Assessing Vaccine Safety for Young People With Rheumatic Disorders
Areas of the most concern involved variations in recommended dosing of steroid therapies for autoimmune rheumatic diseases and in the recommended intervals between vaccines for these patients.
Risk for infection is a constant concern in children and adolescents with autoimmune rheumatic diseases (ARDs), and although many infectious diseases are frequently preventable by vaccines, the issues with vaccine administration in young patients with ARD are many.
First, vaccine efficacy is often limited in the presence of immunodeficiency, as well as by the therapies used to manage ARDs, as the immunosuppressant activity to antirheumatic drugs significantly works against the activity of the vaccine. The degree of immunosuppression caused by antirheumatic drugs is largely unknown, and it has also not been established how long antibodies remain present after vaccination, information that is necessary to determine optimal dosing and scheduling of boosters.
A 2014 comparison by Papadopoulou and Sipsas1 of national vaccine recommendations for adult patients with ARDs in Europe, North America, and Australia found significant differences between individual guidelines for 21 countries, "reflecting the lack of evidence-based data," the authors wrote.1 Areas of the most concern involved variations in recommended dosing of steroid therapies for ARDs, as well as in the recommended intervals between vaccines for these patients.1
The effect of rheumatic disease on vaccine efficacy has not been directly studied in children. A 2017 systematic review by Sousa and colleagues2 of 28 studies of children and adolescents found that all studies used seroprotection or seroconversion rates as markers of efficacy. By these measures, 82% of patients achieved adequate seroprotection, although antibody rates generated in the ARD population were significantly lower than among healthy controls given the same vaccines.
Another factor is that the safety of vaccines in this population is not well proven. Often, concerns over the potential for vaccines to trigger exacerbations to rheumatic conditions cause physicians to avoid vaccinating patients with these diseases. At least, in the case of the most common community-transmitted diseases (pneumococcus and influenza), it appears the risk for these diseases overshadows the risks posed by the vaccines.
A recent investigation by Lopez et al3 evaluated 12 sets of international guidelines on various high-risk patient groups, of which 6 guidelines addressed patients (adults only) with rheumatic diseases. The overall conclusions were that the pneumococcal pneumonia and seasonal injectable influenza are the 2 essential vaccines that are recommended for all immunocompromised patients, with the caveat that live vaccines are generally contraindicated in patients with any immunity disorder.3
Overall, vaccines in pediatric patients with ARDs achieved good immunization in all studies. A task force of the European League Against Rheumatism (EULAR) conducted a systematic review of abstracts from the 2008-2009 annual meetings of EULAR and the American College of Rheumatology.4 Most reviewed vaccines for seasonal influenza (n=41) or pneumococcal (n=23) pneumonia, and 26 studies were in pediatric patients.
The EULAR task force found that overall, vaccine recommendations for children and adolescents with rheumatic diseases follow the recommendations for immunosuppressed patients, in whom live-attenuated vaccines are contraindicated when using high-dose immunosuppressive drugs.5,6 The group achieved 92% consensus on multiple recommendations.
The most important finding of the EULAR task force was the determination that the seasonal influenza vaccination was both safe and immunogenic in adult and pediatric patients with ARD. The safety of the live attenuated vaccine is not well established, and the EULAR group reported that, "more studies are required before recommendations on primary vaccinations with live-attenuated vaccines can be made." Given these limitations, the group recommended that pediatric patients who are immunosuppressed can receive annual influenza vaccinations, but they should be administered vaccines containing only inactivated virus.