Impact of Biological Therapies on the Immune Response after Pneumococcal Vaccination in Patients with Autoimmune Inflammatory Diseases.

Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol.

Serological response to influenza vaccine in patients with autoimmune inflammatory diseases: Results of RIER study. / Respuesta serológica en pacientes con enfermedades inflamatorias autoinmunes tras la vacunación de la gripe: resultados del estudio RIER.

BACKGROUND: Influenza vaccine is recommended for patients with autoimmune inflammatory diseases (AIID) on biological therapy. OBJECTIVE: To evaluate whether serological response to Influenza vaccine obtained in patients on biological therapy is similar to that achieved in patients on synthetic disease-modifying anti-rheumatic drugs (DMARDs) and that obtained in healthy controls. METHODS: We designed a cohort study in which patients with AIID, 68 on biological therapy and 46 on synthetic DMARDs, as well as 48 healthy controls, were included and vaccinated during the 2015-2016 influenza season. ELISA was used to measure Influenza antigen (Ag) A and B antibodies, before and after vaccination. RESULTS: After vaccination, 88.24% of patients on biologics, 71.74% of those on synthetic DMARDs and 89.58% of healthy controls, presented detectable antibodies against antigen A, while 42.65% of subjects on biologics, 41.30% of those on DMARDs and 54.17% of healthy subjects were seropositive against Ag B. We did not find statistical differences. CONCLUSIONS: In our study, biological therapy is not associated with worse serological response.

Evaluation of the immune response to hepatitis B vaccine in patients on biological therapy: results of the RIER cohort study.

To evaluate the response to hepatitis B virus (HBV) vaccine in patients on biological therapy. Adults with autoimmune inflammatory diseases on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included. Hepatitis B surface antibody (anti-HBs) was measured by ELISA before and after vaccination. Seroconversion was considered when an anti-HBs titer > 10 mIU/mL was achieved. The effect of treatment on the immunoprotective state was studied. The response was compared with that obtained in patients on synthetic disease modifying anti-rheumatic drugs (DMARDs) and healthy controls. A total of 187 patients on biologicals, 48 on synthetic DMARDs, and 49 on healthy controls were analyzed. More than 80% of patients on biologics responded to the vaccine but required more boosters and second vaccine series. Patients who achieved seroconversion were younger than those who did not (47.10 ± 12.99 vs. 53.18 ± 10.54 years, p = 0.012). Being on etanercept or golimumab was associated with seroconversion, while being on rituximab was not. Seroconversion was achieved in 93.75% of patients on synthetic DMARDs and 97.96% of healthy controls. The seroconversion rate in the biologics group was lower than in the synthetic DMARD group (p = 0.043) and tended to be lower than in the healthy group (p = 0.056). In patients on biological therapy, a high rate of HBV vaccine response can be achieved when a complete vaccination schedule is administered. Vaccination while not on biological agents reduces the requirement for boosters and revaccination. Key points: • Patients on biological therapy can achieve high rates of immune response to HBV vaccine when complete vaccination schedules are administered. • However, to achieve such a high seroconversion rate, more boosters and second vaccination series are required. • This supports the proposal already made to provide HBV vaccination to all patients with an autoimmune inflammatory disease after the diagnosis is made and not when the use of a biological treatment is under consideration.

Secukinumab does not impair the immunogenic response to the influenza vaccine in patients.

Objective: To evaluate whether immunological response to influenza vaccination is impaired in patients who are receiving secukinumab. Patients and methods: Subjects suffering from psoriatic arthritis or ankylosing spondylitis who were receiving treatment with secukinumab and healthy volunteers were included.All participants received seasonal inactivated trivalent influenza vaccine recommended by the WHO in the 2017-2018 northern hemisphere influenza season, which contained an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus and a B/Brisbane/60/2008-like virus.Haemagglutination inhibition was used to evaluate basal antibody (Ab) titres against the three influenza vaccine virus strains just before vaccination and at least 4 weeks after the vaccine administration. Response to vaccine was considered as >4-fold increases in Ab titre. Results: Thirty subjects, 17 patients and 13 healthy controls, with a follow-up duration of 33±8 days, were analysed. There were no demographic differences between groups. Patients and controls achieved a median of 4.6-fold and 4.0-fold increases, respectively, for anti H1N1 and almost 4.0 (3.7) for patients and 5.3 for controls for anti-B Ab. Both groups presented a poor response against H3N2, with <1.5-fold increase. Seroconversion rates were similar in both groups. Secukinumab did not influence the response to the influenza vaccine (relative risk: 1.09 (95% CI 0.58 to 2.07) for H1N1, RR: 1.53 (95% CI 0.15 to 15.0) for H3N2 and RR: 0.72 (95% CI 0.32 to 1.83) for B strain). Conclusion: In our study, secukinumab has no effect on the immunogenic response to the influenza vaccine.

Antibody responses to influenza vaccine in patients on biological therapy: Results of RIER cohort study.

BACKGROUND AND OBJECTIVES: Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. MATERIAL AND METHODS: Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. RESULTS: 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054). CONCLUSIONS: Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule.