But findings fall short of benefit reported in RCT

In a comparative effectiveness study using data culled from “real world” clinical practice, secukinumab appeared to be more effective than ustekinumab in treating psoriasis, researchers reported.

Their comparative effectiveness study, which used observational data to replicate a randomized trial. found that secukinumab resulted in more patients achieving a PASI of 2 or lower after 12 months of therapy compared with ustekinumab in patients with psoriasis.

But, the efficacy of both therapies failed to reach the level reported in a randomized clinical trials.

The study, led by Zenas Z. N. Yiu, PhD, University of Manchester, Manchester, U.K., was published in JAMA Dermatology.

The authors noted that while randomized control trials are the barometer for establishing a standard level of efficacy in a treatment, these have limitations. For example, drug manufacturers are not likely to test their products head-to-head with competing products unless they are confident their’s will prove superior. In addition randomized control trials comparing the efficacy of nonbiologic systemic therapies is lacking, and further, they often don’t reflect outcomes seen in real-world settings.

Here, the authors performed a study comparing the effectiveness of the immunomodulators secukinumab (Cosentyx) and ustekinumab (Stelara) by using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) to replicate the CLEAR trial (a randomized clinical trial that compared secukinumab with ustekinumab for psoriasis).

This trial included 1231 patients 18 years or older from the U.K. and Ireland with moderate to severe plaque psoriasis, and at least 1 record of a Psoriasis Area and Severity Index (PASI) of 12 or higher before begin treated with secukinumab or ustekinumab.

The primary outcomes were the risk ratio and the risk difference for achieving PASI of 2 or lower after 12 months of therapy for the ustekinumab cohort (917 patients) and secukinumab cohort 314 patients). Methods used to account for missing outcome data were complete case analysis, nonresponder imputation, last observation carried forward, inverse probability of censoring weighting, and multiple imputation.

PASI at 12 months was recorded for 132 participants (42.0%) in the secukinumab cohort and 417 participants (45.5%) in the ustekinumab cohort. In addition, there were few serious adverse events experienced in either group.

Yiu and colleagues found that the proportion of patients who achieved the primary outcome was lower in this study compared with the CLEAR trial, regardless of the methods used for confounding adjustment or outcome imputation.

Secukinumab outperformed ustekinumab in all analyses — except under the nonresponder imputation method — in the proportion of patients achieving PASI 2 in 12 months (propensity score-weighted complete case analysis: risk ratio 1.28 [95% CI, 1.06-1.55]; risk difference, 11.9% [1.6-22.1]).

Using the point estimate from the complete case analysis under PS weighting, Yiu and colleagues observed reductions of 17.5% and 15.1% for secukinumab and ustekinumab, respectively, between efficacy and effectiveness using the 12-month end point.

“Patients and clinicians should, therefore, be informed that the probability of achieving a PASI of 2 or lower or PASI 90 was lower for both secukinumab and ustekinumab cohorts in the real world than the odds reported in the CLEAR trial, and secukinumab had statistically superior effectiveness compared with ustekinumab,” they wrote. “When counseling patients about the likely outcome of biologic therapies on the basis of figures from clinical trials, clinicians should include a caveat that the real world outcome may be around 15% lower than that found in clinical trials.”

The authors wrote that while there appears to be a gap between the efficacy of biologic therapies in clinical trial settings and their effectiveness in real-world clinical settings regarding the treatment of psoriasis, a target trial method using observational data (such as that from the British Association of Dermatologists Biologics and Immunomodulators Register) can provide robust estimates of treatment effectiveness.

“As a result, we believe that clinicians can interpret other or future comparative effectiveness studies with a target trial framework with confidence and use this information in shared decision-making as an adjunct to data from RCTs,” they concluded.

  1. A study using observational data to replicate a randomized clinical trial comparing secukinumab and ustekinumab found that secukinumab is more effective than Ustekinumab in treating psoriasis in a real-world setting.

  2. The study, however, found that both secukinumab and ustekinumab are less effective in real-world practice than in a randomized control trial setting.

Michael Bassett, Contributing Writer, BreakingMED™

Yiu reported no disclosures

Cat ID: 10

Topic ID: 75,10,10,105,192,919,923