Functional Impact of Adverse Events Associated with Pain Medications

Fort Lauderdale—A post hoc analysis of two phase 3, randomized, double-blind, placebo-controlled trials found that patients with moderate-to-severe chronic low back pain or osteoarthritis of the knee who experienced adverse events during the studies had problems associated with physical functioning, social functioning, mental health, and vitality.

Results were presented during a poster session at the AAPM meeting. The poster was titled Measuring the Functional Impact of Adverse Events.

The authors noted that opioid analgesics are commonly prescribed to treat pain, but adverse events are common and lead to reduced medication adherence, treatment discontinuation, and a reduced health-related quality of life.

In this analysis, the authors examined data from 2 Institutional Review Board-approved trials involving 1988 patients who received tapentadol extended release, oxycodone controlled release, or placebo for 15 weeks.

Tapentadol extended release is FDA-approved to treat adults with moderate-to-severe chronic pain or neuropathic pain associated with diabetic peripheral neuropathy. The FDA has also approved oxycodone controlled release for moderate-to-severe chronic pain.

Both studies collected adverse events from the time patients signed informed consent through their final visit. At each study visit and through spontaneous reporting outside of the visits, patients were asked questions about their adverse events, which were documented in case report forms. The trials also recorded medications used to treat the adverse events and study discontinuations because of adverse events.

The osteoarthritis of the knee trial included men and women who were ≥40 years of age, had used opioid or nonopioid analgesics for at least 3 months before screening, and had an average pain score of at least 5 on an 11-point numerical scale during the last 3 days of an analgesic washout period.

The chronic low back pain trial included men and women who were at least ≥18 years of age, had nonmalignant low back pain for at least 3 months before screening, and had an average pain score of at least 5 on an 11-point numerical scale during the last 3 days of an analgesic washout period.

When combining the trials, the most common function-based adverse events were nausea or vomiting (15.6% of patients), somnolence or fatigue (15.4% of patients), constipation (11.7%), headache or migraine (11.4%), upper respiratory tract infection or nasopharyngitis (11.1%), and pains in the extremity or back pain (10.8%).

In each trial, patients who received oxycodone controlled release had higher rates of constipation, nausea, and dizziness compared with patients who received tapentadol extended release and placebo. They also had higher rates of psychological, vitality-related, and dermatologic treatment-emergent adverse events.

During the study, most patients improved their pain and health-related quality of life as assessed by the 36-Item Short Form Health Survey (SF-36) questionnaire. Compared with the placebo group, patients taking oxycodone controlled release or tapentadol extended release had better pain relief according to the SF-36 results. However, for nonpain SF-36 scales such as physical, role, social functioning, vitality, and mental health, the scores were, on average, 4.8 points lower in patients with adverse events compared with those without adverse events. A higher score on the SF-36 indicates a better health status.

Among the 15 function-based adverse events, constipation, nausea/vomiting, diarrhea, and other gastrointestinal events had the largest negative impact on the SF-36. The effects of the function-based adverse events on SF-36 scores were larger for more severe adverse events and for those requiring medications to treat or those that led to treatment discontinuation, but the effects did not change based on age, treatment, or the patient population.

This poster was supported by Janssen Pharmaceuticals, Inc.