MTX treatment break improves COVID-19 booster response in patients with IMIDs

In individuals with immune-mediated inflammatory diseases (IMIDs*), a 2-week interruption in methotrexate (MTX) treatment led to enhanced COVID-19 booster vaccine response compared with those who continued with MTX treatment, according to findings from the VROOM** study.

Researchers evaluated 254 adults (mean age 59.1 years, 61 percent female) who had been diagnosed with an IMID and were on low-dose weekly MTX (≤25 mg) for at least 3 months. Participants should have received two primary COVID-19 vaccine doses. Ninety-four percent of participants received an mRNA as COVID-19 vaccine booster. They were randomized 1:1 to either suspend MTX use for 2 weeks immediately after the booster or to continue MTX treatment as usual. [Lancet Respir Med 2022;doi:S2213-2600(22)00186-2]

“A 2-week interruption of MTX treatment immediately after COVID-19 vaccination with a booster vaccine dose resulted in [an] increase in S1-RBD*** antibody response at 4 weeks,” said the researchers. The S1-RBD antibody geometric mean titre (GMT) was higher among those who suspended vs continued MTX (22,750 vs 10,798 U/mL), generating a geometric mean ratio (GMR) of 2.19 (p<0.0001). “[This represents a] more than twofold increase in S1-RBD antibody binding,” they explained.

Moreover, the enhanced antibody response was maintained at 12 weeks (GMT, 16,520 vs 8,094 U/mL), with a GMR of 2.11 (p<0.0001). “[T]he S1-RBD antibody titre in the suspend-MTX arm at 12 weeks was actually greater than that in the continue-MTX arm at 4 weeks,” they pointed out.

The increased antibody response at week 4 among those who suspended MTX was also consistent across the evaluated subgroups^#, they added.

More participants on suspended vs continued MTX self-reported at least one disease flare over 12 weeks (71 percent vs 45 percent; odds ratio, 2.83). Nonetheless, most flares were short-term and self-managed, with only a little over 10 percent of the overall cohort seeking medical assistance for flare management. The flares also did not impair the patients’ quality of life.

No intervention-related serious adverse events were reported, nor were there any deaths during follow-up.

Optimizing durable vaccine protection

Improving vaccine-induced immunity of immunosuppressed individuals remains a challenge, especially at this stage in the COVID-19 pandemic. Moreover, the immunosuppressive effects of MTX temper vaccine-induced responses against COVID-19. [Lancet Rheumatol 2021;3:e627-e637; Ann Rheum Dis 2021;80:1339-1344]

“[As such,] it is important to optimize durable vaccine protection in those who are potentially susceptible through immune suppression,” said the researchers.

Apart from the benefit to policymakers and committees making recommendations on MTX use, the findings “will help patients and clinicians make informed choices about the risks and benefits of interrupting MTX treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” said the researchers.

“[C]linicians and patients will have to balance the possible risk of flare-ups against the benefit of enhanced protection against COVID-19,” they continued. “The decision to suspend MTX treatment in the context of COVID-19 vaccination would be best made following an informed discussion between patient and clinician, taking into account patient preference, disease stability, and previous experience with treatment interruptions.”

MTX interruption is low-cost, easy to implement, and may translate to improved vaccine efficacy and duration of protection for susceptible individuals, they added.

The potential of treatment breaks with other similarly acting immunosuppressive agents to improve vaccine-induced immunity should be explored in future trials.