Lower Anti-Vaccine Antibody Levels Observed in Patients With Juvenile Idiopathic Arthritis

Many children with juvenile idiopathic arthritis stop vaccinating when diagnosis is established, despite them being at a greater risk of infections than healthy children due to their aberrant immunity and the use of immunosuppressive drugs.

Patients with juvenile idiopathic arthritis (JIA) were more likely to have lower anti-vaccine antibody levels against vaccines due in part to incomplete vaccination, arthritis, and immunosuppressive drugs like biologics and methotrexate (MTX), according to a study published in Pediatric Rheumatology.1 Investigators urge continued vaccination in this patient population, especially for those with incomplete vaccination and low anti-vaccine antibody levels, as they are deemed safe and effective.

“Patients with JIA are at greater risk of infections than healthy children due to their aberrant immunity and the use of immunosuppressive drugs,” explained investigators. “Vaccinations can decrease the number of infection episodes, maintain treatment of the disease, and restrain remission. However, many children with pediatric rheumatic disease (PRD) stop vaccinating when a diagnosis of rheumatic disease is established… As a result, we have a rather large cohort of immune-compromised children with incomplete vaccination.”

The cross-sectional Russian study analyzed 170 children, aged 2 to 17 years, with JIA who had received routine vaccinations, including measles, rubella, mumps (MMR), diphtheria, and hepatitis B. Patients were divided into 2 categories: complete and incomplete vaccination. Incomplete vaccination was defined as having fewer vaccines or doses to age according to the Russian national vaccine schedule.

Post-vaccination antibodies (IgG) were measured using ELISA. Survival data as well as the continuous, quantitative, and categorial variables were analyzed. The log-rank test compared survival curves in this patient population.

The study found that protective levels of antibodies in this cohort ranged from 50% (against hepatitis B), 52% (diphtheria), 58% (measles), 80% (mumps), and 98% (rubella).

A total of 50 (42%) of patients did not achieve a complete vaccine dosing schedule against MMR. Among patients deemed to have an incomplete MMR vaccination, 39% of patients were being treated with biologics, 22% were treated with MTX, and 14% were using non-steroidal anti-inflammatory drugs (NSAIDs). All patients, however, received all doses against hepatitis B.

When comparing patients with complete and incomplete vaccinations, those with incomplete status had a lower level of antibodies against mumps and diphtheria (p = 0.024). Investigators hypothesized that MTX ([odds ratio] OR = 9.5 [95%CI: 1.004; 90.3]) and biologics (OR = 4.4 [95%CI: 1.6; 12.1]) were strong indicators of diphtheria revaccination omission. Incomplete vaccination was also a risk factor of non-protective levels of antibodies against measles ([hazard ratio] HR = 2.03 [95%CI: 1.02; 4.0], p = 0.042).

Approximately 1 out of 3 patients with JIA continued vaccination, during periods of remission, without incidence of flare or serious adverse events.

Most patients with JIA were without non-protective levels of antibodies, most likely due to the limited number of vaccines they had received. In this study, 100% of young patients received 1 MMR vaccine, and 55.9% (n = 95) received 2 doses. A total of 82 patients (48.3%) received 1-4 doses of the diphtheria vaccine and 88 (51.7%) had received 5-6 vaccines.

Cox proportional regression models confirmed that incomplete vaccination is a risk factor for a non-protective level of antibodies against measles, mumps, and diphtheria. It was also a factor in the severity of arthritis symptoms and immunosuppression. Investigators noted a positive correlation between biologic therapies and incomplete vaccination against MMR and diphtheria. Non-protective levels against measles occurred more in JIA patients with extended MTX treatment (2.8 vs. 2.2 years). Biologic-treated patients were in the lowest probability group of having protective antibodies against diseases such as hepatitis B, mumps, measles, and diphtheria when compared with MTX and NSAIDs.

Investigators theorized that JIA diagnosis, treatment modalities, vaccination coverage, and time since last vaccine injection influenced the level of antibodies against the vaccine.

The study was limited due to the differences in age, onset ages, JIA categories, treatment approaches, disease duration, and an inconsistent time gap between vaccinations. Additionally, the small sample size hinders generalizability.

“Children with JIA have lower antibody levels, and many JIA patients have non-protective levels of antibodies and require a routine check. Individual vaccination schedules are required for JIA patients without protective antibody levels and should be tailored individually with antibody level sampling,” concluded investigators. “It is necessary to decrease the level of apprehension among Russian parents and healthcare providers regarding vaccinations. Further studies on the safety and efficacy of vaccinations in JIA patients are required.”

Reference:

Kostik MM, Lubimova NA, Fridman IV, Goleva OV, Kharit SM. The vaccine coverage and vaccine immunity status and risk factors of non-protective levels of antibodies against vaccines in children with juvenile idiopathic arthritis: cross-sectional Russian tertiary Centre study. Pediatr Rheumatol Online J. 2021;19(1):108. Published 2021 Jul 5. doi:10.1186/s12969-021-00594-2