Long-Term Rituximab Safety in Rheumatoid Arthritis
Ronald F. van Vollenhoven, MD, PhD, chief of the Unit for Clinical Therapy Research, Inflammatory Diseases at the Karolinska Institute in Stockholm, Sweden, and colleagues evaluated the long-term safety of rituximab (RTX) in patients who have had moderate to severe, active rheumatoid arthritis (RA) for up to 11 years.1
Patients were on combination treatment with RTX and methotrexate (MTX). This study was a pooled case analysis of patients in a global clinical trial program that included eight randomized clinical trials; two long-term, open-label extensions; and one open-label prospective study.
As of September 2012, 3,595 patients had received a mean of four RTX courses (range 1–20) over 11 years. Of these 3,595 patients, 1,246 had more than five years of follow-up (8,970 PY). A pooled placebo population (n=818) was included in the analysis.
Adverse event (AE) and serious adverse event (SAE) data were similar among all populations: RTX all exposure (n=3,595), RTX long term (n=1,246) and placebo treated (n=818). The overall serious infection event (SIE) rate was 3.76/100 patient-years (PY; 2.71/100 PY in patients observed for over five years). This result was comparable to previously reported rates at 9.5 years (3.94/100 PY and 3.26/100 PY, respectively).
Serious opportunistic infection rates were rare. Cardiac event rates remained consistent with previous analyses and similar to rates in the general RA population. The most common cardiac AE was myocardial infarction, which occurred in 51 patients. Most of these patients had at least one risk factor for the event. There was no increased risk of malignancy observed over time. Two hundred and forty-one patients (7%) in the all-exposure population prematurely withdrew from their respective study due to AEs and SAEs. The incidence was higher in the first course of treatment and decreased thereafter with each subsequent treatment course.
This report shows that RTX is well tolerated over time and following multiple courses. No new safety risks were identified, and there was no increase in the rate of any AE type with prolonged RTX exposure for up to 11 years of observation.
FDA Advisory Committee Update
On Sept. 10 at the joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee, members voted 23-to-1 against approving Purdue Pharma’s Avridi, the first potential immediate release (IR) oxycodone tablet with abuse-deterrent properties.2 Research showed that participants who took this formulation after meals had a lower oxycodone serum concentration with a delayed analgesic effect.
Research also showed that individuals intending to misuse the formulation by snorting or injecting it would not be able to get high. The Advisory Committee members had concerns this feature might lead patients to take more of the drug for an analgesic effect and accidentally overdose. One committee member stated that Purdue has created a product with deterrent properties (which is needed), but this product is inferior to the already marketed analgesic.
According to Purdue and the FDA, IR oxycodone is the most abused opioid and single-entity IR oxycodone is also the most prescribed, accounting for approximately 15 million prescriptions in 2014.
At the same Advisory Committee meeting, members voted unanimously in favor of approving Xtampza ER (oxycodone extended-release capsules) for managing pain severe enough to require daily, long-term opioid treatment for which alternative treatments are inadequate.3 The Prescription Drug User Fee Act date is Oct. 12, 2015, completing the new drug application review.
Collegium, the drug’s manufacturer, developed this formulation using its proprietary DETERx abuse-deterrent technology to address common abuse methods, including chewing, crushing, dissolving, taking it orally or snorting or injecting the formulation.
For patients with dysphagia or who require feeding tubes, the drug can be removed from the capsule and sprinkled on food, directly into the mouth or administered through feeding tubes, without compromising its release profile, safety or abuse-deterrent characteristics.
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
- van Vollenhoven RF, Fleischmann RM, Furst DE, et al. Long-term safety of Rituximab: Final report of the rheumatoid arthritis global clinical trial program over 11 years. J Rheumatol. 2015 Aug 15. pii: jrheum.150051. [Epub ahead of print]
- Ault A. FDA panel recommends against first IR antiabuse oxycodone. Medscape. 2015 Sep 11.
- Collegium Pharmaceutical. New release: Collegium announces FDA advisory committees unanimously recommend approval of xtampza ER, an abuse-deterrent analgesic for chronic pain. 2015 Sep 11.