Response to Vaccines in Patients with Immune-Mediated Inflammatory Diseases: A Narrative Review

Abstract

Patients with immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and inflammatory bowel disease, are at increased risk of infection. International guidelines recommend vaccination to limit this risk of infection, although live attenuated vaccines are contraindicated once immunosuppressive therapy has begun. Biologic therapies used to treat IMIDs target the immune system to stop chronic pathogenic process but may also attenuate the protective immune response to vaccines. Here, we review the current knowledge regarding vaccine responses in IMID patients receiving treatment with biologic therapies, with a focus on the interleukin (IL)-12/23 inhibitors. B cell-depleting therapies, such as rituximab, strongly impair vaccines immunogenicity, and tumor necrosis factor (TNF) inhibitors and the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) fusion protein abatacept are also associated with attenuated antibody responses, which are further diminished in patients taking concomitant immunosuppressants. On the other hand, integrin, IL-6, IL-12/23, IL-17, and B-cell activating factor (BAFF) inhibitors do not appear to affect the immune response to several vaccines evaluated. Importantly, treatment with biologic therapies in IMID patients is not associated with an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or developing severe disease. However, the efficacy of SARS-CoV-2 vaccines on IMID patients may be reduced compared with healthy individuals. The impact of biologic therapies on the response to SARS-CoV-2 vaccines seems to replicate what has been described for other vaccines. SARS-CoV-2 vaccination appears to be safe and well tolerated in IMID patients. Attenuated but, in general, still protective responses to SARS-CoV-2 vaccination in the context of certain therapies warrant current recommendations for a third primary dose in IMID patients treated with immunosuppressive drugs.

SARS-CoV-2 infection and COVID19 vaccination across eight immune-mediated inflammatory disorders: A prospective, real-life Belgian cohort study – the BELCOMID study

“…Subgroup analyses within the TIMT group, revealed anti-TNF and rituximab as risk factors for lower Stiters. This is in line with Garcillàn et al, who found that corticosteroids, B-cell depleting therapies and JAKi substantially affect vaccine immunogenicity (36) and with the VIP-study that revealed lower antibody levels in IBD patients on infliximab with or without thiopurines and tofacitinib (37). Importantly, we confirmed findings from the CLARITY-IBD study, showing that the blunting effect of anti-TNF on S-antibody response is more pronounced than that of the gut-selective vedolizumab (38,39).…”

Higher Cell-Mediated Immune Responses in Patients With Inflammatory Bowel Disease on Anti-TNF Therapy After COVID-19 Vaccination

“…The anti-TNF therapy group was analyzed together regardless of dosing schedule (standard or accelerated) or type of dose (subcutaneous or intravenous), given that previous studies have not shown that they type of therapy impacts vaccine response or if vaccine response was impacted by drug dosing. 18 , 19 ;…”

SARS-CoV-2-Antikörper-Antwort auf die zweite COVID-19-Impfung bei neuromuskulären Patienten unter immunmodulierender Therapie

“…Auch die JAK-Inhibitoren und Antimetaboliten (z. B. Methotrexat [MTX]) wurden ebenfalls mit abgeschwächten Antikörper- und Neutralisationstitern in Verbindung gebracht [ 11 , 19 ]. Allerdings konnte kürzlich für MTX und JAK-Inhibitoren gezeigt werden, dass die dritte Impfdosis zu einem suffizienten Antikörpertiter (> 500 U/ml) bei den meisten Patient*innen führte [ 9 ].…”

“…Allerdings ist im Gegensatz zu den Antikörpertests die Bestimmung der T‑Zell-Antwort aufwendiger (Detektion der antigenspezifischen CD4+- und CD8+-T-Zellen und deren Zytokinausschüttung nach einer entsprechenden In-vitro -Stimulation) und noch nicht hinreichend verbreitet, sodass diese vorzugsweise in den Fällen einer fehlenden humoralen Antwort eingesetzt werden sollte [ 19 ]. Bezüglich der Antikörperbestimmung sollte ebenfalls bedacht werden, dass ein Antikörper-Titer-Cut-off, ab dem ein ausreichender Schutz gegen eine SARS-CoV-2-Infektion angenommen werden kann, bislang nicht definiert ist [ 13 , 25 ].…”