Infection risk lower with ustekinumab than other biologics, apremilast in PsA, psoriasis
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Patients with psoriasis or psoriatic arthritis treated with ustekinumab demonstrated a 1.4- to 3-times lower risk for hospitalization with serious infections than those who received other biologics or apremilast, according to data.
“The efficacy of biologics and small molecule therapies in PsO/PsA are well established in pre-marketing randomized clinical trials, and the expected patient satisfaction is generally high,” Yinzhu Jin, MPH, of Brigham and Women’s Hospital and Harvard Medical School, in Boston, and colleagues wrote in Arthritis Care & Research. “However, limited information is available on the comparative safety of these biologics and small molecules in patients with PsO/PsA.”
“Several previous observational studies have examined the risk of serious infection in biologic users of PsO/PsA as there are concerns of immunosuppression in targeted therapies,” they added. “Due to serious infections requiring hospitalization are uncommon, most studies lack statistical power. Moreover, majority of previous literatures compared non-biologic [disease-modifying antirheumatic drugs] with biologics, which may not be the most clinically relevant question in an era where clinicians are often in a position to choose one biologic DMARD over another when patients fail to adequately respond to conventional DMARD.”
To compare the risk for serious infections that require hospitalization among patients with PsA or psoriasis starting ustekinumab (Stelara, Janssen), compared with other biologics or apremilast (Otezla, Amgen), Jin and colleagues conducted a population-based cohort study of two large U.S. claims databases. Using the MarketScan and Optum databases, which include longitudinal information on medical and pharmacy claims from a number of different managed care plans, all for commercially insured individuals, the researchers identified 123,282 patients with psoriasis or PsA who started one of the study drugs between Sept. 25, 2009, and Dec. 31, 2018.
A total of 21,679 included patients were ustekinumab initiators. Among the others, 42,252 started with adalimumab (Humira, AbbVie), 14,911 received apremilast, 2,178 initiated certolizumab (Cimzia, UCB), 25,438 were treated with etanercept (Enbrel, Amgen), 2,749 received golimumab (Simponi, Janssen), 1,960 started ixekizumab (Taltz, Eli Lilly & Co.), 5,365 received infliximab (Remicade, Janssen) and 6,851 initiated secukinumab (Cosentyx, Novartis). The median number of multiple entries per unique patient was one, and 21% of patients had more than one treatment episode.
The primary outcome was hospitalized serious infections, including bacterial, viral, or opportunistic varieties. The researchers estimated hazard ratios comparing ustekinumab with the other study drugs, after applying propensity score fine stratification weights for confounding control in each database. In addition, database-specific weighted hazard ratios were combined through meta-analysis.
According to the researchers, there were 1,514 serious infections during a total of 117,744 person-years of follow-up, representing a crude incidence rate of 1.29 per 100 person-years.
After propensity score fine stratification and weighting, the incidence rates of serious infection for ustekinumab ranged from 0.59 to 0.95 per 100 person-years.
Compared with ustekinumab, the combined weighted hazard ratios for serious infections were 1.66 (95% CI, 1.34-2.06) for adalimumab, 1.42 (95% CI, 1.02-1.96) for apremilast, 1.09 (95% CI, 0.68-1.75) for certolizumab, 1.39 (95% CI, 1.01-1.90) for etanercept, 1.74 (95% CI, 1-3.03) for golimumab, 2.92 (95% CI,1.8-4.72) for infliximab, 2.98 (95% CI, 1.2-7.41) for ixekizumab, and 1.84 (95% CI, 1.24-2.72) for secukinumab.
“The absolute incidence rates of hospitalized serious infections were generally low, less than 1 per 100 person-years, after starting biologic drugs or apremilast,” Jin and colleagues wrote. “This study found that other biologics and apremilast were associated with a higher risk of hospitalized serious infections in PsO/PsA when compared with ustekinumab. However, the risk of herpes zoster was not different between ustekinumab and other biologic drugs or apremilast.
“These head-to-head comparisons of biologics and apremilast for PsO or PsA generate important safety profiles of newly available drugs that will lead to a more informed decision making,” they added. “Nonetheless, future studies are warranted to confirm our findings and explore the mechanisms behind the different infection risks across these agents.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
An old country doctor expressed our situation well when he said, “You treat the disease, and then you treat your complications”. In the past 70 years, immunosuppressives have been used to treat diseases starting with cortisone. Almost immediately, complications were detected.
The biggest area of concern with immunosuppression is infection. My first experience with this as a rheumatology fellow was losing a patient with lupus nephritis on an immunosuppressive to PCP. I have seen tuberculosis activation (tuberculous lymphadenitis), intestinal histoplasmosis, herpes encephalitis, aspergillus pneumonia and many other infections on our conventional synthetic, biologic and targeted synthetic DMARDs. Corticosteroids (prednisone dosage >10 mg/d) have repeatedly been seen as a higher risk for infection than any of our DMARDs.
In this big data study, the researchers discovered that ustekinumab had fewer infections than other biologic DMARDs and even apremilast. Prednisone was not an issue in these psoriasis and psoriatic arthritis patients as corticosteroids are not routinely used. There is the risk of a rebound flare of psoriasis with steroid withdrawal. One potential source of error in the conclusions of this study is the length of exposure to the various medications — a problem that has been recently noted in big data studies.
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