TNFi use carries only modest increase in psoriasis risk

The use of tumour necrosis factor-α inhibitor (TNFi) for inflammatory bowel disease (IBD) or rheumatoid arthritis (RA) raises the risk of developing psoriasis by twofold as compared with conventional therapy, although the absolute risk remains modest, as reported in a study.

In a cohort of 109,085 patients (median age 50 years, 62 percent female) followed for up to 5 years, “nonpustular types of TNFi-associated psoriasis constituted the most events, whereas pustular types of TNFi-associated psoriasis had the highest relative risk with a sixfold increase,” according to the investigators.

A total of 1,471 (1.4 percent) patients developed any type of psoriasis during the follow-up, of which 1,332 had nonpustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis. The incidence rates for developing any type of psoriasis were 3.0 per 1,000 patient-years with conventional therapy and 7.8 per 1,000 patient-years with TNFi. [JAMA Dermatol 2022;doi:10.1001/jamadermatol.2022.2360]

TNFi treatment conferred a twofold higher risk of nonpustular psoriasis (hazard ratio [HR], 2.12, 95 percent confidence interval CI, 1.87–2.40; p<0.001) and more than sixfold higher risk of pustular psoriasis (HR, 6.50, 95 percent CI, 4.60–9.23; p<0.001) relative to conventional treatment.

“Nevertheless, new-onset psoriasis due to TNFi treatment was a rare adverse event with the lowest estimate of exposure needed for one additional event of approximately 250 patient-years of TNFi treatment and an estimated absolute risk difference around five per 1,000 patient-years,” the investigators pointed out. 

For nonpustular and pustular psoriasis, the exposure needed for one additional patient to be harmed was 342 and 909 patient-years, respectively.

“We observed that psoriasis during treatment with TNFi occurred throughout the entire treatment period and that the median time until development of new-onset psoriasis was estimated to be a little more than a year, in line with previous studies,” according to the investigators. [J Am Acad Dermatol 2017;76:334-341; Inflamm Bowel Dis 2016;22:894-901; J Am Acad Dermatol 2020;83:1590-1598] 

However, they noted that the previous studies reported a significantly higher proportion of palmoplantar pustulosis, about 30–40 percent of all TNFi-associated psoriasis cases, compared with the present data. This discrepancy, they said, is a possible consequence of patient selection and the definitions of new-onset psoriasis, where cases of misdiagnosis may have occurred. [Inflamm Bowel Dis 2016;22:894-901; J Am Acad Dermatol 2020;83:1590-1598; Clin Gastroenterol Hepatol 2010;8:1048-1055]

In the current study, 108,024 received conventional therapy and 20,910 received TNFi treatment. An additional 4,909 patients received non-TNFi biologics. There were 18,167 patients who received more than one type of therapy during the follow-up period, and 2,756 patients received concomitant therapy—conventional and TNFi treatment at the same time. 

“To our knowledge, no other study has been able to include this high number of patients and cases with both IBD and RA, exclude patients with established psoriasis, compare patients treated with a TNFi to a relevant group of patients receiving conventional treatment (control group), and complete sensitivity analyses including patients receiving non-TNFi biological therapy. This thus allowed the current study to estimate the relative risk and absolute risk of new-onset psoriasis in patients with IBD or RA receiving TNFi treatment with greater certainty than previous attempts as well as assessing the exposure needed for one additional event,” the investigators said.

The takeaway, according to the investigators, is that while practitioners and patients should be aware and observant of the potential for developing psoriasis during TNFi treatment, they have to keep in mind that the absolute risk appears to be low.