For Safety, One Biologic a Winner in Psoriasis, Psoriatic Arthritis

Patients with psoriasis or psoriatic arthritis who were being treated with ustekinumab (Stelara) had lower rates of serious hospitalized infections than patients receiving other biologics or small molecule therapies, a study utilizing data from two commercial claims databases found.

After propensity score weighting, the incidence rate for infections requiring hospitalization was 0.87 per 100 person-years in MarketScan and 0.84 per 100 in Optum among patients initiating treatment with ustekinumab, according to Seoyoung C. Kim, MD, and colleagues from Brigham and Women’s Hospital/Harvard Medical School in Boston.

In contrast, the incidence rates for the most commonly used biologic, adalimumab (Humira) were 1.19 per 100 person-years in MarketScan and 1.51 per 100 in Optum, the researchers reported online in Arthritis Care & Research.

Numerous drugs are now available for the treatment of psoriasis and psoriatic arthritis, including tumor necrosis factor (TNF) inhibitors, agents that block interleukin (IL)-17, IL-23, and IL-12/23, as well as small targeted molecules such as JAK inhibitors and the PDE-4 inhibitor apremilast (Otezla).

Most previous studies evaluating the safety of these medications have focused on the risks in comparison with conventional disease-modifying antirheumatic drugs (DMARDs) and other traditional agents such as glucocorticoids. Few data are available comparing safety — especially severe, relatively rare events such as serious infections — among the contemporary, widely used biologics and small molecules.

Therefore, to help clinicians and patients in assessing risks among the currently available agents, Kim’s group conducted a population-based cohort study that included 123,383 patients with psoriasis or psoriatic arthritis enrolled in the two databases during the years 2009 to 2017. The cohort included initiators of adalimumab, apremilast, certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), ixekizumab (Taltz), secukinumab (Cosentyx), and ustekinumab.

The primary outcome of interest was hospitalization for bacterial, viral, or opportunistic infection.

Patients’ mean ages ranged from 47 to 53, and the majority were women. Psoriasis alone was the most common diagnosis.

Because in the initial analysis ustekinumab had the lowest incidence rate of hospitalized infections, it was then used as the reference drug for comparison with the other eight medications. The propensity-score weighted hazard ratios for the two combined datasets versus ustekinumab were as follows:

• Adalimumab, HR 1.66 (95% CI 1.34-2.06)

• Apremilast, HR 1.42 (95% CI 1.02-1.96)

• Certolizumab, HR 1.09 (95% CI 0.68-1.75)

• Etanercept, HR 1.39 (95% CI 1.01-1.90)

• Golimumab, HR 1.74 (95% CI 1.00-3.03)

• Infliximab, HR 2.92 (95% CI 1.80-4.72)

• Ixekizumab, HR 2.98 (95% CI 1.20-7.41)

• Secukinumab, HR 1.84 (95% CI 1.24-2.72)

Secondary outcomes included serious bacterial infections and herpes zoster infections. The hazard ratios for serious bacterial infections compared with ustekinumab were similar to the primary outcome:

• Adalimumab, HR 1.60 (95% CI 1.10-2.34)

• Apremilast, HR 1.47 (95% CI 1.01-2.13)

• Certolizumab, HR 0.58 (95% CI 0.31-1.10)

• Etanercept, HR 1.42 (95% CI 1.00-2.03)

• Golimumab, HR 1.75 (95% CI 0.88-3.47)

• Infliximab, HR 2.99 (95% CI 1.90-4.27)

• Ixekizumab, HR 3.31 (95% CI 1.02-10.73)

• Secukinumab, HR 1.62 (95% CI 1.04-2.52)

For herpes zoster, the hazard ratios versus ustekinumab ranged from 0.53 (95% CI 0.27-1.03) for certolizumab to 1.47 (95% CI 0.64-3.36) for golimumab.

“In this large U.S. population-based multi-database cohort study encompassing 123,383 initiators of biologic DMARDs or apremilast for psoriasis/psoriatic arthritis, we consistently observed a lower rate of hospitalized serious infection among ustekinumab initiators compared with TNF inhibitors, IL-17 inhibitors, and apremilast initiators. Risk of herpes zoster infection was similar across the treatment groups,” Kim and colleagues wrote.

The lower risk observed with ustekinumab was an unexpected finding, they noted. They had predicted that the lowest risk would be seen for apremilast, which is classified as an immunomodulating drug, rather than an immunosuppressive.

A possible explanation for this, the researchers said, could be channeling, because patients who were given apremilast typically were older and had more comorbidities. The investigators attempted to account for these differences through propensity score weighting, but there may have been some residual confounding.

An additional limitation of the analysis was a lack of information in the databases on duration of disease or disease activity.

“Future studies are warranted to confirm our findings and explore the mechanisms behind the different infection risks across these agents,” the researchers concluded.