Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic review and meta-analysis

Abstract

Objectives The treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic review about seroconversion after SARS-CoV-2 vaccination in patients with IMIDs and impact of various drugs on seroconversion rates. Methods Electronic databases were searched to identify relevant studies reporting seroconversion rates following SARS-CoV-2 vaccination in IMIDs. We calculated the pooled seroconversion rates after a single or two doses of vaccination, pooled seroconversion rates in patients with specific IMIDs, and rates in patients on various drugs/drug classes. Results Twenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9–89.0, I 2 = 90%) as compared to a single dose (69.3, 52.4–82.3, I 2 = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02–0.13, I 2 = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6–96.9, I 2 = 0%), spondyloarthropathy (95.6, 95% CI: 83.4–98.9, I 2 = 35%), and systemic lupus erythematosus (90.7, 95%CI: 85.4–94.2, I 2 = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1–88.9, I 2 = 85%), and vasculitis (70.5, 95% CI: 52.9–83.5, I 2 = 51%). The seroconversion rates following double dose of mRNA were excellent (>90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (<70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70–90%) with steroids, hydroxychloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immunomodulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy. Conclusion Seroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain therapies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.

Evaluation of antibody response to BNT162b2 mRNA COVID-19 vaccine in patients affected by immune-mediated inflammatory diseases up to 5 months after vaccination

“…In contrast, the available studies to date show that a full course of mRNA vaccine in patients with IMID elicit a response in 78-100% of subjects [21], showing reduced serum antibody IgG titers and serum neutralizing activity as compared to healthy controls [10,13,14,[22][23][24]. Reduced humoral and cellular immune response (CD8 +) to COVID-19 mRNA vaccines were found by Haberman et al in IMID treated with methotrexate and by Mahil et al in psoriasis (47% and 62% responders, respectively) [23,25], although this finding has not been confirmed in our and other studies (> 80% responders) [14,21,22,26]. Some factors such as the characteristics of enrolled populations and selection criteria may explain this difference.…”

“…Initial immunogenicity data available for at-risk subgroups showed a high proportion of non-responders and low antibody responses to the SARS-CoV-2 spike protein in patients who received solid-organ transplantation [18], patients treated for solid cancer [19], or in patients with ongoing hemodialysis [20]. In contrast, the available studies to date show that a full course of mRNA vaccine in patients with IMID elicit a response in 78-100% of subjects [21], showing reduced serum antibody IgG titers and serum neutralizing activity as compared to healthy controls [10,13,14,[22][23][24]. Reduced humoral and cellular immune response (CD8 +) to COVID-19 mRNA vaccines were found by Haberman et al in IMID treated with methotrexate and by Mahil et al in psoriasis (47% and 62% responders, respectively) [23,25], although this finding has not been confirmed in our and other studies (> 80% responders) [14,21,22,26].…”

Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis: a prospective, cohort study

“…Observational data in small cohorts of patients with rheumatoid arthritis have indicated that rituximab impairs serological SARS-CoV-2 vaccine responses. 8 , 9 , 10 , 11 Previous reports have suggested that T cells are necessary for protection against severe COVID-19 in settings of low antibody titres, 12 for rapid and efficient resolution of COVID-19 13 and for protection against fatal outcomes in patients treated with anti-CD20 therapies for haematological malignancies. 14 To date, sparse data exist regarding cellular responses to SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis.…”

Attenuated anti-SARS-CoV-2 antibody response to vaccination in patients with rheumatic diseases

“…In recent studies, certain therapies (anti-TNF, anti-IL17, anti-IL6, anti-IL12/23) seem not to impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses in patients treated with immunosupressors for different rheumatic and non-rheumatic diseases ( 2 , 5 ). Furthermore, we confirm a good response to vaccination in patients treated with TNF blockers, anti-IL 17, anti-IL6, anti-12/23 therapies and observed a poor response in patients treated with anti-CD20/anti-CTLA-4 although numbers are low (n=5).…”

“…Furthermore, we confirm a good response to vaccination in patients treated with TNF blockers, anti-IL 17, anti-IL6, anti-12/23 therapies and observed a poor response in patients treated with anti-CD20/anti-CTLA-4 although numbers are low (n=5). Conflicting results were reported in patients using methotrexate ( 5 , 6 ). We did not found that methotrexate hampers humoral response to vaccine in our cohort.…”