AdverseEvents flags TB reports, blood-disorder cases linked to RA drugs

AdverseEvents VP Keith Hoffman

Rheumatoid arthritis is a big moneymaker for pharma companies, and with biosimilars on their way for top-selling meds--and newer therapies coming down the pipeline--competition is going to intensify. But the powerful meds come with their own set of safety issues.

Both TNF-alpha and non-TNF alpha drugs continue to generate side-effect reports, but a new AdverseEvents analysis found that on the whole, anti-TNF meds were safer than their counterparts in other classes. The TNF drugs didn't show many cases of blood disorders, for example, but four out of the 6 non-TNF meds included in the study had elevated reports for one serious blood condition.

Prometheus Labs' non-TNF drug Imuran had 196 cases of the pancytopenia, which involves deficiencies in red and white blood cells as well as platelets. More than 150 cases of the disorder cropped up in patients using Sanofi-Aventis' Arava, and patients using Roche's ($RHHBY) Rituxan had 360 cases. Comparatively, TNF-alpha inhibitors such as UCB's Cimzia and Janssen's Simponi had 13 and 22 cases for pancytopenia each.

Infections of various types cropped up in patients using both types of meds; that's not surprising, given that RA is an auto-immune disease treated by interfering with the immune system. Non-TNF alpha drugs showed "disproportional reporting" for sepsis infection, Keith Hoffman, vice president of scientific affairs at AdverseEvents, told FiercePharma. The firm pointed to 670 cases for Rituxan, 172 cases for Arava and 93 cases for Imuran. Sepsis affected TNF-alpha patients, too, however, with 95 cases for Simponi and 126 for Cimzia.

By contrast, when it comes to upper-respiratory conditions, non-TNF drugs appear to be "a little better" than TNF-alpha meds, Hoffman said. AdverseEvents flagged 1,657 cases of upper respiratory tract infection for AbbVie's ($ABBV) Humira and 3,372 cases for Amgen's ($AMGN) TNF therapy Enbrel. Among non-TNF drugs, the firm turned up the most respiratory problems with Bristol-Myers Squibb's ($BMY) Orencia, at 84 cases. Imuran was linked with 5 cases of upper respiratory tract infection.

Still, TNF alpha and non-TNF alpha drugs overlapped in some key areas. There were elevated reports for herpes infections across all drugs, with AdverseEvents flagging the most herpes-related reports for Pfizer's ($PFE) Xeljanz and UCB's Cimzia out of all the RA meds studied. Both types of drugs were associated with Candida infections, although TNF alphas Enbrel, Humira and Simponi, and non-TNF meds Xeljanz, Orencia and Actemra did not turn up as frequently in those side effect reports.

Perhaps more surprising are the elevated reporting rates for tuberculosis, Hoffman said. TB cases turned up in patients using 9 out of the 11 drugs. Janssen's Remicade had 1,607 TB case reports--the most of any TNF or non-TNF med--and Enbrel had the second highest number, with 508 cases.

"Remicade was an outlier of some interest. It has the highest ROR, over 36," Hoffman said. "We consider that a fairly large signal."

But Janssen is not buying AdverseEvents' numbers. "We routinely review the safety data from our pharmacovigilance program with the FDA on a regular basis and update the label accordingly," the company told FiercePharma in an email.

"In reviewing the report, a number of factors need to be considered for each medication in order to fully understand or accurately interpret the data, including differences in disease states, number of approved indications, administration differences, number of exposed patients, number of doses and overall exposure timeframe," the company said.

- check out the AdverseEvents RA report

Special Reports: Top 10 rheumatoid arthritis drugs 2013 | The 10 best-selling drugs of 2013 - Rituxan/MabThera - Remicade - Enbrel - Humira

Editor's Note: This story was updated with a statement from Janssen.