The latest ORAL Surveillance paper on different types of infections details the size of gap.
The latest publication of findings from the ORAL Surveillance trial, this time looking at infections, reports a higher risk of infections among patients on tofacitinib compared with those on TNFi, particularly for herpes zoster infections.
“The current post hoc analysis revealed a higher risk of non-serious infections and herpes zoster with tofacitinib versus TNFi, and higher risk of serious infections with tofacitinib 10 mg two times per day versus TNFi, particularly in patients aged ≥65 years,” the authors wrote.
“These results should be carefully considered as part of shared decision-making between physicians and patients.”
The FDA-mandated post authorisation safety study, which began in 2014, included almost 4,500 RA patients. They were allocated 1:1:1 to 10mg tofacitinib bid, 5 mg tofacitinib bid or TNFi. Patients were at least 50 years old and were required to have at least one cardiovascular risk factor, and all were treated with background methotrexate.
Infection outcomes included in the analysis were all infections, serious infections, non-serious infections, herpes zoster and adjudicated opportunistic infections (including herpes zoster and tuberculosis). Results were reported at ACR 2021 and were published in the Annals of the Rheumatic Diseases.
Just over 70% of patients in the tofacitinib groups reported at least one infection, compared with 64% in the TNFi group. Risk was greater for those on either dose of tofacitinib vs TNFi, and greater for tofacitinib 10mg bid than 5mg bid.
The hazard ratio (HR) for tofacitinib 5mg bid vs TNFi was 1.2 (95% CI 1.10-1.31) and for tofacitinib 10mg bid vs TNFi was 1.36 (95% CI 1.24-1.49). Incidence in the tofacitinib 10mg bid group was higher than the 5mg bid group (HR 1.13, 1.04-1.23). Risk was higher in people aged 65 and over, compared with those aged 50-65.
The most common infections reported were upper respiratory tract infections, bronchitis, urinary tract infections and nasopharyngitis.
Around 12% of patients in both tofacitinib groups had herpes zoster infections, more than three times the rate of the TNFi group, with the difference becoming apparent before the 6-month mark. Incidence rates were higher among those aged 65 and older.
The findings are consistent with real-world data comparing JAK inhibitors with bDMARDs.
“The increased risk of herpes zoster is a class effect, we see that across all JAK inhibitors, and it does need to be taken into consideration,” said Melbourne rheumatologist Associate Professor Andrew Östör.
The incidence rate of serious infections was greatest in the 10mg bid group, and significantly higher than in the TNFi group (HR 1.48, 1.17-1.87). Tofacitinib 5mg bid was numerically higher than TNFi (HR 1.17, 0.92-1.50). The increased risk was more pronounced in people 65 and older.
Baseline risk factors identified for serious infections included increasing age (all groups), chronic lung disease (5mg and TNFi groups) and opioid use (all groups). For non-serious infections they included female sex (all groups), past smoking (5mg group), history of infection (all groups) and history of chronic lung disease (all groups).
“I think we do need to discuss the situation with patients and then decide on an individual basis the benefits of ongoing treatment,” said Professor Östör.
“Many patients have already tried other therapies, including anti-TNFs, and that is why they are now on tofacitinib. Many patients are doing well, and some extremely well on this medication, so it does have to be looked at in context.
“We’ll keep an eye on your cardiovascular health and make sure you’re vaccinated and up to date with that, and monitor for infections,” he said.
There are still questions remaining, said Professor Östör, including whether data can be extrapolated to groups not represented in ORAL Surveillance and to other JAK inhibitors, as the FDA has done.
“I don’t think we can do that. I think we need to look at each drug and each patient population individually,” he said.
“Another question now is whether anti-TNF is actually protective – whether the rate is not because tofacitinib increases the rate but because anti-TNF is more protective in this situation.”
