麻豆传媒

The data thus far for patients with psoriatic arthritis (PsA) who develop COVID-19 suggest that they have similar infection risks and outcomes compared with the wider population -- but with efforts toward vaccination for all and careful modification of immune-suppressing medications during the infection.

However, questions have persisted, particularly because patients with rheumatic autoimmune and inflammatory diseases were not included in the initial COVID vaccine clinical trials.

Vaccine Considerations

Experts agree that vaccination is of utmost importance for patients with PsA during the COVID pandemic. The American College of Rheumatology (ACR) has recommended that all patients with rheumatic autoimmune and inflammatory diseases receive both doses of a primary series, plus a booster, and should be prioritized for vaccination and treatment with monoclonal antibodies or other therapies to mitigate disease.

However, clinicians and patients have raised concerns about vaccination, including the possibility of an inadequate response to the vaccine, breakthrough infections, and the risk of underlying disease flare following vaccination.

"While patients with autoimmune diseases seem to have a lower rate of seroconversion compared with people without autoimmune disorders, the numbers are still relatively high, ranging from 84% to 98%," said Rebecca Haberman, MD, of NYU Langone Health in New York City. Among 165 patients with PsA in a study from Israel, 97% had an adequate antibody response to an mRNA vaccine, she pointed out.

"It is important to remember, however, that we don't know what measurement or level of antibodies mean for clinical immunity -- they are not synonymous. In addition, the vaccine helps other parts of the immune system gear up as well, which cannot be measured by antibodies alone," Haberman told 麻豆传媒.

Antibody response to the vaccine also differs by medication use. "Certain medications, such as steroids, rituximab [Rituxan], methotrexate, and mycophenolate mofetil [Cellcept], have been shown to reduce antibody production to the vaccine," she noted.

In a , researchers reported that there was a 36-fold reduction in humoral responses in patients on B cell-inhibiting therapies and a 13-fold reduction in patients on glucocorticoids. JAK inhibitors and antimetabolites such as methotrexate were also shown to blunt antibody titers, but targeted therapies such as tumor necrosis factor inhibitors and interleukin-12/23 inhibitors had only modest impact on antibody formation and neutralization.

Nonetheless, among patients with rheumatic diseases, including PsA, in a European registry, the vaccine was safe and well tolerated, with severe adverse events being reported in only two out of 1,500 patients. The most common side effects were pain at the injection site, fatigue, and headache. The findings were "very reassuring," the investigators noted.

In , rates of breakthrough COVID-19 infections after vaccination among a national sample of patients with various rheumatic autoimmune or inflammatory diseases were reported in a late-breaking abstract.

Among 47,000 patients with any of these diseases, the rate of breakthrough infection after full vaccination with the Pfizer vaccine was 36 per 1,000 compared with 19 per 1,000 in individuals without rheumatic diseases. For the Moderna vaccine, the rates were 33 versus 16 per 1,000, while for the Johnson & Johnson vaccine, the rates were 47 versus 26 per 1,000.

While breakthrough infections can occur, patients are much less likely to develop severe COVID outcomes, including hospitalization and death, if they have been vaccinated, Haberman emphasized.

She also pointed out that some patients worry about disease flares following vaccination. But "for most, disease activity as measured by standardized instruments remains stable before and after vaccination." Across studies, 5% to 15% of patients have reported flares, with most being mild-to-moderate, she noted.

In , post-vaccination disease flares occurred in 11% of almost 1,400 patients with rheumatic and musculoskeletal diseases, with symptoms of joint pain, stiffness, and swelling in patients with inflammatory arthritis. The flares typically lasted for 10 days, and most often were managed with oral corticosteroids. Risk factors for post-vaccine flare included a history of flare during the previous 6 months and the use of combination therapy. "These factors may be a surrogate for more refractory disease at baseline and thus the relationship with vaccination is unclear," the authors wrote.

Treatment Modifications

The few data available on infection risk in patients with PsA suggest that they have a small increased risk for infection in general, according to Dalit Ashany, MD, of the Hospital for Special Surgery in New York City. "The greater risk of infection is conferred, however, by the immunosuppressive medications used to treat psoriasis and PsA," she said.

The ACR has provided only limited advice on the need for treatment modifications at the time of vaccination for agents used in PsA, suggesting that conventional immunomodulatory or immunosuppressive agents be withheld for 1 to 2 weeks, if disease activity allows, following each vaccine dose.

"But in cases where patients have active or organ-threatening rheumatic disease, continuation of their immunosuppressive therapy may be required based upon an individualized assessment," Ashany noted.

Patients should talk to their caregivers about the risks and whether any adjustments should be made based upon their own disease activity and history, Haberman said. "There is no 'one-size-fits-all' recommendation here," she added.

"We advise our patients who develop COVID-19 infection to hold their immunomodulatory medications, including methotrexate, biologic agents, or other oral agents, but to contact us for personalized recommendations," said John Davis III, MD, of the Mayo Clinic in Rochester, Minnesota. Prednisone should be continued at the same dose, however, he noted.

"Following treatment and recovery from COVID-19, patients should communicate with their rheumatology care team about when to resume their medications," Davis added.

Severe Disease and Mortality

utilizing U.S. Optum COVID electronic health records data found that patients with rheumatoid arthritis (n=2,306) had an increased risk of hospitalization (OR 1.54, 95% CI 1.39-1.70) and in-hospital mortality (OR 1.61, 95% CI 1.30-2.00) compared with a healthy comparator group (n=311,563). Patients with PsA, in contrast, had no increased risks of either hospitalization (OR 0.85, 95% CI 0.65-1.2) or in-hospital death (OR 1.24, 95% CI 0.61-2.55).

Another of patients with autoimmune and chronic inflammatory diseases hospitalized for COVID at five centers in New York City found no overall greater risk for adverse outcomes, including the need for mechanical ventilation and death. The study included 6,792 patients with PCR-confirmed COVID, 2.3% of whom had at least one autoimmune or chronic inflammatory disease. On a multivariable analysis that adjusted for age, sex, race, and comorbidities, no increased risk was observed for patients with these underlying diseases (OR 1.3, 95% CI 0.9-1.8).

In addition, no increased risk was seen for use of conventional immunosuppressive drugs or biologics, but a significantly greater risk was observed for patients on corticosteroids (OR 6.8, 95% CI 2.5-18.4).

More ominous were the of almost 4,000 patients enrolled in the COVID-19 Global Rheumatology Alliance from March to July 2020. The death rate was 10.5%, which was "clearly higher than that reported in the general population in most countries," the researchers pointed out.

Twelve percent of the cohort had PsA. In multivariable analyses, factors that were associated with higher risks of mortality included older age, male sex, smoking, and comorbidities including chronic lung disease and cardiovascular disease.

Risks for mortality were significantly increased among patients receiving daily doses of prednisone above 10 mg (OR 1.69, 95% CI 1.18-2.41).

For adverse outcomes from COVID-19 in general, Haberman advised that "factors such as older age, hypertension, and lung disease, which increase the risk of poor outcomes in the general population, also apply to patients with psoriatic disease."

Finally, according to Davis, "it is prudent for all patients with rheumatic diseases to remain vigilant and follow recommendations for social distancing, masking, and most importantly, get fully vaccinated."

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