TY - JOUR
T1 - Safety and efficacy of topical diclofenac sodium gel for knee osteoarthritis in elderly and younger patients
T2 - Pooled data from three randomized, double-blind, parallel-group, placebo-controlled, multicentre trials
AU - Baraf, Herbert S.B.
AU - Gloth, F. Michael
AU - Barthel, H. Richard
AU - Gold, Morris S.
AU - Altman, Roy D.
N1 - Funding Information:
Novartis Consumer Health, Inc., Parsippany, NJ, USA funded the clinical trials. Endo Pharmaceuticals Inc., Chadds Ford, PA, USA funded this post hoc pooled analysis and the editorial support provided by Complete Healthcare Communications, Inc., Chadds Ford, PA, USA.
PY - 2011
Y1 - 2011
N2 - Background: 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.
AB - Background: 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.
KW - Diclofenac, therapeutic use
KW - Elderly
KW - Nonsteroidal-anti-inflammatories, therapeutic use
KW - Osteoarthritis, treatment
KW - Topical
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UR - http://www.scopus.com/inward/citedby.url?scp=78650702121&partnerID=8YFLogxK
U2 - 10.2165/11584880-000000000-00000
DO - 10.2165/11584880-000000000-00000
M3 - Article
C2 - 21174485
AN - SCOPUS:78650702121
SN - 1170-229X
VL - 28
SP - 27
EP - 40
JO - Drugs and Aging
JF - Drugs and Aging
IS - 1
ER -