Evaluation of the effectiveness and tolerability of controlled-release diclofenac-potassium versus immediate-release diclofenac-potassium in the treatment of knee osteoarthritis.

Abstract.

BACKGROUND

A controlled-release (CR) form of diclofenac-potassium has been developed, which delivers 100 mg over the course of 24 hours. This formulation is administered QD and provides steady plasmatic levels of the drug.

OBJECTIVE

The aim of this study was to compare the effectiveness and tolerability of CR diclofenac-potassium versus the immediate-release (IR) formulation, when used for treatment of pain in patients with knee osteoarthritis.

METHODS

This prospective, randomized, double-blind, comparative, multi-center, parallel-group study was conducted in male and female patients who had been previously diagnosed with knee osteoarthritis. Inclusion criteria included knee joint pain and ≥3 of the following: age >50 years, morning rigidity lasting <30 minutes, crackling in the joint, pain with applied pressure to the bones, bone hypertrophy, absence of articular heat, and a radiology status of I to III on the Kellgren-Lawrence scale. Patients were randomly divided into 1 of 2 equal-sized groups: 1 group received diclofenac-potassium IR 50 mg BID for 30 days and 1 group received diclofenac-potassium CR 100 mg QD for 30 days. Patients were assessed at baseline and again at 15 and 30 days after initiation of treatment with a physical examination, pain measurement via 100-mm visual analog scale (VAS), and Western Ontario McMaster (WOMAC) osteoarthritis index questionnaire. Adverse events (AEs) were assessed by direct interrogation, hematology controls, blood chemistry, hepatic tests, coagulation tests, and urine tests performed on patients before treatment initiation and on day 30.

RESULTS

Sixty-five patients were screened and 62 patients (mean [SD]age, 61.8 [8.9] years; mean [SD] weight, 71.3 [12.4] kg; female sex, 55 [88.9%]) were included in the study; each study group had 31 patients. After 30 days, both products were equally effective in relieving pain, as measured by VAS (IR, 17.3 vs CR, 21.6; P = NS), and changes in the WOMAC score (IR, 14.5 vs CR, 19.2; P = NS). Significantly more patients in the IR group reported feeling better after 30 days than in the CR group (94% vs 76%; P = 0.002) and, according to the physician's opinion, significantly more patients treated with diclofenac-potassium IR felt better (97% vs 83%; P = 0.03). Significantly more patients in the IR group required rescue medication than those in the CR group (36% vs 26%; P = 0.03). In the CR group, 7 patients experienced AEs: 6 were gastrointestinal (ie, pyrosis, epigastralgia, dyspepsia) and 1 patient experienced increased arterial pressure. One patient from this group discontinued treatment due to a lack of efficacy. In the IR group, 6 patients experienced AEs (ie, tachycardia, epigastralgia, and pyrosis). One patient discontinued because of AEs, and 3 withdrew due to a lack of efficacy.

CONCLUSIONS

Based on the results from this small study in a Venezuelan population, both IR and CR formulations of diclofenac-potassium have similar effectiveness and tolerability profiles.