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Safety 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.
Drugs Aging 2011; 28(1):27-40DA

Abstract

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 25-64 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 1-3) 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 (0-20) and physical function (0-68) 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 (25-64 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 25-64 (n = 602) and ≥65 (n = 374) years. Patients in each age group applied >90% of scheduled doses. Among patients aged 25-64 years, the improvement from baseline to week 12 (least squares mean [standard error]) was greater for DSG versus vehicle for WOMAC pain (-5.8 [0.3] vs -4.7 [0.3], p = 0.007), WOMAC physical 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 25-64 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 25-64 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.

Authors+Show Affiliations

Center for Rheumatology and Bone Research, a division of the Arthritis and Rheumatism Associates, Wheaton, Maryland, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21174485

Citation

Baraf, Herbert S B., et al. "Safety 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." Drugs & Aging, vol. 28, no. 1, 2011, pp. 27-40.
Baraf HS, Gloth FM, Barthel HR, et al. Safety 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. Drugs Aging. 2011;28(1):27-40.
Baraf, H. S., Gloth, F. M., Barthel, H. R., Gold, M. S., & Altman, R. D. (2011). Safety 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. Drugs & Aging, 28(1), pp. 27-40. doi:10.2165/11584880-000000000-00000.
Baraf HS, et al. Safety 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. Drugs Aging. 2011 Jan 1;28(1):27-40. PubMed PMID: 21174485.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety 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. AU - Baraf,Herbert S B, AU - Gloth,F Michael, AU - Barthel,H Richard, AU - Gold,Morris S, AU - Altman,Roy D, PY - 2010/12/23/entrez PY - 2010/12/23/pubmed PY - 2011/4/1/medline SP - 27 EP - 40 JF - Drugs & aging JO - Drugs Aging VL - 28 IS - 1 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 25-64 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 1-3) 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 (0-20) and physical function (0-68) 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 (25-64 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 25-64 (n = 602) and ≥65 (n = 374) years. Patients in each age group applied >90% of scheduled doses. Among patients aged 25-64 years, the improvement from baseline to week 12 (least squares mean [standard error]) was greater for DSG versus vehicle for WOMAC pain (-5.8 [0.3] vs -4.7 [0.3], p = 0.007), WOMAC physical 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 25-64 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 25-64 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. SN - 1179-1969 UR - https://www.unboundmedicine.com/medline/citation/21174485/Safety_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_ L2 - https://dx.doi.org/10.2165/11584880-000000000-00000 DB - PRIME DP - Unbound Medicine ER -