Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases

Abstract

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

Impact of Anti-TNFα Treatment on the Humoral Response to the BNT162b2 mRNA COVID-19 Vaccine in Pediatric Inflammatory Bowel Disease Patients

“…In addition, concerning the exacerbation of IBD, some studies reported that the frequency of IBD flares after vaccination was low [ 20 , 36 ]. Reassuringly, a previous study of adult IBD patients also reported no IBD exacerbation was observed within 6 months after the initial vaccination, even in IBD patients with activity at baseline [ 37 ]. The present findings showed that all PIBD patients had no IBD exacerbation during the observation period, and these results are consistent with previously published studies in adults.…”

The accelerated waning of immunity and reduced effect of booster in patients treated with bDMARD and tsDMARD after SARS-CoV-2 mRNA vaccination

“…We found that b/tsDMARDs significantly reduce the duration of vaccine-induced protection in patients with both IA and IBD. These findings go hand in hand with various studies focusing on IBD or IA, yet not comparing these rheumatic and other autoinflammatory diseases (e.g., IBD) with respect to therapy ( 23 , 24 ). This reduced duration of the vaccine response was independent of underlying immune-mediated disease but clearly associated with the type of immunomodulation.…”

Complexity of the Immune Response Elicited by Different COVID-19 Vaccines, in the Light of Natural Autoantibodies and Immunomodulatory Therapies

“…It may be prescribed for the indication of moderate-to-severe plaque psoriasis, active enthesitis-related arthritis, active psoriatic arthritis, ankylosing spondylitis, active nonradiographic axial spondyloarthritis and objective signs of inflammation. The biological drug inhibiting tumor necrosis factor (TNFα) is an important treatment in a number of inflammatory conditions, including rheumatoid arthritis (RA), spondyloarthritis, psoriasis, hidradenitis suppurativa and inflammatory bowel disease (IBD) [ 44 , 45 ].…”

“…Anti-TNFα and IL-17 are drugs supplied with warnings about an increased risk of infections [ 44 , 47 , 48 ]. It has already been described that patients treated with anti-TNFα exhibited lower serologic responses one month and six months after vaccination (COVID-19 BNT162b2) compared to those not treated with anti-TNFα or to healthy controls (HCs) [ 44 ]. Additionally, compared with the placebo group, anti-TNFα-treated patients showed a moderate increase in susceptibility to upper respiratory infections (URIs) [ 49 ].…”