Patients switch to lower dose of Pfizer's RA pill after safety signal

Pfizer is moving rheumatoid arthritis patients to a lower dose of its blockbuster inflammatory diseases pill Xeljanz in a clinical study, after a safety signal emerged in the trial of patients at high risk of cardiovascular events.

A Janus kinase inhibitor class drug, Pfizer has produced Xeljanz as an oral alternative to injected anti-TNF class drugs such as AbbVie’s Humira (adalimumab) and others, which are approved in a range of inflammatory diseases.

Global sales were nearly $1.8 billion in the full year for 2018, up 32% compared with the previous year, making Xeljanz an important driver of sales growth for Pfizer.

The US pharma said the signal had emerged in the study A3921133, which was required by the FDA as a post-marketing requirement for Xeljanz (tofacitinib).

It is taking action after the study’s Data Safety Monitoring Board warned of a safety signal in a study arm where patients received a twice daily dose at 10mg.

The board noted that in patients treated at the higher dose there was a “statistically and clinically important” difference in occurrence of pulmonary embolism, compared with patients in a control group treated with tumour necrosis factor inhibitor (anti-TNF) drugs.

There was also an increase in overall mortality in the higher dose arm compared with the low-dose and anti-TNF arms.

A3921133 is an open-label study testing safety of Xeljanz at two doses compared with a control group using a tumour necrosis factor inhibitor.

The study was designed to assess cardiovascular risk in patients over 50 years of age and have at least one cardiovascular risk factor.

The 5mg twice daily dose is FDA approved for adults with moderate to severe RA.

Trials in other studies in RA, juvenile idiopathic arthritis, psoriatic arthritis, and ankylosing spondylitis should continue unchanged, the safety board said.

First approved in RA in 2012, Xeljanz is also FDA approved in psoriatic arthritis and ulcerative colitis.

AbbVie is developing a rival JAK class drug, upadicitinib, which has been granted a priority review by the FDA in RA this week.