Breakthrough studies support new boosters in immunosuppression

Breakthrough studies support new boosters in immunosuppression

People with immune-mediated inflammatory diseases who take immunosuppressants do not have as strong an immune defense against the Omicron variant as against the original wild-type SARS-CoV-2 virus, according to two studies published in Annals of the Rheumatic Diseases. One of the studies further showed that vaccinated individuals taking immunosuppressants had worse cross-neutralizing responses to Omicron than healthy vaccinated individuals, even after three doses of the COVID-19 mRNA vaccines.

“We strongly suggest that if Omicron-specific vaccination can be performed, it may be an effective way to reduce the risk of breakthrough infections in patients with autoimmune rheumatic disease,” said Sang Tae Choi, MD, PhD, of the University College of Medicine in He said in Korean Seoul and one of the authors of the study on protection against cross-neutralization Medscape Medical News. “However, further research is needed on the effectiveness of the Omicron-specific vaccine in patients with immune dysfunctions. We believe that these study results can be of great benefit in determining vaccination strategy in the future.”

An earlier study, published in July, examined the ability of COVID-19 vaccines to induce cross-reactive antibody responses against Omicron infections in patients with autoimmune rheumatic diseases (ARDs). The observational study included 149 ARD patients and 94 healthcare workers as controls, all of whom provided blood samples an average of 15 weeks after the second dose of the COVID vaccine or an average of 8 weeks after the third dose. Slightly more than two-thirds of patients (68.5%) received a third dose of mRNA vaccine. None of the participants had previously had COVID-19.

The researchers compared the rate of breakthrough infections with the Omicron variant to neutralizing responses in the patients’ blood, specifically cross-neutralizing antibody responses, because the original mRNA vaccines targeted a variant other than Omicron. Breakthrough infections were assessed by questionnaire questions.

“Our findings suggest that neither the primary vaccination series nor booster doses are sufficient to induce Omicron-neutralizing responses above threshold in patients with ARDs, although responses were markedly increased after the third dose of mRNA vaccine,” writes Woo-Joong Kim of Chung-Ang University College of Medicine in Seoul, Korea and colleagues. “This disruption of cross-neutralizing reactions in most of our patients contrasts sharply with the strong induction of Omicron-neutralizing reactions after the third vaccination in healthy recipients.”

Average neutralization responses against the original SARS-CoV-2 strain were similar in both groups: 76% in ARD patients and 72% in HCWs after the second dose. The average response after the third dose was 97% in healthcare workers and 88% in patients.

The average cross-neutralizing response against the Omicron variant was much lower, especially in patients with rheumatic disease: only 11.5%, which increased to 27% after the third dose. Only 39% of patient sera showed neutralization of Omicron, even after the third dose. Meanwhile, the average cross-neutralizing response in healthcare workers was 18% after the second dose and 50% after the third.

When researchers compared rates of seropositivity against the original virus with neutralizing responses against Omicron, the association between the two was stronger in healthcare workers than in ARD patients. In fact, among ARD patients who seroconverted, only 41% had any reaction against Omicron. Among all patients, the majority of nonresponders to Omicron (93.5%) initially seroconverted.

The researchers also examined the ability to neutralize Omicron based on disease in those who received three doses of the vaccine. About half of lupus patients (52%) showed any neutralization against Omicron, compared with 25% of rheumatoid arthritis patients, 37.5% of ankylosing spondylitis patients, 33% of Behçet’s syndrome patients, and all those with Still’s syndrome in adulthood. disease.

The rate of breakthrough infections was lower in patients (19%) than in healthcare workers (33%). A similar pattern was observed in a more recent study published on September 5. Researchers used data from a prospective cohort study in the Netherlands to investigate the incidence and severity of breakthrough Omicron infections in patients with immune-mediated inflammatory diseases. The researchers compared infection rates and severity in 1,593 vaccinated patients with inflammatory disease who were taking immunosuppressants and 579 vaccinated controls (418 patients with inflammatory disease not taking immunosuppressants and 161 healthy controls).

One in five patients with inflammatory disease (21%) received immunosuppressants that significantly disrupt antibodies, such as anti-CD20 therapy, S1P modulators, or combination therapy with mycophenolate mofetil, and 48% of these patients seroconverted after primary vaccination compared with 96% of patients. patients taking other immunosuppressants and 98% of controls.

Breakthrough infection rates were similar between the control group (31%) and those taking immunosuppressants (30%). Only three participants had serious illness requiring hospitalization: one control and two patients taking immunosuppressants.

“In both studies, controls had similar or higher rates of breakthrough infections compared to immunosuppressed,” noted Alfred Kim, MD, assistant professor of medicine at Washington University, St. Louis, Missouri, but added, “differences in mitigation strategies such as masking that may explain these findings.” This means that patients taking immunosuppressants may be at fewer risks or have fewer potential exposures in the community, especially in the Korean study where the control groups were healthcare workers.

A larger difference in infections emerged when seroconversion rates were taken into account. The incidence of breakthrough was 38% in those taking immunosuppressants who did not seroconvert, compared with 29% in those who did. A similar trend was observed in the incidence of breakthrough between those taking immunosuppressants strongly damaging antibodies (36% breakthrough rate) and those taking other immunosuppressants (28%).

Among those on immunosuppressants who seroconverted, the primary vaccination series reduced the risk of breakthrough infection by 29%. Protection became stronger with a booster or prior infection, both of which reduced the risk of breakthrough infection by 39% in those on immunosuppressants who seroconverted.

“In patients with immune-mediated inflammatory diseases on immunosuppressants, we demonstrate that additional vaccination is associated with a reduced risk of breakthrough SARS-CoV-2 Omicron infections,” wrote Eileen W. Stalman, MD, PhD, of Amsterdam UMC in the Netherlands, and colleagues.

Although neither study analyzed the immune response or breakthrough infection based on individual drugs, Kim said previous research allows for extrapolation of “previous culprits of poor vaccine responses.” [such as B-cell depleting drugs, mycophenolate, and TNF [tumor necrosis factor] inhibitors will continue to bear the brunt of the breakthrough infection, including Omicron.”

Overall, he found the data from both studies to be relatively consistent with each other.

“Those involved in immunosuppression, particularly mechanisms that have been established as risk factors for poor vaccine response, are at risk for breakthrough infection during the Omicron era,” Kim said.

An earlier study from Korea also found that “the median time between vaccination with the third dose and the date of confirmed breakthrough infection in patients with ARDs was significantly shorter compared to that in healthcare workers”—just 93 days in patients versus 122 days in healthcare workers. They hypothesized that limited Omicron neutralization of this population explained this short-term protection.

The majority of patients with breakthrough infections (74%) in this study showed no neutralization against Omicron, including only two hospitalized patients, both of whom had strong responses to the original SARS-CoV-2 strain. The significant decline over time in neutralization against Omicron suggests “the potential for substantial loss of protection against breakthrough infection,” the authors write.

“Third dose of mRNA vaccine could improve cross-neutralization of SARS-CoV-2 Omicron variant in patients with autoimmune rheumatic disease. [although] more than half of the patients failed to develop omicron-neutralizing antibodies,” said Tae Choi Medscape Medical News. “Our study sheds light on the relative lack of Omicron-specific neutralizing responses in patients with autoimmune rheumatic disease and their presumed vulnerability to breakthrough infection.”

The message for clinicians, Kim said, is to “continue to urge our patients to maintain additional and increasing doses as directed, use pre-exposure prophylaxis such as Evusheld, and continue other mitigation strategies as they have been doing.”

The Dutch study was funded by the Netherlands Organization for Health Research and Development; the Korean study did not use any external funding.

The authors of the Korean study had no disclosures. The authors of the Dutch study cited a wide range of disclosures involving more than a dozen pharmaceutical companies, but did not include Pfizer or Moderna. Among the industry publications of Dr. Kim belongs Alexion, ANI, AstraZeneca, Aurinia, Exagen, Foghorn Therapeutics, GlaxoSmithKline, Kypha and Pfizer .

Ann Rheum Dis. Published online July 25, 2022. Full text

Ann Rheum Dis. Published online September 5, 2022. Full text

Tara Haelle is a health/science journalist based in Dallas. Follow her on @tarahaelle

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