COVID-19 vaccine risk-benefit ratio favourable for patients with rheumatic diseases

In the CONVIN-SING* study, there was a favourable risk-benefit ratio for COVID-19 vaccination in individuals with autoimmune inflammatory rheumatic diseases (AIIRD) who have received a COVID-19 mRNA vaccine.

“There was a moderately high rate of AIIRD flares after mRNA vaccination, but there was also improvement in several patients. Severe flares and hospitalization were rare. Thus, vaccination remains safe and highly recommended,” said the researchers.

After a median follow-up of 4.3 months, 18 percent of nearly 5,000 participants flared. Overall, ~12 percent flared within the 3-month period of interest. Median time to flare was 60 days. [J Autoimmun 2023;134:102959]

Twelve percent of the overall cohort had improved disease activity post vaccine. “[This is] reassuring [and] highlights that patients are still able to have better control of their disease over 3 months despite receiving vaccination,” the researchers explained.

Among participants who flared within 3 months, 72 percent required treatment escalation while 6 percent required hospital admission. In this subgroup, the incidence of mild-to-moderate flares was 61 percent. Fourteen percent had severe cases, while 25 percent of flares were self-limiting.

Older participants had a lower risk of flare. The hazard ratios (HRs) for the respective age tertiles of 53–65 and >66 years were 0.6 and 0.7 (p<0.001 for both). “This may be partially attributed to reduced vaccine immunogenicity in the elderly,” said the researchers. “Other factors, such as disease duration, depth and/or length of remission at the time of vaccination and immunosuppressive medications in this population may have also played a part.”

Flare was also more likely among those on csDMARDs**, immunosuppression, and prednisolone ≤7.5 mg (HRs, 1.5, 1.2, and 1.5, respectively]. “[However,] while only 1.4 percent of patients were documented to have withheld their treatment prior to vaccination, this may be an underestimation, leading to more flares in patients pausing higher-dose treatment,” the researchers noted. “[Also,] patients on such therapies are likely on closer follow-up than those who are on minimal treatment … [T]hus, this finding may be due to ascertainment bias.”

Up to 44 percent of patients with AIIRD fear that a COVID-19 vaccine might trigger flares of their condition, said the researchers. “[W]e set up CONVIN-SING to accurately assess flares and risk factors for flares from direct medical record review of all patients with AIIRD attending public sector hospitals in Singapore and who had received an mRNA vaccine against SARS-COV-2.”

CONVIN-SING comprised 4,627 individuals with AIIRD (median age 61 years, 71 percent female, 73 percent Chinese) who had received at least a dose of a COVID-19 mRNA vaccine (~88 percent received the BNT162b2 vaccine). Rheumatoid arthritis was the most common AIIRD (42 percent), followed by systemic lupus erythematosus (14 percent) and psoriatic arthritis (10 percent).

At the pre-vaccination visit, only 1 percent of participants had high disease activity. Ten percent had moderate disease activity, while 41 percent had low disease activity. Nearly 50 percent were in remission.

Potential overestimation

The researchers underscored that arthralgias or myalgias are common post-vaccination effects that lead to tender joints on exam and elevated inflammatory markers. “[These] may contribute toward a higher perceived disease activity, potentially overestimating the observed flare rates.”

Furthermore, the fraction of participants with improved disease activity post vaccination suggests that both flares and improvement may just be a part of the natural history of disease, the researchers continued. “[Nonetheless, this] warrants further study.”

“[Taken together,] given the high morbidity and mortality of COVID-19 in patients with AIIRD, our study strongly supports a favourable risk-benefit ratio for vaccination of these vulnerable patients,” the researchers concluded.