RA TNF Antagonists
Abstract 1235: Abilities to Develop Protective Antibodies to Pneumococcal and Influenza Vaccine are Maintained in Rheumatoid Arthritis (RA) Patients Treated with Adalimumab (Humira®)
TNF inhibitors, by way of direct inhibition of TNF-α and via suppression of down-stream cytokine production and subsequent immune effector cell function, have the potential to blunt protective acquired humoral immune responses to vaccination. The small amount of investigation in this area has suggested that vaccine responses may be diminished in RA patients (in general) and particularly in those receiving biologic DMARD therapies, although on average responses do not appear to result in levels that would not be sufficient to adequately suppress infection. Here, Kaine et al. investigate vaccine responses to influenza and pneumococal vaccination in RA patients treated with the TNF inhibitor, adalimumab.
Methods Subjects were enrolled just prior to the 2003-2004 influenza season to receive adalimumab (80 mg on day 1 and 40 mg every two weeks thereafter) vs. placebo in addition to background non-biologic DMARDs in a randomized, double-blind fashion. Subjects who had received influenza vaccination in the prior 6 months or pneumococcal vaccination in the prior 5 years were not included. Standard polyvalent pneumococcal and inactivated trivalent influenza vaccine (H1N1, H3N2, and Hong Kong) were administered on day 8. Vaccine responses were measured on days 8 and 36 with protective antibody level and response to vaccination predefined for pneumococcal and influenza vaccines.
Results 208 of the 226 randomized subjects had complete data. Baseline demographics were typical for RA therapeutic trials and were balanced between the adalimumab and placebo groups. There was no difference in RA therapeutics or CRP between groups.
At baseline, 57.7% of the placebo treated subjects compared to 58.6% of the adalimumab treated subjects had protective antibodies against influenza. After vaccination, 63.3% of placebo treated subjects vs. 51.5% of adalimumab treated subjects demonstrated an appropriate rise in antibody titer after influenza vaccination, with 94.5% of placebo treated subjects vs. 98% of adalimumab treated subjects demonstrating protective antibody status on follow-up at 36 days.
At baseline, 56.8% of placebo treated subjects vs. 57.6% of adalimumab treated subjects had protective antibodies to pneumococcus. After vaccination, 40.4% of the placebo treated subjects vs. 37.4% of the adalimumab treated subjects demonstrated an appropriate rise in antibody titer after pneumococcal vaccination, with 81.7% of the placebo treated subjects vs. 85.9% of the adalimumab treated subjects demonstrating protective antibody status on follow-up at 36 days.
Conclusions The ability to develop protective humoral immunity responses against influenza and pneumococcal vaccination was not impaired by adalimumab therapy at initiation of therapy.
Editorial Comment This is a well designed and adequately powered study that can be considered definitive for the questions that it poses. The results are reassuring, particularly for the near complete levels of protective immunity achieved in the RA patients, in general. Some issues apply for clinical practice. First, the subjects were vaccinated very early in therapy with adalimumab, before steady-state levels of adalimumab (even with the loading dose used) can be expected. Since influenza vaccination, in particular, is not available all year it is often impossible to administer influenza vaccine at the initiation of therapy. This study, as definitive as it is, cannot address whether the same responses would be seen if vaccination occurred later in the treatment course. Second, TNF inhibitor therapy may promote a more rapid waning of protective humoral immunity over time in those who initially demonstrated protective antibody levels, resulting in the need for more frequent repeat immunization with “booster” shots. These issues would require different study methods than the one used here to be adequately evaluated.
