Clinical Features of Drug-Induced Lupus in Patients With IBD Treated With Anti-TNF-α Therapy

Abstract

Introduction: Tumor necrosis factor-α (TNF-α) has a central role in the pathogenesis of the mucosal inflammation of both Crohn’s disease (CD) and ulcerative colitis (UC). Infliximab (IFX) and adalimumab (ADA) are anti-TNF-α-antibodies, and certolizumab pegol (CZP) is a pegylated humanized Fab’ fragment directed against TNF-α. These medications may lead to the development of other immunemediated phenomena. We sought to examine our experience with the development of drug-induced lupus (DLE) associated with anti-TNF-α therapy in patients with inflammatory bowel disease (IBD). Methods: We performed a retrospective review of patients with IBD and DLE attributable to anti-TNF-α therapy at a tertiary care IBD center between January 1, 2000 and January 31, 2014. The DLE diagnosis was considered in cases that showed: (1) a temporal relationship between anti-TNF-α therapy and clinical manifestations; (2) at least 1 serologic American congress of rheumatology (ACR) criteria of SLE (e.g., antinuclear antibodies [ANA], anti-double-stranded-DNA [dsDNA] antibodies); and (3) at least 1 nonserologic ACR criteria (e.g., arthritis, malar rash). Results: Of 1,440 IBD patients who were identified by a database search engine as having been on anti-TNF-α medications, 55 were found to have developed DLE (3.8%). Median age at DLE diagnosis was 43 years (range, 15-67), and 87% were female. Forty patients had CD (72%), 11 had UC (20%), and 4 had indeterminate colitis (IC, 8%). Forty patients (72%) originally were treated with IFX, 12 (22%) were treated with ADA, and 3 (6%) were treated with CZP. DLE occurred after median anti-TNF-α treatment duration of 1.1 years (range, 0.1-9). Features of DLE included arthritis in 43 patients (78%), lupus malar rash in 6 patients (11%), and non-scarring alopecia in 4 (0.1%). ANA were positive in 32 patients (94% of those tested), anti-dsDNA antibodies in 32 (76% of those tested), and anti-histone antibodies in 15 (62% of those tested). All but 1 patient improved after stopping anti-TNF-α therapy. Twenty-nine patients were treated with corticosteroids after DLE diagnosis. The median time to resolution of DLE symptoms post-DLE diagnosis was 1 month (range, 1-12). Twenty-two of 55 patients (40%) received an alternative TNF-α inhibitor (IFX, 2; ADA, 10; and CZP, 10 patients). Five of these patients had another episode of DLE, while 17 tolerated the second anti-TNF-α without recurrence of DLE. Conclusion: The overall frequency of DLE among IBD patients on anti-TNF-α therapy was low. DLE was managed with discontinuation of anti-TNF-α medications, and in some cases corticosteroids. The majority of the patients who were switched to another anti-TNF-α therapy tolerated it.