Ustekinumab Safe and Effective for the Treatment of Plaque Psoriasis

The authors of “Long-Term Efficacy, Safety and Drug Survival of Ustekinumab in a Spanish Cohort of Patients with Moderate to Severe Plaque Psoriasis,” published in Dermatology, evaluated the efficacy and safety of ustekinumab in clinical practice and looked at several factors that may affect treatment response rates.

For the study, the authors reviewed the records of 67 patients with moderate to severe plaque psoriasis who received treatment with ustekinumab for at least 28 weeks and a maximum of 3 years at the Department of Dermatology of the Hospital de la Santa Creu i Sant Pau in Barcelona, Spain.

Patients were candidates for treatment “if they had been previously diagnosed of having moderate-severe chronic plaque psoriasis, with a PASI ≥10 or a body surface area ≥10%, and had shown either failure to respond to, or a contraindication to, or intolerance to cyclosporine, methotrexate, photochemotherapy or another biological treatment.”

Patients were evaluated using the Psoriasis Area and Severity Index (PASI) at baseline, and then “at follow-up visits on weeks 16, 28, 36, 50 (year 1), year 2, and year 3 of treatment.” The primary measure of efficacy was the percentage of patients achieving ≥75% improvement in PASI (PASI75 response) at week 28. Researchers also tracked the PASI50 and PASI90 response rates.

Patients were deemed to be primary treatment nonresponders if they were unable to achieve a PASI50 response at week 28 of treatment. Secondary treatment failure was defined as loss of the PASI50 response at any time during the study.

At baseline, mean PASI was 15.7 (range 7-34), with higher mean scores observed in men, obese patients, and in patients weighing >100 kg and treated with 90 mg of ustekinumab.

A large percentage of this cohort had one or more comorbid conditions: 8 patients had psoriatic arthritis, 12 patients had hypertension, 6 had congestive heart failure, 3 had a previous myocardial infarction, 10 had diabetes mellitus, 5 had chronic obstructive pulmonary disease (COPD), 2 had chronic renal failure, 7 had non-alcohol-induced steatohepatitis, and 4 had chronic hepatitis C virus infection. Other comorbid conditions reported included history of alcohol abuse, latent tuberculosis, hyperuricemia, gout, polycythemia, hemochromatosis, autoimmune hepatitis, hypothyroidism and monoclonal gammopathy of undetermined significance.

All participants had previously received at least one systemic treatment, including biologics such as adalimumab, efalizumab, etanercept, and infliximab. Patients were followed for a mean duration of 20.2 months. The authors reported that 65 patients (97.0%) completed treatment through week 36, 49 patients (73.1%) through year 1, 41 (61.2%) through year 2 and 22 (32.8%) through year 3.

Nearly two-thirds of patients achieved PASI75 responses as early as week 16, with sustained response in more than 80% of patients treated for up to 2 years. The authors reported that “PASI90 response rates were 45% as early as week 16, increased up to 78% at 1 year and remained around 65% in patients treated for up to 3 years.”

Female patients experienced significantly higher PASI75 response rates at week 28 and PASI50 response rates at week 36 compared with their male counterparts. Patients who weighed more than 100 kg had lower response rates at all time points compared to lighter patients.

Patients who had not received prior treatment with TNF-blocking agents “had significantly better PASI75 responses than their counterparts both early (week 16) and late (years 1 and 2 of treatment); they were also more likely to be among the best responders (PASI90) after 1 and 2 years of treatment.”

In their discussion of these results, the authors note that “contrary to what has been reported with anti-TNF agents, previous exposure to this group of biologicals does not appear to have a significant effect on the drug survival of ustekinumab.”

They concluded that “Dose intensification and treatment combination may contribute to achieve and maintain PASI75 and PASI90 response in nearly three quarters and two thirds of patients, respectively, beyond 6 months (week 28) of treatment. Male sex, weight >100 kg, obesity and previous failure of one or more TNF inhibitors were associated with a diminished response to treatment, especially as regards long-term PASI90 response rates. Obesity or previous exposure to anti-TNF agents was not associated with a diminished drug survival.”