Low Prevalence of Anti-TNF-Induced Lupus in Patients With Inflammatory Bowel Disease

The incidence and clinical and serologic characteristics of anti-tumor necrosis factor (TNF)-induced lupus (ATIL) in patients with inflammatory bowel disease (IBD) were evaluated in a systematic review published in International Immunopharmacology.

Researchers used PubMed, Ovid Embase, Medline, and Cochrane CENTRAL databases from inception through April 2022 for studies describing ATIL in patients with IBD. Randomized clinical trials and prospective or retrospective cohort studies were included in the current analysis. Data on patient characteristics, anti-TNF treatment, and ATIL characteristics were collected from each study.

The primary outcome was the pooled ATIL incidence rate across study cohorts. Secondary outcomes included the pooled incidence rates of clinical symptoms and autoantibodies.

A total of 10 studies were selected for the analysis. The pooled ATIL incidence rate was 2.5% (95% CI, 1.5%-3.5%) among patients with IBD who received treatment with anti-TNF-α agents. Incidence was slightly higher in patients with Crohn disease (1.8% [0.8%-2.8%]) compared to patients with ulcerative colitis (1.5% [0.08%-2.2%]). Among patients receiving treatment with infliximab and adalimumab, the pooled ATIL incidence rates were 4.5% (2.9%-6.15%) and 0.2% (0.0%-0.3%), respectively.

Seven studies were included in the analysis of clinical symptoms. The most commonly reported symptoms were arthritis, fatigue, and mucocutaneous lesions. Among patients with confirmed ATIL, the pooled incidence rate of arthritis was 87.2% (95% CI, 78.5%-96.0%). The pooled incidence rates for fatigue and mucocutaneous lesions were 41.8% (95% CI, 17.0%-82.0%) and 29.4% (95% CI, 18.9%-39.8%), respectively. ATIL was also associated with cytopenia, fever, serositis, and renal involvement, though at lower incidence rates than other clinical symptoms. Patients with confirmed ATIL were also more likely to have certain autoantibodies. In patients with IBD and confirmed ATIL, the pooled incidence rate of antinuclear antibodies was 97.3%; the pooled incidence rate of antidouble stranded DNA (anti-dsDNA) antibodies was 73.9% (95% CI, 63.8%-83.9%).

Overall, ATIL was found to have a low incidence rate in patients with IBD and often resulted in arthritis, fatigue, and mucocutaneous lesions. In addition, patients with ATIL were more likely to develop antinuclear antibodies and anti-dsDNA antibodies.

Study limitations included the between-study heterogeneity; the small number of included studies; and the absence of data on concurrent immunomodulatory therapy, which may have affected ATIL risk.

“Further prospective investigations in larger patient cohorts may help refine questions regarding the incidence, the clinical characteristics, the serological characteristics and risk factors associated with the development of ATIL in patients with IBD treated with anti-TNF agents,” the study authors said.

Reference

Dai C, Wang YN, Tian WN, Huang YH, Jiang M. The incidence, clinical characteristics and serological characteristics of anti-tumor necrosis factor-induced lupus in patients with inflammatory bowel disease: a systematic review and meta-analysis. Int Immunopharmacol. Published online September 29, 2022. doi:10.1016/j.intimp.2022.109269