Opsonic and Antibody Responses to Pneumococcal Polysaccharide in Rheumatoid Arthritis Patients Receiving Golimumab Plus Methotrexate.

Vaccination against Streptococcus pneumoniae is recommended for rheumatoid arthritis (RA) patients receiving immunosuppressive treatments. The objective of this study was to evaluate the humoral response to 23-valent pneumococcal polysaccharide vaccination (PPSV23) in RA patients receiving methotrexate (MTX) alone or in combination with a tumor necrosis factor inhibitor, golimumab (GOM).PPSV23 was given to 114 RA patients, who were classified into three groups: RA control (n = 35), MTX alone (n = 55), and GOM + MTX (n = 24). Before and 4 to 6 weeks after vaccination, concentrations of antibodies against pneumococcal serotypes 6B and 23F were measured using an enzyme-linked immunosorbent assay and antibody functionality was determined using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI).The IgG concentrations and OIs were both significantly increased in all treatment groups in response to PPSV23 vaccination. In the GOM + MTX group, the IgG responses were lower than those in the MTX alone or control groups, whereas the OI responses were similar to those in the other 2 groups. Furthermore, discrepancies between the IgG and OI responses were found in GOM + MTX group. No severe adverse effect was observed in any treatment groups.OI responses indicate that antibody functionality rather than antibody quantity is important. The similarity of these measurements between all 3 groups suggests that RA patients receiving MTX + GOM still benefit from receiving the PPSV23 vaccination, even though they produce less IgG in response to it. These results can help clinicians to better schedule and evaluate pneumococcal vaccination for RA patients.

Post-approval appending of CSARs to drug package inserts: an analysis of the types of adverse reactions and time to addition.

PURPOSE: The aim of this study was to quantitatively analyze clinically significant adverse reactions (CSARs) added to drug package inserts after approval and to investigate the time to these post-approval additions as an indicator of safety-related regulatory actions. METHODS: Drugs containing new active ingredients that had been approved in Japan from April 2001 to December 2010 were analyzed. We examined CSARs that had been reported in the first version of the package inserts and subsequent additions through notifications from Japan's Ministry of Health, Labour and Welfare until the end of 2011. Relative risks (RRs) for post-approval addition of CSARs were calculated for various categories of disorders. The median lengths of time to post-approval addition of CSARs were compared. RESULTS: A total of 238 drugs were examined. Of the 2487 CSARs associated with these drugs, 737 had been added after approval. The analysis revealed a higher likelihood for post-approval addition of CSARs for "Hepatobiliary disorders" (RR: 1.41; 95% confidence interval [CI]: 1.19-1.68), "Gastrointestinal disorders" (RR: 1.35; 95%CI: 1.10-1.66), and "Musculoskeletal and connective tissue disorders" (RR: 1.52; 95%CI: 1.11-2.07). In contrast, "Cardiac disorders" showed reduced likelihood in comparison with other disorders. For the time until post-approval addition of CSARs, "Skin and subcutaneous tissue disorders" showed the longest durations, with a median of 3020 days. CONCLUSIONS: Our quantitative analysis suggests that some CSARs were added more frequently to package inserts after approval and that time to post-approval additions of CSARs varied with the types of adverse drug reactions. These results can support the coherent implementation of pharmacovigilance activities.