PMID- 21174485
OWN - NLM
STAT- MEDLINE
DCOM- 20110331
LR  - 20211020
IS  - 1179-1969 (Electronic)
IS  - 1170-229X (Linking)
VI  - 28
IP  - 1
DP  - 2011 Jan 1
TI  - 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.
PG  - 27-40
LID - 10.2165/11584880-000000000-00000 [doi]
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 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.
FAU - Baraf, Herbert S B
AU  - Baraf HS
AD  - Center for Rheumatology and Bone Research, a division of the Arthritis and 
      Rheumatism Associates, Wheaton, Maryland, USA.
FAU - Gloth, F Michael
AU  - Gloth FM
FAU - Barthel, H Richard
AU  - Barthel HR
FAU - Gold, Morris S
AU  - Gold MS
FAU - Altman, Roy D
AU  - Altman RD
LA  - eng
SI  - ClinicalTrials.gov/NCT00171626
SI  - ClinicalTrials.gov/NCT00171678
SI  - ClinicalTrials.gov/NCT00426621
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Drugs Aging
JT  - Drugs & aging
JID - 9102074
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Gels)
RN  - 144O8QL0L1 (Diclofenac)
SB  - IM
MH  - Administration, Cutaneous
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Analysis of Variance
MH  - Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Diclofenac/administration & dosage/adverse effects/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Gels
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Osteoarthritis, Knee/*drug therapy
MH  - Pain Measurement
MH  - Randomized Controlled Trials as Topic
MH  - Treatment Outcome
MH  - United States
EDAT- 2010/12/23 06:00
MHDA- 2011/04/01 06:00
CRDT- 2010/12/23 06:00
PHST- 2010/12/23 06:00 [entrez]
PHST- 2010/12/23 06:00 [pubmed]
PHST- 2011/04/01 06:00 [medline]
AID - 3 [pii]
AID - 10.2165/11584880-000000000-00000 [doi]
PST - ppublish
SO  - Drugs Aging. 2011 Jan 1;28(1):27-40. doi: 10.2165/11584880-000000000-00000.