A new class of psoriasis drugs did not show a statistically significant increase in the risk of cardiovascular problems, but the meta-analysis may not have been sufficiently powered to allay concerns that anti-IL-12/23 therapies are unlikely to harm the heart. The results not long after Abbott Laboratories yanked pulled its application for such a drug after concerns raised by the FDA.

In fact, Abbott Laboratories last month discontinued all clinical trials of that drug, which is known as briakinumab, pending further investigations relating to possible “mechanistic links” to major cardiovascular adverse events, according to the analysis in the latest issue of the Journal of the American Medical Association.

“Until more definitive data become available, we believe that dermatologists should exercise heightened vigilance for cardiovascular risk factors when initiating anti–IL-12/23 agents in psoriasis patients,” the researchers write (here is the abstract).

Although this new type of drug has shown to be effective at treating psoriasis, patients with severe forms of the malady are at increased risk of heart attacks. “We’re concerned about the apparent excess in cardiovascular events,” lead study author Caitriona Ryan of the Baylor Research Institute in Dallas tells Reuters.

The meta-analysis reviewed data from 22 randomized clinical trials of anti-IL-12/23 and the older class of anti-TNF drugs to treat chronic plaque psoriasis, which is the most common form. The newer treatments target different proteins than the anti-TNF class, which would include Abbott’s Humira, Johnson & Johnons’ Remicade and Enbrel, which is sold by Pfizer and Amgen.

The analysis found that 10 of 3,179 patients who were treated with anti-IL-12/23 had a major cardiac event, such as a heart attack, stroke or death related to heart disease, compared with no heart problems in the 1,474 patients treated with a placebo. Among patients treated with anti-TNF drugs, 1 of 3,858 patients had a major cardiac problem compared with 1 of 1,812 patients given placebo.

“There are some safety signals you are seeing in the treatment groups that are not in the placebo groups. I’m not saying there is a definite association, but there is smoke here,” Christopher Ritchlin, a rheumatologist at the University of Rochester Medical Center, tells Reutes. He reviewed the findings, but was not involved in the study.

In discussing the findings, Ryan tells Reuters that flaws in clinical trial design are troublesome and warrant additional scrutinty, because these were powered to show differences in the effectiveness of drugs, but not identify rare safety problems. The JAMA study, for instance, cites various limitations that the researchers, many of whom have financial ties to drugmakers, found troubling.

“Limitations of this study,” they wrote, “prevent us from determining whether these drugs expose psoriasis patients to increased cardiovascular risk.” They listed access to patient-level data for the studies was not granted by any of the study sponsors, “which precluded the use of a more statistically robust time-to-event analysis.”

They also cited a small number of major cardiovascular adverse events that occurred in placebo-controlled phases of the studies and a limited duration of the placebo-controlled phases, which reduce the power of the meta-analysis to detect a change in risk.

“The results of all suitable nonpublished completed studies registered with the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were procured through abstract publications or poster presentations in the public domain. Although publications of all studies included reported adverse events, including serious adverse events, failure to report serious adverse events in these publications may constitute another source of publication bias,” they continue.

“A myocardial infarction in an infliximab-treated patient and a myocardial infarction in a placebo-treated patient were not reported in the serious adverse event sections of publications of phase 3 infliximab studies.​ There also may be a temporal effect biasing the results of our meta-analysis, as the majority of the anti–TNF studies were conducted in a time when there was less vigilance for adverse cardiac events in clinical studies. For example, all potential cardiovascular events that occurred in phase 2 and 3 studies of anti–IL-12/23 agents were adjudicated by a team of cardiology experts.”