- Rheumatologic diseases and the medications given for them may disrupt immune function and thereby alter vaccine effectiveness.
- Systemic sclerosis (SSc) has not been well studied in this regard, so researchers in Brazil conducted a secondary analysis of a prospective trial with the recombinant herpes zoster vaccine in SSc patients and healthy controls.
- Serological responses were weaker in patients versus controls, as were injection-site reactions; no worsening of SSc was observed.
Brazilian patients with systemic sclerosis (SSc) had a lower immune response to the recombinant herpes zoster vaccine (Shingrix) compared with healthy controls in a randomized trial, casting doubt on the vaccine’s long-term effectiveness in this population.
With 68 SSc patients and 299 controls receiving the two-dose vaccination on schedule, seroconversion was documented in 92.6% of patients versus 99.7% of controls (P<0.001), with conversion defined as at least four-fold increase in anti-glycoprotein E antibodies, according to Eloisa Bonfá, MD, PhD, of the Universidade de Sao Paulo in Brazil, and colleagues.
And those figures may overstate the vaccine’s effectiveness in SSc patients. Geometric mean concentrations and factor increases in patients were only about half of those seen in controls, the group reported in Rheumatology:
- Geometric mean concentration: 5.81 in patients, 12.6 in controls (P<0.001)
- Factor increase: 31.0 in patients, 59.4 in controls (P<0.001)
But the researchers also indicated that adverse effects were no worse in the patients — including no increase in SSc flares or patient-reported symptoms — and cell-mediated immunity was not significantly reduced relative to controls.
Overall, they wrote, the findings showed that “the magnitude of antibody response was significantly reduced compared to health controls, raising concerns about long-term protection.” But that doesn’t mean SSc patients shouldn’t get the vaccine; on the contrary, because the vaccine appeared to pose no safety risks, the results “support the integration of RZV [recombinant zoster vaccine] into prevention strategies for SSc patients, while highlighting the need for long-term studies on durability of protection,” Bonfá and colleagues concluded.
Vaccine effectiveness is a concern with all rheumatologic diseases. These conditions, almost by definition, involve immune system disruption, and patients are typically treated with medications that cause further immune alterations. Many vaccine effectiveness studies have been conducted in the context of autoimmune disease, but not many involving SSc and the shingles vaccine. Bonfá and colleagues noted that none have examined the product’s potential effects on SSc disease activity.
The current study was actually a secondary analysis of a trial in which the recombinant vaccine was tested in more than 1,000 patients with a variety of autoimmune diseases as well as healthy controls. This new analysis focused on SSc patients who were receiving standard immunosuppressants such as mycophenolate mofetil (but excluding rituximab and cyclophosphamide). In this trial, autoimmune disease patients were randomized to the active vaccine (two doses as the label recommends) or placebo, and then after some time had elapsed, the placebo group received the vaccine. Responses were measured in both groups after they had completed the active vaccine schedule.
Patients differed considerably from controls in age and especially race-ethnicity. Mean age for patients was 53 versus 55 among controls, and 44% of patients were Black as opposed to 19% of controls.
Some 59% of patients were taking mycophenolate and 30% were on methotrexate. Other medications included leflunomide (11%), prednisone (15%), azathioprine (4%), and tocilizumab (Actemra, 4%).
Somewhat surprisingly, seroconversion rates for patients did not differ among the different types of SSc medication, nor for demographic or clinical factors.
Cell-mediated immunity, as indicated by glycoprotein E-specific T-cell counts, was analyzed in about 10% of participants, showing no important difference between patients and controls.
Local reactions were less marked in patients versus controls, while systemic reactions occurred in about 60% of both groups. Some adverse reactions were, however, more common in patients: dyspnea (9.2% vs 0.3%), tremor (6.6% vs 1.3%), and vomiting (5.3% vs 1.0%); some of these may have stemmed from the disease rather than the vaccination.
In the initial phase of the trial, when half the SSc patients got the vaccine and the rest placebo, no difference was seen in disease-related outcomes. These groups experienced flares at the same rate and patient-reported outcomes didn’t differ, either.
