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Outpatient COVID-19 treatment with monoclonal antibodies or antiretroviral medications such as nirmatrelvir-ritonavir (Paxlovid) administered to patients with systemic autoimmune rheumatic disease led to lower odds of having severe outcomes when compared with similar patients who received no outpatient treatment in a real-world, retrospective analysis of cases.
Investigators found that there were nine hospitalizations or deaths (2.1%) among 426 patients who received outpatient treatment compared with 49 (17.6%) among 278 who did not receive outpatient treatment, yielding an odds ratio of 0.12 (95% confidence interval, 0.05 – 0.25), after adjusting for age, sex, race, comorbidities, and kidney function. The study was published in Lancet Rheumatology.
“Across the board, there was a really strong association with receiving outpatient treatment and lower risk of severe COVID-19,” senior author Jeffrey A. Sparks MD, MMSc, assistant professor of medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts, told Medscape Medical News. “It is pretty powerful evidence that in this high-risk group, that treatment still matters related to preventing severe COVID. We found almost all patients who had severe COVID-19, either hospitalized or who had died, were in the untreated group.”
Early Outpatient Treatment an Important Tool in Patients With Rheumatic Disease
Sparks noted that he and coinvestigators conducted the study because the benefit of outpatient COVID-19 treatments in individuals with systemic autoimmune rheumatic disease was not adequately determined in clinical trials because they had infrequent enrollment of such patients.
The analysis included 704 patients with a mean age of 58.4 years who were seen at Mass General Brigham Integrated Health Care System, a multicenter healthcare system that includes 14 hospitals and primary care or specialty outpatient centers in the Boston, Massachusetts, area. A majority were female (76%) and White (84%). Nearly half had rheumatoid arthritis. Of the 704, 426 (61%) received outpatient treatment, which included nirmatrelvir-ritonavir (n = 307), monoclonal antibodies (n = 105), molnupiravir (n = 5), remdesivir (n = 3), and combination treatment (n = 6).
The findings underline the need to individualize approaches to outpatient treatment in those who test positive for SARS-CoV-2 to fend off severe COVID-19, according to Sparks. “It seems if you are vaccinated and in the general population that you are way less likely to have severe COVID-19 in the current environment, but that doesn’t necessarily apply to some high-risk groups like patients on immunosuppression,” he said. “There are still patients at risk of severe COVID-19, and some of them are in this group of rheumatic patients. This should be part of the discussion related to deciding whether or not to treat.”
Sparks noted that vaccination against COVID-19 confers protection against developing severe COVID-19 in patients with rheumatic disease as it does in the general population, but patients with rheumatic diseases remain at increased risk for severe presentation. “Certainly, the vaccines really help our patients too, but there’s still a bit of a gap between the risk for our patients with rheumatic diseases and the general population” in developing severe COVID-19, he said.
Sparks said he hopes the results represent a “call to action” that even among vaccinated patients there are still some who have poor outcomes, and that early outpatient treatment appears to be an important tool in the fight against poor outcomes from SARS-CoV-2 infection.
The study also reported on the phenomenon of COVID-19 rebound (recurrence of symptoms and test positivity after regimen completion) after oral outpatient SARS-CoV-2 treatment. “This [COVID-19 rebound] is a downside to treatment,” he said. COVID rebound was not infrequent: A total of 25 (8%) of 318 patients who received oral outpatient treatment had documented COVID-19 rebound.
“It was reassuring because we found no one who had rebound progressed to have severe COVID-19,” Sparks said. “On the other hand, [rebound] happened pretty frequently in our data, as 8% of patients are documented to have it.”
Sparks said he and coinvestigators speculate that more patients in the cohort may have experienced COVID-19 rebound but did not communicate this to their healthcare providers, and, as such, it was not documented in the medical record. The potential development of COVID-19 rebound “is something to counsel your patients about,” he said. COVID-19 rebound is a phenomenon that is being most commonly observed with nirmatrelvir-ritonavir as outpatient treatment.
Possible Confounding Factors in Study
Katie Bechman, MBChB, clinical lecturer in rheumatology at King’s College London in the United Kingdom, who coauthored an accompanying editorial about the study and its findings, pointed out that the study is limited by its observational design.
“With any study that looks at the efficacy of treatment, especially in an observational cohort, you’re going to have to consider the unmeasured confounding and the difference between these two groups,” Bechman said. “I know that they did try to adjust for that in this study, but there’s always going to be factors that we can’t [control for]. That is something that needs to be considered. I think that’s always something we need to consider when we’re looking at observational data.”
In lieu of a randomized, controlled trial, Bechman noted that the study and its associated findings serve as “the best data we have,” and she described the results as “very informative and positive.”
She added that the large number of patients represents a strength of the study, as does the robust method employed for identifying which patients had COVID-19.
The learnings from this study with respect to outpatient treatment can be applied to more common illnesses that patients with rheumatic disease may develop, such as the flu, according to Bechman.
“One of the positive aspects from this pandemic is that we’ve learned a huge amount about how best to treat certain viruses and prevent them in patients,” she said. “It would be worth thinking towards the future, what we can do for illnesses that we see very commonly in these populations. There may be treatment regimens that we haven’t really considered until now. You could hypothesize that in the next couple of years, if we have an influenza breakout, that we should be providing some prehospital antiviral treatment to patients, especially the ones that are at high risk.”
Lancet Rheumatol. Published online January 23, 2023. Full text, Editorial
The study was conducted without outside funding. Sparks has received research support from Bristol-Myers Squibb and consulted for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer unrelated to this work. Bechman reported no relevant financial relationships.
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