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

Herbert S B Baraf, Fred Michael Gloth, H. Richard Barthel, Morris S. Gold, Roy D. Altman

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)27-40
Number of pages14
JournalDrugs & Aging
Volume28
Issue number1
DOIs
StatePublished - 2011

Fingerprint

Knee Osteoarthritis
Diclofenac
Multicenter Studies
Gels
Placebos
Safety
Pain
Non-Steroidal Anti-Inflammatory Agents
Acetaminophen
Osteoarthritis
Age Groups
Incidence
Rheumatology
Ontario
Dermatitis
Pain Measurement
Internal Medicine
Least-Squares Analysis
Visual Analog Scale
Orthopedics

Keywords

  • Diclofenac, therapeutic use
  • Elderly
  • Nonsteroidal-anti-inflammatories, therapeutic use
  • Osteoarthritis, treatment
  • Topical

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Geriatrics and Gerontology

Cite this

@article{d76bd79cc94a43228102f464a16f608e,
title = "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",
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 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.",
keywords = "Diclofenac, therapeutic use, Elderly, Nonsteroidal-anti-inflammatories, therapeutic use, Osteoarthritis, treatment, Topical",
author = "Baraf, {Herbert S B} and Gloth, {Fred Michael} and Barthel, {H. Richard} and Gold, {Morris S.} and Altman, {Roy D.}",
year = "2011",
doi = "10.2165/11584880-000000000-00000",
language = "English (US)",
volume = "28",
pages = "27--40",
journal = "Drugs and Aging",
issn = "1170-229X",
publisher = "Adis International Ltd",
number = "1",

}

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, Fred Michael

AU - Barthel, H. Richard

AU - Gold, Morris S.

AU - Altman, Roy D.

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

UR - http://www.scopus.com/inward/record.url?scp=78650702121&partnerID=8YFLogxK

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

VL - 28

SP - 27

EP - 40

JO - Drugs and Aging

JF - Drugs and Aging

SN - 1170-229X

IS - 1

ER -