P-110 - Treating Osteoarthritis Pain: How Effective Are Immediate- and Extended-Release Acetaminophen Products?

Abstract Title: Treating Osteoarthritis Pain: How Effective Are Immediate- and Extended-Release Acetaminophen?

Background: Acetaminophen became available as an over the counter (OTC) analgesic in 1959. The FDA approved acetaminophen 650 mg extended-release (ER) for the treatment of mild to moderate pain related to osteoarthritis (OA) in 1994. Johnson & Johnson Consumer Inc (JJCI) databases were searched for OA clinical trials with ≥1 oral, acetaminophen-only treatment arm. Data from 2 previously unpublished clinical trials (Trials 1, 2) and 3 published clinical trials (Trials 3, 4, 5)^1-3 which assessed effectiveness and safety of acetaminophen among individuals with radiographically confirmed hip or knee OA are presented. These trials contain clinical data that inform healthcare professionals of the evidence supporting effectiveness and safety of currently available drugs. All trials were randomized, double blind, active-controlled, multiple-dose, parallel, multicenter, home-use clinical trials with dosing ≥ 4 weeks. Trial 1 was conducted between Feb 1994 and Jun 1995; Trial 2 between Dec 1993 and Nov 1995; Trial 3 between May 2000 and June 2003; Trial 4 between April 2002 and March 2003; Trial 5 between January and November 2004.

Purpose/Objectives: These analyses compared participant-reported outcomes from 5 company-sponsored clinical trials following 1, 2 and 4 weeks of treatment with acetaminophen immediate release (IR) 4000 mg or acetaminophen ER 3900 mg to examine effectiveness and safety of acetaminophen. Participant-reported outcomes included level of OA pain, physical function and assessment of acetaminophen as an analgesic. Safety results were summarized across the trials.

Methods: In each trial, participants were ≥40 years of age; had radiographically confirmed hip or knee OA with secondary pain requiring use of NSAID, acetaminophen, or other analgesic on a regular basis for ≥3 months and positive response to ≥1 agent; pain ≥ moderate intensity on 5-point verbal scale for ≥6 months; able to walk without assistive devices; no history or evidence of other types of arthritis or collagen vascular disease. In Trials 1 and 2, participants reported pain at rest and on walking using a 5-point verbal scale; participants also assessed the trial drug as an analgesic. In Trial 2, participants additionally reported duration of morning stiffness. In Trials 1, 3, 4 and 5, participants reported WOMAC pain, physical function, and stiffness. Acetaminophen efficacy data collected during the initial 4 weeks of treatment were used in these analyses. Participant characteristics and responses to assessment queries are described using means and standard errors (SE) and percentage change from baseline. Adverse events were collected for all participants at each visit and reported by the participants in a daily diary. Pooled adverse events of acetaminophen IR 4000 mg/d and acetaminophen ER 3900 mg/d from these trials are presented.

Results: 856 participants used acetaminophen-IR 4000 mg/d (n=429) or acetaminophen-ER 3900 mg/d (n=427) for treatment of pain related to OA of the hips or knees while participating in 5 home-use clinical trials. In Trial 1, 46 participants, in Trial 2, 96 and in Trial 3, 287 used acetaminophen-IR 4000 mg/d. In Trial 4, 160 participants and in Trial 5, 267 used acetaminophen-ER 3900 mg/d. Across the 5 trials, populations were similar; the majority (57% to 78%) of participants were female and >75% reported moderate or moderately severe pain. All had similar radiographic evidence of hip or knee OA. Participants in Trials 1 and 2 used a 5-point scale to report pain at rest and pain on walking. In Trial 1, participants reported 36% to 39% reductions in pain at rest and 30% to 32% reductions in pain on walking at Weeks 1, 2 and 4. Participants in Trial 2 reported 38% to 48% reductions in pain at rest and 30% to 39% reductions in pain on walking at Weeks 1, 2 and 4. Participants in Trials 1, 3, 4 and 5 reported pain, physical function and stiffness at Week 4 using the WOMAC OA Index. On the WOMAC pain subscale, participants reported 22% (Trial 1), 33% (Trial 3), 38% (Trial 4), and 37% (Trial 5) reductions in pain. On the WOMAC physical function subscale, participants reported 15% (Trial 1), 30% (Trial 3), 35% (Trial 4), and 34% (Trial 5) improvements in physical function. On the WOMAC stiffness scale, participants reported 25% (Trial 1), 30% (Trial 3), 33% (Trial 4), and 33% (Trial 5) improvements in stiffness. Using a 5-point scale, participants in Trials 1, 4 and 5 rated their pain relief as good beginning at Week 1 and continuing through Week 4 (range 1.76 to 2.06). Participants rated acetaminophen as fair to good as an analgesic beginning 1 week after treatment and continuing through Week 4 (range 1.36 to 2.06) in Trials 1, 2 and 4. Headache, abdominal pain, dyspepsia and diarrhea were the most commonly reported adverse events.

Conclusions/Implications for future research and/or clinical care: Review of participant response data from 5 home-use clinical trials confirms the analgesic effectiveness and safety of acetaminophen in the management of moderate to moderately severe pain related to hip and knee OA. Participants reported reductions in pain beginning at the first assessment, one week after starting acetaminophen IR 4000 mg/d to manage their OA pain and continuing throughout the 4 week home-use clinical trials. Responses to the WOMAC OA Index confirmed reductions in pain and improvements in physical function and stiffness among participants taking acetaminophen ER 3900 mg/d. Participant reported responses indicating improved outcomes throughout 4 weeks in these 5 clinical trials inform healthcare professionals as to the effectiveness and safety of acetaminophen IR 4000 mg/d and acetaminophen ER 3900 mg/d.

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