; however, a local increase in interferon alpha (because its release is no longer inhibited by TNF-α) and genetic predisposition may play a role [9].…”

“…The pathophysiology of this paradoxical adverse effect is not completely clear; however, a local increase in interferon alpha (because its release is no longer inhibited by TNF-α) and genetic predisposition may play a role [9]. Other associated dermatological adverse effects include injection/infusion site reactions (caused by allergic hypersensitivity reactions and/or local trauma), eczema (possibly caused by an imbalance in the type 1 and 2 helper T cell response), and skin infections [8][9][10][11][12]. In a meta-analysis focusing on patients with RA, psoriatic arthritis, and ankylosing spondylitis, 30.8% of the anti-TNF-α users had at least one infection during follow-up.…”