Prime-Boost Bests a Single Pneumococcal Vaccination in Patients Receiving DMARDs

Prime-boost vaccination is more immunogenic than single pneumococcal vaccine in conventional disease-modifying antirheumatic drug (cDMARD) or abatacept-treated patients, but not in patients on rituximab, say researchers writing in Arthritis Research & Therapy.

Pneumonia is an important cause of the excess mortality in patients with rheumatoid arthritis. While invasive pneumococcal disease, caused by Streptococcus pneumoniae, is a vaccine-preventable life-threatening condition, the 2018 incidence rate was reported to be 65/100,000 person years in patients with chronic inflammatory disease, compared to 10/100,000 in healthy people.

Two pneumococcal vaccines are available for immunization of adults, the 23-valent pneumococcal polysaccharide (PPV23) and the 13-valent conjugate vaccine (PCV13). The Centers for Disease Control and Prevention recommends that adults with immunocompromising conditions receive immunization with a dose of PCV13, followed after at least eight weeks by a dose of PPV23, because of the wider serotype coverage. This prime-boost pneumococcal vaccination strategy is also recommended by the European Society of Clinical Microbiology and Infectious Diseases. While the European League Against Rheumatism recommends pneumococcal vaccination in adults with autoimmune inflammatory rheumatic disease, it does not provide specific guidance due to the lack of evidence on the efficacy, immunogenicity, and safety of available vaccines.

“Whether the prime-boost strategy has advantages over single-dose PCV13 or PPV23 in patients with inflammatory rheumatic diseases, and in the context of different immunosuppressive treatments are still not fully understood,” wrote the authors, led by Per Nived, M.D., of Lund University in Sweden.

In the study, patients receiving rituximab (n = 30), abatacept (n = 23), monotherapy with cDMARDs (methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls (n = 28) were immunized with a pneumococcal conjugate vaccine (PCV) dose followed by PPV23 after eight weeks or more. Specific antibodies to 12 serotypes included in both vaccines were determined from blood samples before and four to eight weeks after each vaccination.

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Compared to single-dose PCV, prime-boost vaccination increased the number of serotypes with positive antibody response (≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration) in patients on abatacept, cDMARDs, and controls (p = 0.02, p = 0.01, and p = 0.01), but not in those on rituximab.

The authors write that while previous studies have shown reduced immunogenicity of either single-dose PPV23 or PCV13 in rheumatoid arthritis patients with rituximab, “we observed no improvement of IgG response or opsonophagocytosis with prime-boost vaccination compared to PCV during rituximab treatment.”

After prime-boost vaccination, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared to controls but lowest in rituximab, followed by the abatacept and cDMARD group (p < 0.001). Compared to PCV alone, the number of serotypes with putative protective levels (IgG ≥ 1.3 μg/mL) after prime-boost vaccination increased significantly only in patients in cDMARDs (p = 0.03) and controls (p = 0.001). Rituximab treatment was associated with large reduction (coefficient − 8.6, p < 0.001) and abatacept or cDMARD with moderate reductions (coefficients − 1.9 and − 1.8, p = 0.005, and p < 0.001) in the number of serotypes with positive antibody response to prime-boost vaccination.

Opsonophagocytic activity (serotypes 6B and 23F) was reduced in rituximab (Pn6B and Pn23F, p < 0.001), abatacept (Pn23F, p = 0.02), and cDMARD groups (Pn6B, p = 0.02) compared with controls.

“Prime-boost vaccination strategy might be more beneficial compared to a single vaccine dose in patients treated with conventional DMARDs (i.e., methotrexate, azathioprine, or mycophenolate mofetil) and also in patients receiving abatacept,” wrote the authors.

“Compared to single vaccine, prime-boost pneumococcal vaccination strategy is not more immunogenic in rituximab-treated patients,” the authors wrote. “Pneumococcal vaccination should ideally be performed prior to initiation of rituximab treatment.”

REFERENCE

I Per Nived, Göran Jönsson, Bo Settergren, et al. “Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients.”Arthritis Research & Therapy. February 22, 2020. DOI: https://doi.org/10.1186/s13075-020-2124-3