IL-12/23, IL-23 inhibitors reduce risk for progression to inflammatory arthritis vs. TNFi
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Patients with psoriasis treated with interleukin-12/23 or IL-23 inhibitors may be less likely to progress to inflammatory arthritis than those treated with TNF inhibitors, according to data published in The Lancet Rheumatology.
“Currently, the role of biological immunotherapy in delaying progression from psoriasis to psoriatic arthritis is unclear,” Shikha Singla, MD, of the department of rheumatology at the Medical College of Wisconsin, told Healio. “Prior to our study, four studies showed an association between the time to incident psoriatic arthritis when comparing biological therapy with phototherapy, topical therapy, and conventional synthetic DMARDs. However, none of these studies compared biologics to each other.”
To investigate the impact of various therapies on disease progression from psoriasis to inflammatory arthritis, Singla and colleagues conducted a retrospective cohort study of the TriNetX database, which includes information from patients across the United States. The researchers included patients whose records indicated two or more ICD-9-CM or ICD-10-CM codes for psoriasis. Dates for diagnosis were required to be separated by at least 30 days, and the patient was required to have received a prescription for an FDA-approved biologic for the treatment of psoriasis.
Researchers collected patient information including age at the time of diagnosis, sex, race, ethnicity, marital status, disease duration and date of death. They also accounted for comorbidities such as congestive heart failure, chronic obstructive pulmonary disease, diabetes, liver disease, obesity, tobacco use and renal disease. The main outcome of interest was the first instance of a diagnostic code for inflammatory arthritis at least 2 weeks from the date of the psoriasis diagnosis.
The analysis included a total of 15,501 patients with psoriasis who were diagnosed between Jan. 1, 2014, and June 1, 2022. In all, 976 patients developed inflammatory arthritis, representing a cumulative incidence of 2.6 cases per 100 person-years. According to the researchers, disease progression was “significantly” lower in patients who had received IL-12/23 inhibitors (HR = 0.58; 95% CI, 0.43-0.76) or IL-23 inhibitors (HR = 0.41; 95% CI, 0.17-0.95), compared with patients receiving TNF inhibitors. There was no significant difference between patients prescribed TNF inhibitors and those who received IL-17 inhibitors.
“Our study is the first to describe the associations between classes of biological immunotherapy and the time to incident inflammatory arthritis,” Singla said. “We identified 14 published randomized trials that did head-to-head comparisons of different biologic classes with regards to their effect on psoriasis — these contain data on more than 13,000 patients. Pooled analyses of these data would be adequately powered to confirm the findings of our study.”
Perspective
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We know that one in four patients with psoriasis will develop inflammatory arthritis. Current therapies to treat psoriasis include oral, topical, biologic, oral small molecule and phototherapy. Multiple studies report that treating psoriasis with biologics decreases the risk for developing psoriatic arthritis since they use the same inflammatory pathways.
However, does the choice of DMARD or biologic make a real impact and how can we slow or stop the ultimate development of psoriatic arthritis? The use of TNF inhibitors, IL-12/23, IL-23 and IL-17s have been shown to improve symptoms and prevent progression. Biologic DMARDs have reduced the risk when compared with traditional treatments. However, in this cohort analysis, patients who received TNF inhibitors had the highest probability for arthritis development vs. IL-12/23. Meanwhile, the risk was the same vs. IL-23 or IL-17.
In the cohort studies it took approximately 500 days for the patients to develop arthritis symptoms when they were treated with anti-TNF, IL-23, or IL-17 biologics. The study authors found that patients who were on IL-12/23 inhibitors had a significantly reduced risk for developing arthritis during that same time.
Non-TNF biologics should be taken seriously as first-line therapies for psoriasis. I find this review interesting as it looked at the biologics based on their mechanism of action. Rheumatologists need to work collaboratively with our dermatologist colleagues to think about the bigger picture for patients with psoriasis to stop the progression into inflammatory arthritis.
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