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TitleSafety and efficacy of topical diclofenac sodium gel for knee osteoarthritis in elderly and younger patients: Pooled data from three randomized, double-blind, parallel-group, placebo-controlled, multicentre trials.
AuthorsBaraf HSB, Gloth FM, Barthel HR, Gold MS, Altman RD
SourceDrugs & aging
Date of publication2011
Volume28
Issue1
Pages27-40
AbstractBackground: NSAIDs used for the treatment of osteoarthritis (OA) have dose-related risks for gastrointestinal, cardiovascular and renal adverse events (AEs), particularly in elderly patients. Topical NSAIDs reduce systemic NSAID exposure and may mitigate these risks. Objective: To evaluate the safety and efficacy of topical diclofenac sodium 1% gel (DSG) versus vehicle in patients aged 2564 or >65 years who have been diagnosed with knee OA. Study Design: Pooled data from three 12-week, randomized, double-blind, parallel-group, multicentre trials. Setting: US primary care, internal medicine, orthopaedic and rheumatology practices. Patients: Aged >25 years with mild to moderate (Kellgren-Lawrence grade 13) knee OA. Intervention: After a 1-week analgesic washout, patients applied 4 g of DSG or vehicle four times daily to one knee. Rescue paracetamol (acetaminophen) up to 4 g/day was allowed. Main Outcome Measure: Key efficacy outcomes common to the three trials were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (020) and physical function (068) subscales, global rating of disease (GRD; 100-mm visual analogue scale [VAS]) and pain on movement (POM; 100-mm VAS). ANOVA was used to compare efficacy outcome differences (DSG vs vehicle) by age (2564 or >65 years). A flare design was used that defined a subset of patients who experienced increased pain during the washout period (modified efficacy subpopulation [MES]). Results: The MES included both patients aged 2564 (n = 602) and >65 (n = 374) years. Patients in each age group applied >90% of scheduled doses. Among patients aged 2564 years, the improvement from baseline to week 12 (least squares mean [standard error]) was greater for DSG versus vehicle for WOMACpain (-5.8 [0.3] vs -4.7 [0.3], p = 0.007),WOMACphysical function (-17.9 [0.9] vs -14.2 [0.9], p = 0.002), GRD (-29.5 [1.6] vs -23.8 [1.6], p = 0.01) and POM (-37.3 [1.8] vs -29.0 [1.8], p < 0.001). Among patients aged >65 years, the improvements from baseline for most efficacy outcome scores were significantly greater with DSG versus vehicle: WOMAC pain (-5.3 [0.3] vs -4.1 [0.4], p = 0.02), WOMAC physical function (-15.5 [1.1] vs -11.0 [1.1], p = 0.004) and POM (-33.7 [2.2] vs -26.4 [2.2], p = 0.02). The efficacy of DSG did not differ significantly between patients aged 2564 years and >65 years: WOMAC pain (p = 0.85), WOMAC physical function (p = 0.70), GRD (p = 0.86) and POM(p = 0.81). The incidence of any AE was greater with DSG than with vehicle among patients aged 2564 years (56.6% vs 50.8%) and >65 years (55.8% vs 43.9%). Treatment-related application site dermatitis was more common with DSG compared with vehicle in both younger (4.0% vs 0.7%, respectively) and older (5.8% vs 0.4%, respectively) patients and was the main reason for the difference in treatment-related AEs between the DSG and vehicle groups. Gastrointestinal AEs were infrequent among patients treated with DSG and similar to incidence rates with vehicle in both age groups. Conclusions: DSG was effective and generally well tolerated in adults regardless of age. These data support the topical application of DSG for relief of OA knee pain in elderly and younger patients. Clinicaltrials.gov registration numbers NCT00171626, NCT00171678, NCT00426621. 2011 Adis Data Information BV. All rights reserved.
EMBASE keywords
adult // aged // analysis of variance // application site dermatitis/si [Side Effect] // application site erythema/si [Side Effect] // application site pruritus/si [Side Effect] // article // double blind procedure // drug efficacy // drug safety // drug tolerability // drug treatment failure // drug withdrawal // female // gastrointestinal symptom/si [Side Effect] // human // kellgren lawrence grade // knee arthritis/dt [Drug Therapy] // *knee osteoarthritis/dt [Drug Therapy] // major clinical study // male // multicenter study // patient compliance // primary medical care // priority journal // randomized controlled trial // rating scale // treatment outcome // cyclooxygenase 2 inhibitor/dt [Drug Therapy] // *diclofenac/ct [Clinical Trial] // *diclofenac/ad [Drug Administration] // *diclofenac/dt [Drug Therapy] // *diclofenac/tp [Topical Drug Administration] // *diclofenac sodium gel/ae [Adverse Drug Reaction] // *diclofenac sodium gel/ct [Clinical Trial] // *diclofenac sodium gel/ad [Drug Administration] // *diclofenac sodium gel/dt [Drug Therapy] // *diclofenac sodium gel/tp [Topical Drug Administration] // drug vehicle // nonsteroid antiinflammatory agent/dt [Drug Therapy] // nonsteroid antiinflammatory agent/po [Oral Drug Administration] // paracetamol // unclassified drug
Publisher nameAdis International Ltd (41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10 1311, New Zealand)
City of publicationNew Zealand
Correspondence addressH. S. B. Baraf, Center for Rheumatology and Bone Research, Division of the Arthritis and Rheumatism Associates, Wheaton, MD, United States
Languageeng
Accession NumberEMBASE 2011003245
DOI 10.2165/11584880-000000000-00000
Publication typeJournal: Article
IDCN-00888557