Risk of infection with ANCA-vasculitis cut by antibiotics with Rituximab

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The serious risk of infection associated with rituximab treatment of the associated antineutrophil cytoplasmic antibody (ANCA) vasculitis (AAV) is elevated, but can be offset by co-prescription of co-trimoxazole, data from a single-center retrospective study.

Over a 3-year study period, 14 (28%) of 50 rituximab-treated AAV patients experienced at most one severe infection defined as a grade 3 or higher event. The incidence of serious infections was 15.4 per 100 person-years.

However, a lower rate of infections was observed in patients who had been prescribed co-trimoxazole (trimethoprim and sulfamethoxazole), Francesco Dernie, a fifth-year medical student at Oxford University (England), reported at the annual conference of the British Society for Rheumatology.

“In the case of rituximab, B cell depletion and associated immune suppression is a double-edged sword, which allows for effective disease control, but also leaves the body vulnerable to opportunistic and serious infections.” said Dernie at the meeting.

Of the patients who developed a severe rituximab infection, only 7% had been treated with co-trimoxazole. In comparison, 44% of those who did not have a serious infection had received co-trimoxazole. Multivariate analysis confirmed that co-trimoxazole use was an influential factor, with a probability ratio (OR) of 0.096 (95% confidence interval, 0.009-0.996; Pg = 0.05).

Another finding was that patients with low immunoglobulin G levels (less than 6 g / L) were more likely to develop a severe infection than those with higher IgG levels. In fact, the OR of hypogammaglobulinemia and the risk of infection was 8,782 (95% CI: 1.19–64.6; Pg = .033).

“Our results support monitoring IgG levels to identify patients who may be more susceptible to infection, as well as prescribing prophylactic co-trimoxazole to reduce the overall risk of severe infection,” conclude Dernie and his associated in its summary.

This is a “really important message around co-trimoxazole,” he noted Neil Basu, MBChB, senior clinical professor and honorary consultant at the Institute of Infection, Immunity and Inflammation, University of Glasgow (Scotland).

“I am still frustrated when I see that patients have not received it while receiving rituximab. Of course, co-trimoxazole may have its problems,” said Basu, who did not participate in the study. “It’s not uncommon for patients to develop reactions or be intolerant to the drug.”


Dr. Raashid Luqmani

Raashid Luqmani, DM, co-author of the paper and professor of rheumatology in the Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, Nuffield, Oxford University, said: “Tolerance to co-trimoxazole has been remarkably good in this cohort.” If there is a problem with the use of co-trimoxazole, then “our standard would be to follow it trimethoprim just like the next in line and follow it with inhalation pentamidine. So it’s kind of like following what we would all do in general, ”Luqmani said.

These data add more support for co-prescribing rituximab antibiotic treatment, he suggested.

“Worry about the infection, worry about it a lot; don’t just worry about it, do something about it,” Luqmani said, and co-trimoxazole “is probably an effective way to do something about it.” .

Details of the study

To examine the characteristics and risk factors for serious infections associated with the use of rituximab in AAV, Dernie and his associates retrospectively examined the electronic records of patients who had been treated between August 2016 and August of 2019. Follow-up was until August 2020.

Of the 50 patients identified, almost half (48%) were male. The average age was 60, which ranged from 25 to 90 years. The majority (n = 36; 72%) of the patients had a diagnosis of granulomatosis with polyangiitis, while another 2 (4%) had it microscopic polyangiitis, 1 (2%) had eosinophilic granulomatosis with polyangiitis, and 11 (22%) had an undefined type of overlapping vasculitis or AAV.

Of the 18 events of severe infection recorded, the majority (56%) affected the respiratory tract. Less than a third (28%) were sepsis or neutropenic sepsis, and there was one case each (6%) of cellulite, complicated and recurrent urinary tract infection wound infection.

There were “a small number of individual comorbidities that were not sufficient to enter our regression analysis,” Dernie noted. “Comorbid conditions such as COPD [chronic obstructive pulmonary disease] they also contribute to an individual’s risk of developing serious infections and should therefore be considered for individualized treatment. “

Dernie acknowledged in the discussion, “One of the limitations of the study was that we only looked at patients at a time when they were receiving rituximab, so they could historically have been exposed to other treatment options.” However, he added, “they had no other major DMARDs or immunosuppressive treatments at the time.”

Luqmani noted, “If you look at Francesco’s data on hypogammaglobulinemia at the onset of rituximab, it will probably give you a good idea of ​​how immunosuppressed these patients were before they got to that point.”

Luqmani added: “I suspect this coincides with many other centers that have started using rituximab for patients who previously had episodes of vasculitis treated with other disease-modifying therapies, particularly cyclophosphamide. “

However, how long should co-trimoxazole be administered after the last dose of rituximab? asked the chair of the session, Richard Watts, DM, of Norwich (England), Faculty of Medicine. These data are purely observational, so it’s not possible to say, Dernie noted, “The patients we included as co-trimoxazole appear to be there more or less constantly and permanently,” he said.

What about the best dose? “It’s complicated,” Luqmani said, because “not only do we use co-trimoxazole for prophylaxis, but we often also want to use it for the treatment of vasculitis itself.”

It is very likely that there is a mixture of patients on analysis who have received co-trimoxazole as treatment or prophylaxis, which means different doses, he said.

“It might be interesting to know if there was a difference” between the doses used and the prevention of the infection, Luqmani added, “but I suspect the figures are too small to know.”

Dernie, Luqmani and the other co-authors had no disclosure.

This article originally appeared on MDedge.com, which is part of the Medscape professional network.





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