Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients

Abstract

Background and aims Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-TNF level influences serological responses, remains unknown. Methods Seroprevalence and the magnitude of SARS-CoV-2 nucleocapsid antibody responses were measured in surplus serum from 11422 (53.3% (6084) male; median age 36.8 years) patients with immune-mediated inflammatory diseases, stored at six therapeutic drug monitoring laboratories between 29 th January and 30 th September 2020. Data were linked to nationally-held SARS-CoV-2 PCR results to 4 th May 2021. Results Rates of PCR confirmed SARS-CoV-2 infection were similar across treatment groups. Seroprevalence rates were lower in infliximab- and adalimumab- than vedolizumab-treated patients (infliximab: 3.0% (178/5893), adalimumab: 3.0% (152/5074), vedolizumab: 6.7% (25/375), p = 0.003). The magnitude of SARS-CoV-2 reactivity was similar in infliximab- vs adalimumab-treated patients (median 4.30 cut-off index (COI) (1.94 – 9.96) vs 5.02 (2.18 – 18.70), p = 0.164), but higher in vedolizumab-treated patients (median 21.60 COI (4.39 - 68.10, p< 0.004). Compared to patients with detectable infliximab and adalimumab drug levels, patients with undetectable drug levels (<0.8 mg/L) were more likely to be seropositive for SARS-CoV-2 antibodies. One-third of patients who had PCR testing prior to antibody testing failed to seroconvert, all were anti-TNF treated. Subsequent positive PCR-confirmed SARS-CoV-2 was seen in 7.9% (12/152) patients after a median time of 183.5 days (129.8 – 235.3), without differences between drugs. Conclusion Anti-TNF treatment is associated with lower SARS-CoV-2 nucleocapsid seroprevalence and antibody reactivity when compared to vedolizumab-treated patients. Higher seropositivity rates in patients with undetectable anti-TNF levels supports a causal relationship, although confounding factors, such as combination therapy with immunomodulator, may have influenced the results.

Therapies for inflammatory bowel disease do not pose additional risks for adverse outcomes of SARS‐CoV‐2 infection: an IG‐IBD study

“…On one hand, this decision could be supported by evidence of a lower serological response to vaccines or natural infection, related to either IBD itself 15 or IBD therapies, namely anti‐TNF agents. 16 , 17 On the other hand, if priority access is granted to people at higher risk of adverse COVID‐19 outcomes, should this apply to some or all IBD patients? To answer this question, this observational study investigated risk factors for adverse COVID‐19 outcomes in a large, nation‐wide cohort of IBD patients, and used multivariable analyses to build indices to identify patients at the relatively highest risk.…”

Vaccination against SARS-CoV-2 in Patients with Inflammatory Bowel Diseases: Where Do We Stand?

“…As a result, little is known about the effectiveness, side-effects, and safety of SARS-CoV-2 vaccination in IBD patients, especially in the case of required immunosuppressive therapies. Recent studies revealed attenuated immune responses to SARS-CoV-2 infection in patients treated with immunomodulating therapies (e.g., anti-TNF agents), suggesting an attenuated immune response following vaccination [14].…”

Perspectives on Subcutaneous Infliximab for Rheumatic Diseases and Inflammatory Bowel Disease: Before, During, and After the COVID-19 Era

“…Protective immunity and vaccination will be critical to ending the COVID-19 pandemic, and a global vaccination programme is underway. Some evidence suggests TNF inhibitors may impair immune responses to pneumococcal, influenza, and viral hepatitis vaccinations [ 97 ]; thus, it is important to understand their impact in the context of COVID-19. The UK-based CLARITY study has shown that infliximab attenuated the serological response after natural infection, finding an inverse relationship between infliximab trough levels and seroconversion [ 84 , 97 ].…”

“…Some evidence suggests TNF inhibitors may impair immune responses to pneumococcal, influenza, and viral hepatitis vaccinations [ 97 ]; thus, it is important to understand their impact in the context of COVID-19. The UK-based CLARITY study has shown that infliximab attenuated the serological response after natural infection, finding an inverse relationship between infliximab trough levels and seroconversion [ 84 , 97 ]. Lower seroconversion rates in infliximab-treated patients were also noted after a single SARS-CoV-2 vaccine dose, which could increase the likelihood of recurrent SARS-CoV-2 infection in affected patients [ 97 ].…”

“…The UK-based CLARITY study has shown that infliximab attenuated the serological response after natural infection, finding an inverse relationship between infliximab trough levels and seroconversion [ 84 , 97 ]. Lower seroconversion rates in infliximab-treated patients were also noted after a single SARS-CoV-2 vaccine dose, which could increase the likelihood of recurrent SARS-CoV-2 infection in affected patients [ 97 ]. However, it is important to view these findings in the context of the similar or reduced risk of severe COVID-19 with anti-TNF treatment, as discussed previously [ 76 – 81 ].…”