PMID- 33554694
OWN - NLM
STAT- MEDLINE
DCOM- 20220325
LR  - 20220427
IS  - 2326-3660 (Electronic)
IS  - 0091-3847 (Linking)
VI  - 49
IP  - 4
DP  - 2021 Nov
TI  - Topical nonsteroidal anti-inflammatory drugs in the treatment of knee 
      osteoarthritis: a systematic review and meta-analysis.
PG  - 381-391
LID - 10.1080/00913847.2021.1886573 [doi]
AB  - OBJECTIVE: To compare the efficacy and safety of topical nonsteroidal 
      anti-inflammatory drugs (NSAIDs) against placebo and active controls for 
      improving pain and physical function of patients with knee osteoarthritis (OA). 
      We hypothesize that topical NSAIDs will be safe and effective for relieving 
      symptoms in patients with knee OA. METHODS: The authors performed a systematic 
      review according to the PRISMA guidelines, searching PubMed, EMBASE, and Cochrane 
      databases. Randomized control trials that investigated topical NSAIDs that are 
      widely available in many countries against both placebo and active controls in 
      primary knee osteoarthritis were included. Studies that investigated other 
      treatment modalities or treated nonspecific OA were excluded. A meta-analysis was 
      performed to quantify the effect sizes and heterogeneity of the NSAIDs used. 
      RESULTS: Upon initial search, 259 records were identified with 18 studies 
      remaining after duplicate removal, abstract, and full-text screening. All NSAIDs 
      demonstrated statistically significant reduction in at least one parameter of OA 
      symptoms. The majority of included studies (66.7%) evaluated diclofenac. In the 
      meta-analysis, standardized mean differences (SMD) of topical NSAIDs versus 
      placebo were calculated and interpreted as having moderate effect size for 
      improvement in pain (0.365, 95% confidence interval (CI) 0.240, 0.490) and 
      physical function (0.354, 95% CI 0.268, 0.493). With regard to safety, studies 
      that used patches or dimethyl sulfoxide (DMSO) in the carrier reported a higher 
      incidence of adverse events (AEs) than other carriers. Skin AEs were higher in 
      the treatment group than the placebo group and gastrointestinal AEs were lower in 
      the treatment group than placebo. CONCLUSION: Topical diclofenac and ketoprofen 
      are the most rigorously studied topical NSAIDs in the treatment of knee OA and 
      have demonstrated the most significant reduction in pain and improvement of 
      function. Ibuprofen was effective for pain relief and physical function 
      improvement, but more high-powered studies are needed to make a confident 
      comparison of efficacy. Additionally, the 'carrier' used to deliver the topical 
      NSAID has an impact on the adverse event profile. This has safety implications 
      for prescribers and pharmaceutical development. Topical diclofenac is widely 
      available internationally and is the only topical NSAID approved for 
      over-the-counter use in the US. It should be recommended to patients as a 
      first-line conservative management for OA of the knee.
FAU - Wolff, Dylan G
AU  - Wolff DG
AUID- ORCID: 0000-0002-5257-6111
AD  - Department of Orthopaedics, Tulane University School of Medicine, United States.
FAU - Christophersen, Christy
AU  - Christophersen C
AD  - Department of Orthopaedic Surgery, Mayo Clinic Rochester, United States; 
      Department of Orthopaedics, Tulane University School of Medicine, United States.
FAU - Brown, Symone M
AU  - Brown SM
FAU - Mulcahey, Mary K
AU  - Mulcahey MK
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20210304
PL  - England
TA  - Phys Sportsmed
JT  - The Physician and sportsmedicine
JID - 0427461
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 144O8QL0L1 (Diclofenac)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/adverse effects
MH  - Diclofenac/adverse effects
MH  - Humans
MH  - Knee Joint
MH  - *Osteoarthritis, Knee/drug therapy
MH  - Pain/drug therapy
OTO - NOTNLM
OT  - *Knee osteoarthritis
OT  - *administration
OT  - *agents
OT  - *diclofenac
OT  - *ketoprofen
OT  - *nonsteroidal anti-inflammatory
OT  - *osteoarthritis
OT  - *topical drug
EDAT- 2021/02/09 06:00
MHDA- 2022/03/26 06:00
CRDT- 2021/02/08 08:42
PHST- 2021/02/09 06:00 [pubmed]
PHST- 2022/03/26 06:00 [medline]
PHST- 2021/02/08 08:42 [entrez]
AID - 10.1080/00913847.2021.1886573 [doi]
PST - ppublish
SO  - Phys Sportsmed. 2021 Nov;49(4):381-391. doi: 10.1080/00913847.2021.1886573. Epub 
      2021 Mar 4.