Submicron Diclofenac Offers "Meaningful" OA Pain Relief in Randomized Trials

A submicron formulation of diclofenac, designed to enable treatment at lower doses than with standard nonsteroidal anti-inflammatory drugs (NSAIDs), offers clinically significant relief from osteoarthritis (OA) pain, compared to placebo, in terms of patient-reported outcomes. These latest results from a 12-week multicenter double-blind randomized trial, were described last week at the Osteoarthritis Society International meeting in Paris.

Rheumatologist Vibeke Strand of Stanford University and others reported analysis of 305 patients with Kellgren-Lawrence Grade II to III hip or knee OA who were assigned randomly to take 35 mg of the submicron diclofenac either twice or three times daily, or placebo, after withdrawing NSAIDs had resulted in a flare.

At either dose level, patients were significantly more likely to report:

•  ≥10 mm reduction in WOMAC (Western Ontario and McMasters Universities Osteoarthritis Index) pain subscale score at 2, 6, and 12 weeks (although more significant pain relief persisted for 12 weeks only at the higher dose),

•   "substantial improvement" in pain (a ≥50% reduction from baseline in WOMAC pain subscale score) at 2 and 6 weeks,

•  at week 12, significant differences in a patient global assessment of pain index compared with placebo,

•  that they felt their status was "very much improved”

Although about half of patients reported at least one adverse event during the 12 weeks of the study, researchers observed none of the serious adverse events normally associated with NSAIDs. The most common adverse events (occurring in 3% of diclofenac and 2% of placebo patients) were diarrhea, upper abdominal pain, and nausea. At the higher dose of the drug there was one occurrence each of elevated alanine aminotransferase and an abnormal liver function test.

The submicron diclofenac, marketed as Zorvolex, has been approved by the FDA for the treatment of mild and moderate acute pain, but not specifically for an osteoarthritis indication, although that application has been filed and is proceeding.