Among patients with inflammatory rheumatic musculoskeletal disease (I-RMD), symptoms may decrease after receiving a COVID-19 vaccine, thanks to a new analysis of more than 7,000 European patients with RMD. It’s now a little easier to predict which patients with inflammatory rheumatic musculoskeletal disease (I-RMD) are likely to experience flare-ups.
According to Dr. Pedro M. Machado of University College London, factors associated with increased relapse rates after vaccination include active disease at the time, female gender, and most importantly, discontinuation of antirheumatic drugs. Or that it involved weight loss. And my colleagues.
They weren’t particularly unexpected. But an analysis of 7,336 patients included in the European Confederation of Rheumatic Coronavirus Vaccines Associations (COVAX) registry published in the journal Rheumatic Diseases also found that when researchers looked for factors that predicted a lower risk of relapse, A surprise came.
These include older adults, use of certain types of disease-modifying antirheumatic drugs (DMARDs), and vaccination with less frequently used COVID-19 vaccine products.
However, some of these associations were no longer significant because Machado et al. restricted their analysis to flares severe enough to warrant increased DMARD doses or new drugs. Using these as endpoints, only moderate to high disease activity and DMARD discontinuation or dose reduction remained significantly predictive of relapse risk. Similarly, only the use of methotrexate or rituximab (Rituxan) was significantly associated with a lower risk of severe relapse.
Most reassuringly, relapses were rare in all subgroups. Less than 4% of enrolled patients suffered a flare-up, and for half of those, the flare-up was not severe enough to require a medication adjustment.
“These findings will help patients, clinicians, and other healthcare professionals make informed decisions regarding the management of I-RMD associated with SARS-CoV-2 vaccination and “This will contribute to the development of the most appropriate vaccination strategy for patients,” Machado’s group concluded.
As with the influenza vaccine, patients and clinicians should weigh the risk of relapse when considering a new round of COVID-19 vaccinations, given that regular booster shots will likely continue to be needed for some time. A deeper understanding is essential. Previous studies have shown some increased risk of relapse after vaccination, Machado et al. observed, but quantitative estimates are unclear, particularly for patient-reported relapses and physician-reported relapses. There is variation between Of note, some guidelines call for discontinuation or reduction of DMARD administration before and after vaccination in hopes of boosting antiviral immune responses.
The COVAX registry recorded physician-reported post-COVID-19 vaccination outcomes for patients with RMD, inflammatory or otherwise, from September 2021 to October 2022. Patients who received a combination of multiple vaccine products and patients who received more than one dose of a single vaccine (the latter because baseline disease activity data were collected only at the first dose).
Patients with any of 29 specific symptoms were included in the analysis. At least 250 patients suffered from rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis, lupus, Sjogren’s syndrome, and polymyalgia rheumatica. RA accounted for more than one-third of the total, and axSpA accounted for one-sixth.
The mean age was approximately 58 years, but this varied somewhat by diagnostic category (older for vasculitis, younger for “other” RMDs not considered joint or connective tissue diseases). . Two-thirds of the group were women, and this also varied by type of condition, with an even higher proportion of women for collagen disease, but less so for vasculitis and “other” non-joint diagnoses.
Well over half of patients had received the Pfizer/BioNTech mRNA vaccine (Comirnaty), with 74% of patients receiving two doses and 43% of patients receiving only one dose. AstraZeneca’s now-withdrawn product used a viral vector expressing SARS-CoV-2 antigens and accounted for 13% of two-dose shots and 9% of one-dose shots. Moderna’s mRNA vaccine (Spikevax) was used in 9% of two-dose regimens and 31% of one-dose regimens. The rest were other products. Although these are not specifically listed in the annual report, vaccines sold by Novavax, Sanofi Pasteur, Valneva and HIPRA, as well as Russian and Chinese vaccines, have been available at various times.
Curiously, it was this “other” group of products that seemed to have the least risk of flaring. Compared to the Pfizer/BioNTech vaccine, the overall recurrence rate for the “other” vaccine was only 10 times lower (OR 0.10, 95% CI 0.01-0.74). There was no significant difference in flare-up rates between the Pfizer/BioNTech and Moderna or AstraZeneca vaccines.
Machado et al. were unable to explain this finding, suggesting that given the small number of patients treated (80), it could have been a statistical coincidence, or that perhaps the group No explanation could be given other than to suggest that he may have been influenced by what he calls “bias.” Also, if only severe flares were counted in the analysis, there would be too few to support meaningful comparisons.
The researchers were also interested in whether the risk of relapse was related to the type of DMARD the patient was taking. This proved to be more beneficial than methotrexate (OR 0.57, 95% CI 0.37-0.90), tumor necrosis factor (TNF) inhibitors (OR 0.55, 95% CI 0.36-0.85), and rituximab (OR 0.27, 95% CI 0.11-0.66), all compared with no anti-rheumatic treatment. When focusing only on severe flares, a reduced risk was still evident with methotrexate and rituximab, but not with TNF inhibitors.
On the other hand, the association with baseline disease activity was counterintuitive. Compared to patients who were in remission at the time of vaccination, patients with low disease activity showed a significantly increased risk of relapse (OR 1.45, 95% CI 1.08 to 1.94), but those with moderate/high disease activity No further increase was seen in sexual patients and was not significant. (OR 1.37, 95% CI 0.97-1.95).
On the other hand, the risk of severe relapse showed that the risk increased with higher disease activity. The odds ratio was 1.47 (95% CI 0.94-2.29) for patients compared with 3.08 (95% CI 1.91-4.97) for the moderate/high activity group. Activity is lower, again compared to patients in remission.
The strongest predictor of relapse risk was DMARD dose discontinuation or reduction (OR 4.76, 95% CI 3.44-6.58 for any relapse, OR 2.24, 95% CI 1.33-3.78 for severe relapse).
The study had a number of limitations. It was limited to Europe, where the range of available vaccines and demographic factors are very different from other regions. Reporting in the COVAX registry was voluntary and somewhat subjective, making it susceptible to various biases. The time period between vaccination and the occurrence of the event was not specified and therefore varied among reports. Finally, some events classified as disease flares may actually have been vaccine reactions, particularly for complaints of joint pain.
John Gever served as Editor-in-Chief from 2014 to 2021. He is now a regular contributor.
disclosure
This study was funded by the European Federation of Rheumatology Societies.
The authors reported relationships with numerous drug and vaccine manufacturers, including Pfizer, Johnson & Johnson/Janssen, and AstraZeneca.
primary source
Records of rheumatic diseases
Reference source: Farisogullari B et al. “Factors associated with disease flare after SARS-CoV-2 vaccination in people with inflammatory rheumatic and musculoskeletal diseases: Results from the EULAR Coronavirus Vaccines Physician-Reported (COVAX) Registry ” Ann Rheum Dis 2024; DOI: 10.1136/ard-2024-225869.
