Study Finds Fewer Severe Infections With Newer Psoriasis Therapies Versus Methotrexate

Patients with psoriasis taking new prescriptions of apremilast, etanercept, and ustekinumab had a decreased rate of serious infection compared with those taking methotrexate, according to an analysis of medical records from 2 large US claims databases.

Providers should consider risk of infection when choosing a systemic treatment for patients with moderate-to-severe psoriasis, according to the researchers, who published their study Friday in JAMA Dermatology.

Researchers examined health insurance claims databases from January 1, 2003, through September 30, 2015, examining new prescription claims for acitretin, adalimumab, apremilast, etanercept, infliximab, methotrexate, or ustekinumab.

The primary outcome was serious infection requiring an inpatient hospital stay; serious infection was defined as a primary inpatient diagnosis code for pneumonia, meningitis/encephalitis, bacteremia/sepsis, cellulitis/soft-tissue infection, endocarditis, pyelonephritis, and septic arthritis/osteoarthritis.

The databases included 31,595 patients in the Optum Clinformatics Data Mart and 76,112 patients in Truven MarketScan.

The study noted that patients using acitretin, apremilast, infliximab, and methotrexate were older and had higher baseline comorbidity scores than patients using the newer, subcutaneous medicines adalimumab, etanercept, and ustekinumab.

The researchers found a decreased rate of overall serious infection in patients using apremilast (hazard ratio [HR], 0.50; 95% CI, 0.26-0.94), etanercept (HR, 0.75; 95% CI, 0.61-0.93), and ustekinumab (HR, 0.65; 95% CI, 0.47-0.89) compared with methotrexate.

The researchers found that the most common types of serious infection were cellulitis, pneumonia, and bacteremia/sepsis among patients taking any systemic medications.

Researchers did not find a different rate of overall infection among users of acitretin, adalimumab, and infliximab compared to methotrexate.

Sub-analysis by type of serious infection showed a significantly increased risk of cellulitis among users of acitretin compared with methotrexate (propensity score-adjusted HR, 1.76; 95% CI, 1.11-2.80).

The finding that ustekinumab had a decreased risk of serious infection is suggestive that biologics more specifically targeted to inflammatory pathways in psoriasis may be both more effective and safer when it comes to risk of infection.

In an email to The Center for Biosimilars®, lead author Erica D. Dommasch, MD, MPH, a dermatologist in the dermatology department at Beth Israel Deaconess Medical Center, said methotrexate is often considered the first-line treatment for patients with moderate-to-severe psoriasis. This is the largest study to date comparing new users of systemic treatments for psoriasis, including different biologics, to patients using methotrexate.

“Prior studies have mostly been underpowered to detect statistically significant differences in the risk of adverse events, such as serious infection, amongst the different treatments for psoriasis,” she wrote.

She also said that most prior studies analyzing the risk of adverse events used data from clinical trials and registries; those patients may be different than the average patient with psoriasis.

“Our study utilized data from commercial health insurance plans, and the results are generalizable to real-world practice in the US,” she said.

Psoriasis affects 125 million people worldwide. Methotrexate, an anti-inflammatory that blocks cells' ability to grow, has been an effective treatment option for patients with more severe disease. But because it acts on all cells of the body, it can result in unwanted side effects, including serious infection. Newer biologics inhibit different types of cytokines, the immune system proteins that play a role in psoriasis. Some of the first biologics, including adalimumab, etanercept, and infliximab, inhibit tumor necrosis factor (TNF)-alpha. Newer biologics are more targeted to the inflammatory pathways involved in psoriasis. These drugs include ustekinumab, which works by blocking interleukin-17 and -23.

Apremilast, a newer nonbiologic systemic treatment for psoriasis, does not directly inhibit inflammatory cytokines and is thought to have no increased risk of infection, but it is generally less effective in treating psoriasis, the researchers said.

The study says providers should consider the risks of infection when prescribing a treatment. But as with most newer drugs that are more specifically targeted to disease, most patients likely face greater costs for the newer therapies compared with methotrexate, which has been around for decades.

“There is a need for further cost-effectiveness studies to determine whether the potentially superior safety profile and efficacy of some of these medications can justify the increased costs,” said Dommasch. “That said, the type of information we have presented in this study Is important for cost-effectiveness analyses. If a medication can prove to be most cost-effective, potentially that could lead to a more evidence-based approach to what insurers are willing to cover. However, at the present moment, patients and providers generally have their choice of medications restricted by what their insurance plans will cover.”

Reference

Dommasch ED, Kim SC, Lee MP, Gagne JJ. Risk of serious infection in patients receiving systemic medications for the treatment of psoriasis [published online May 10, 2019]. JAMA Dermatol. doi:10.1001/jamadermatol.2019.1121.