A trio of late-breaking abstracts confirmed earlier findings suggesting that individuals who are immunocompromised are at greater risk for SARS-CoV-2 infection and could gain significant protection from full vaccination. Furthermore, a third dose of an mRNA vaccine can reduce the additional risk of infection in these more vulnerable populations.
The studies were presented during the Late-Breaking Abstracts session on Tuesday, Nov. 9, and can be viewed on demand by registered meeting participants through March 11, 2022.
A retrospective analysis of the National COVID Cohort Collaborative electronic medical record data repository found increased risk of COVID-19 breakthrough infection after vaccination in patients with a variety of autoimmune and inflammatory rheumatic diseases (AIRD) versus a reference group without AIRD or other immunosuppressive conditions, including multiple sclerosis, HIV, malignancies, solid organ transplant, or bone marrow transplant. The analysis included 577,335 patients administered at least one dose of COVID-19 vaccine.
“Patients with rheumatoid arthritis, gout, poly/dermatomyositis, vasculitis, and other rheumatic diseases who are fully vaccinated are at increased risk for breakthrough COVID-19, as are patients on non-biologic disease-modifying antirheumatic drugs (DMARDs), biologics, glucocorticoids, urate-lowering therapy, and other immunosuppressive medications,” said Jasvinder A. Singh, MD, MPH, Professor of Medicine and Epidemiology and the Musculoskeletal Outcomes Research Endowed Professor of Medicine at the University of Alabama at Birmingham. “The data support FDA recommendations for a third dose of mRNA vaccine for patients who are immunosuppressed or compromised, including those with autoimmune or inflammatory rheumatic diseases who are getting medications associated with immunosuppression.”
A second retrospective study found that a third dose of an mRNA COVID-19 vaccine increased antibody production and enhanced cellular immune response, even in immunosuppressed patients who showed minimal response to the first two doses of an mRNA vaccine. The study also found that rituximab reduces vaccine response.
Rituximab eliminates peripheral B cells, noted Michael Bonelli, MD, Associate Professor of Rheumatology at the Medical University of Vienna, Austria. Not surprisingly, patients on rituximab have higher rates and longer duration of hospitalization for COVID-19, more severe disease, and higher mortality compared to patients on TNF-inhibitors, he said.
In the study, a cohort of 74 rituximab patients had a reduced humoral immune response to COVID-19 vaccination versus healthy controls, 39% to 100%, respectively. Peripheral B cells predicted seroconversion, while age, conventional DMARDs, and glucocorticoid use did not.
Rituximab patients also showed a reduced T-cell response in the study, while nearly a third of rituximab patients, 31%, showed neither humoral nor cellular immune response to vaccination, Dr. Bonelli said. After an mRNA booster, only 6% of rituximab patients still had no vaccine response.
“We recommend mRNA booster vaccine for all immunocompromised patients,” Dr. Bonelli said. “And for patients who are clinically stable, we recommend delay in rituximab until after initial vaccination and booster.”
The final COVID-19 late-breaking study examined vaccine immunogenicity in patients on therapeutic immunosuppression. Interim results from the prospective study of 82 patients in the United Kingdom showed that methotrexate — but not biologics targeting TNF, IL-17, and IL-23 — impaired humoral immunity to a first dose of COVID-19 vaccine BNT162b2 (Pfizer-BioNTech), but not cellular response.
Following a second vaccine dose, all patients on immunosuppression showed seroconversion with anti-spike IgG titers similar to controls, reported Satveer Mahil, MD, Consultant Dermatologist and Senior Lecturer at St. John’s Institute of Dermatology, King’s College, London, United Kingdom. Neutralization activity against wild-type SARS-CoV-2, the alpha variant, and the now-predominant delta variant were similar whether patients were on methotrexate or biologics for therapeutic immunosuppression.
Cellular immunity rates were lower in the immunosuppressed group, 71%, versus 100% in the control group (p=0.02).
“These results support the prioritization of immunocompromised patients to receive a further dose of vaccine,” Dr. Mahil said.
Secukinumab safe, effective in giant cell arteritis
The first large-scale trial of secukinumab in giant cell arteritis (GCA) showed greater sustained remission versus placebo and longer time to first flare with no unexpected safety signals, reported Jens Thiel, MD, from the Division of Rheumatology and Immunology at Medical University of Graz, Austria. Secukinumab has been approved by the U.S. Food and Drug Administration (FDA) for plaque psoriasis and other IL-17A-driven diseases, but has not been widely studied in GCA.
In the TitAIN phase II study, which is the largest trial of secukinumab in GCA to date, 52 patients were randomized to secukinumab (n=27) or placebo (n=25) for 52 weeks. The primary endpoint was sustained remission of GCA at week 28. Secondary endpoints included clinical status at week 52 and safety.
“Patients on secukinumab were 9.3 times more likely to remain in remission through week 28 versus controls,” Dr. Thiel said. “At week 52, 59.3% of secukinumab patients had sustained remissions versus only 8% of placebo patients. The mean time to first flare for placebo was 197 days, but we did not reach the mean time in the secukinumab group because there were so few events. A phase 3 study has just started and enrolled the first patient.”
Emapalumab effective in MAS in sJIA
Patients with systemic juvenile idiopathic arthritis (sJIA) complicated by macrophage activation syndrome (MAS) may benefit from emapalumab, an anti-IFNγ antibody, according to Fabrizio De Benedetti, MD, PhD, Chief of Rheumatology at Ospedale Pediatrico Bambino Gesù in Rome, Italy.
Pathologic over-production of IFNγ is seen in several animal models of hemophagocytic lymphohistiocytosis (HLH) and MAS, noted Dr. De Benedetti. Emapalumab has been approved by the FDA for HLH, and overexpression of IFNγ is present in human MAS.
A single-arm, open-label study of emapalumab in 14 sJIA patients who did not respond to high-dose glucocorticoids or other treatments showed 11 patients in MAS remission at week 8. One patient stopped treatment early after an investigator’s assessment of MAS remission, and two patients had MAS remission at week 4 but not at week 8. The median dose of glucocorticoids fell from 15.7 mg/kg during week 1 to 0.56 mg/kg during week 8.
“These results demonstrate the pathologic role of IFNγ in MAS and the value of IFNγ neutralization in patients who have failed steroid treatment. The data point to IFNγ neutralization as the standard of care in MAS,” Dr. De Benedetti said.
Rituximab for eosinophilic granulomatosis with polyangiitis
The first head-to-head trial of rituximab versus cyclosporin plus glucocorticoids for the induction of remission of eosinophilic granulomatosis with polyangiitis (EGPA) showed similar results to a French study examining the two approaches. A U.S.-based consensus panel has suggested consideration of both cyclosporin and rituximab to induce remission in active severe EGPA, while French recommendations call for cyclosporin plus glucocorticoids.
The French REOVAS trial randomized 52 EGPA patients to rituximab and 53 to cyclosporin plus glucocorticoids. The primary outcome was EGPA remission and glucocorticoid use ≤7.5 mg/day at day 180.
“Complete remission was comparable between the two groups or for relapse-free survival at day 180,” reported Benjamin Terrier, MD, PhD, Professor of Medicine at Cochin Hospital in Paris, France. “Prednisolone use was also similar — 4,591 mg/day in the rituximab group and 4,453 mg/day in the conventional treatment group. There was no difference in quality of life and similar adverse events. Rituximab was not superior to the conventional strategy, but is an option, especially for young females with reproductive concerns.”