Study investigators observed no significant differences in oxygen supplementation, hospitalization, or COVID-19 related death between initiators and non-initiators, though they cautioned more research was needed.
Treatment with calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) is not associated with risk of SARS-CoV-2 infection or developing severe clinical outcomes from COVID-19 in United States military veterans with migraine disorder, according to the results of a study published in the Journal of the American Medical Association.
Investigators used patient data from the Veterans Health Association’s Headache Centers of Excellence to complete their study. They found there were 354,294 unique veterans who contributed to 8,178,652 person-trials.
Of these veterans, 9992 person-trials initiated CGRP mAb treatment (mean [SD] age, 46.0 [9.5] years; 53.9% men; 46.1% women) and 8,168,660 person-trials that did not initiate CGRP mAbs (46.6 [10.2 years; 65.7% men; 34.3% women).
The primary outcome of this study was the cumulative incidence of SARS-CoV-2 infection. For secondary and exploratory analyses, the study authors examined clinical outcomes related to COVID-19, such as hospitalization, use of mechanical ventilation, or death within 30 days of an index positive SARS-CoV-2 test result, as well as COVID-19 related symptoms and inflammatory markers.
In total, 1247 initiators of CGRP mAb (12.5%) and 780,575 non-initiators (9.6%) tested positive for SARS-CoV-2 from their baseline until May 2022. Additionally, a lower proportion of initiators were hospitalized (55 [4.4%] versus 37,724 [4.8%]), required the use of supplemental oxygen (36 [2.9%] versus 26,153 [3.4%]), or died (2 [0.2%] versus 3594 [0.5%]) within 30 days after the positive test result.
After researchers adjusted for baseline confounders to determine odds ratios (OR) for each subgroup, they found no significant differences between initiators and non-initiators for hospitalization (OR, 0.89; 95% CI, 0.66-1.20), requiring accompanying oxygen (OR, 0.81; 95% CI, 0.57-1.17), or death (OR, 0.53; 95% CI, 0.13-2.13).
In further tailoring their results, the investigators, censored persons who deviated from their assigned treatment. They found that 565 initiators (5.7%) and 771,215 non-initiators (9.4%) tested positive for SARS-CoV-2. Further, the incidence of SARS-CoV-2 infection was 7.4 per 1000 person-months in the initiator group and 6.9 per 1000 person-months for non-inhibitors.
An analysis of clinical outcomes showed that initiators had a higher likelihood to experience COVID-19-related symptoms (354 [62.8%] versus 26,297 [56.3%]; P = .04), such as sore throat and abdominal pain. The researchers determined there were no statistically significant differences in dyspnea between the 2 groups.
The study authors recounted prior research that examined the relationship between CGRP mAbs and COVID-19 that reaffirmed their suggestion that the migraine treatment did not adversely affect those at risk for severe COVID-19. However, they noted some limitations on these trials, and that more clinical evidence was necessary.
Although patients with migraine who were treated with CGRP mAbs had lower ferritin and procalcitonin levels, which indicated better inflammatory profiles and could have been associated with better outcomes, the clinical courses of these patients were no better than controls in terms of hospitalization, oxygen use or death, the researchers found.
Despite this determination, the researchers suggested a cautious interpretation of those results, due to the small number of events that occurred and the fact that CGRP can induce other mechanisms, such as inotropy, that may be beneficial to patients with COVID-19.
Study limitations that the investigators recognized include a 5-month median duration of CGRP mAb treatment, which limited the ability to analyze longer-term outcomes, in addition to the tendency of CGRP mAb initiators to have higher levels of health care seeking behaviors, which could lead to overrepresentation and potentially a false-negative conclusion.
Wang K, Fenton BT, Deng Y, et al. Calcitonin gene–related peptide monoclonal antibodies and risk of SARS-CoV-2 infection and severe COVID-19 outcomes among veterans with migraine disorder. JAMA Netw Open. 2023;6(7):e2326371. doi:10.1001/jamanetworkopen.2023.26371