11 October 2019

First head-to-head trial for rival PsA biologics

Clinical Psoriatic Athritis

A head-to-head trial of two biologics for psoriatic arthritis (PsA) has given rheumatologists a rare insight into which drug could work best for some patients.

It’s relatively uncommon for comparative clinical trials to be conducted on two rival medications, so the results of this study will be received with interest by specialists in Australia.

The study, funded by Eli Lilly and published in the Annals of the Rheumatic Diseases, compares adalimumab and ixekizumab in patients with PsA who did not respond to conventional medication.

These drugs are both biologics; adalimumab is a TNF inhibitor and ixekizumab is a high-affinity monoclonal antibody that selectively targets IL-17A.

Both drugs are PBS-funded in Australia for patients with PsA who do not respond to DMARDs.

In the trial, around 560 patients were randomised to receive either ixekizumab or adalimumab for 24 weeks.

It was an open label trial, so the patients knew which drug they were taking just like they would in real life, but the researchers were blinded to the treatment to reduce bias.

The researchers chose a composite primary endpoint, meaning that the success of the medication was judged as to whether it resulted in a greater than 50% improvement in articular disease from baseline using the American College of Rheumatology (ACR50) criteria as well as a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100), or complete clearing of the skin.

Ixekizumab outperformed adalimumab in the study, with significantly more patients taking this drug achieving the combined endpoint of ACR50 and PASI100 (36% vs 28%).

This difference between the two drugs was observed as early as eight weeks.

While ixekizumab was clearly superior to adalimumab in treating rashes, both drugs had quite similar effects on joints (51% of patients taking ixekizumab achieved ACR50 compared with 47% patients taking adalimumab).

The adverse events for both drugs included infections, injection-site reactions, allergies and cerebrocardiovascular events.

Over the six months, the TNF inhibitor had almost three times as much serious adverse events as the IL-17 inhibitor (8.5% vs 3.5%).

The rates of adverse events aligned with established safety profiles, the researchers said.

“The study was a first and also was unusual in that it used a combined primary endpoint, both the response in psoriasis rash as well as the joints,” said Associate Professor Peter Nash, a rheumatologist at the University of Queensland and a co-author on the study.

“The efficacy was very similar between the two in terms of the effect on joints, but there appeared to be a safety advantage from the IL-17 inhibitor,” he said. “There’s certainly a skin advantage.”

Importantly, the adverse events were different, he said. TNF inhibitors were linked with opportunist infections like Legionella and lymph node TB, whereas IL-17 inhibitors were linked with two cases of inflammatory bowel disease.

If the clinical trial finding “truly stack ups outside of clinical trials” in patients with co-morbidities that would exclude them from trials, then “perhaps the treatment algorithms should be reconsidered and the IL-17 inhibitors used before the TNF inhibitors unless there’s a particular reason to use the TNFs like uveitis or inflammatory bowel disease, he said.

The 12-month results will be presented in a few weeks time at the ACR annual meeting in Atlanta.

Annals of the Rheumatic Diseases 2019, 28 September