A 12-week randomized study of topical therapy with three dosages of ketoprofen in Transfersome® gel (IDEA-033) compared with the ketoprofen-free vehicle (TDT 064), in patients with osteoarthritis of the knee A Randomized, Double-blind, Phase III Trial in Moderate Osteoarthritis Knee Pain Comparing Topical Ketoprofen Gel with Ketoprofen-free Gel A multiple-dose, open-label, safety, compliance, and usage evaluation study of epicutaneously applied Diractin (ketoprofen in Transfersome) in joint/musculoskeletal pain or soft tissue inflammation. Topical analgesics for knee arthrosis: a parallel study of ketoprofen gel and diclofenac emulgel. A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis. Efficacy and safety of epicutaneous ketoprofen in Transfersome (IDEA-033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial Efficacy of epicutaneous Diractin® (ketoprofen in Transfersome® gel) for the treatment of pain related to eccentric muscle contractions Local NSAID gel (eltenac) in the treatment of osteoarthritis of the knee. A double blind study comparing eltenac with oral diclofenac and placebo gel. The effects of nonsteroidal anti-inflammatory drugs on clinical outcomes, synovial fluid cytokine concentration and signal transduction pathways in knee osteoarthritis. A randomized open label trial. A comparative subjective assessment study of PENNSAID® and Voltaren Gel®, two topical formulations of diclofenac sodium. Ketoprofen 2.5% gel versus placebo gel in the treatment of acute soft tissue injuries. Topical Ketoprofen Patch (100 mg) for the Treatment of Ankle Sprain: A Randomized, Double-Blind, Placebo-Controlled Study Local tolerability and effectiveness of Ketospray® 10% cutaneous spray solution. Safety and Efficacy of Topical Diclofenac Sodium Gel for Knee Osteoarthritis in Elderly and Younger Patients Efficacy and safety of a topical diclofenac solution (pennsaid) in the treatment of primary osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled clinical trial. Randomized controlled trial of diclofenac sodium gel in knee osteoarthritis. A controlled clinical investigation of 3% diclofenac/2.5% sodium hyaluronate topical gel in the treatment of uncontrolled pain in chronic oral NSAID users with osteoarthritis.
Objective To evaluate the safety and efficacy of ketoprofen in Transfersome ® gel ( IDEA-033 ) in comparison with a ketoprofen-free vehicle ( TDT 064 ) for the treatment of osteoarthritis ( OA ) of the knee . Methods Patients with knee OA ( N = 866 ) were r and omly assigned to receive topical IDEA-033 containing 100 , 50 , or 25 mg ketoprofen , or TDT 064 twice daily for 12 weeks , in a double-blind trial . The primary efficacy endpoint was the change in the Western Ontario and McMaster Universities ( WOMAC ® ) Osteoarthritis Index pain subscale score . The co primary efficacy endpoints were the WOMAC function subscale score and the patient global assessment of response to therapy . The secondary endpoints included the numeric pain rating for the first 14 days of treatment and the Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International ( OARSI ) responder rates . Results The WOMAC pain scores were reduced by approximately 50 % or more in all four groups . The 100 and 50 mg ketoprofen groups , but not the 25 mg group , showed a superior reduction in the WOMAC pain score versus the TDT 064 group ( 100 mg : −57.4 % [ P = 0.0383 ] ; 50 mg : −57.1 % [ P = 0.0204 ] ; and 25 mg : −53.4 % [ P = 0.3616 ] versus TDT 064 : −49.5 % ) . The superiority of the ketoprofen-containing formulations was not demonstrated for the WOMAC function subscale score , whereas the patient global assessment of 50 mg ketoprofen group , but not the 100 or 25 mg group , was superior to that of the TDT 064 group ( P = 0.0283 ) . Responder rates were significantly higher for all the IDEA-033 groups versus the TDT 064 group , but were high in all groups ( 100 mg : 88.6 % ; 50 mg : 86.8 % ; 25 mg : 88.6 % ; and TDT 064 : 77.5 % ) . Dermal reactions were the only relevant drug-related adverse events in all four groups . Conclusion The 50 and 100 mg ketoprofen doses of IDEA-033 were only marginally superior to TDT 064 for reducing pain associated with knee OA . The study indicates a high treatment response to the topical ketoprofen-free vehicle TDT 064 Objective . This r and omized , double-blind , phase III study evaluated the efficacy and safety of ketoprofen in an ultradeformable vesicle gel compared with ketoprofen-free gel in osteoarthritis ( OA ) knee pain . Methods . Patients with American College of Rheumatology-defined OA of the knee and moderate pain were r and omized to receive 100 mg ketoprofen in 4.4 g transfersome gel ( IDEA-033 ) or 4.4 g ketoprofen-free vehicle ( TDT 064 ) topically , twice daily , for 12 weeks . The primary endpoint was mean change in Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscale score from baseline to Week 12 . Results . Patients ( n = 555 ) were r and omized and treated .  Mean baseline WOMAC pain scores were 5.2 ( SD 1.0 ) for IDEA-033 and 5.3 ( SD 1.0 ) for TDT 064 . Mean change in WOMAC pain scores from baseline to Week 12 was 38.6 % for IDEA-033 and 44.6 % for TDT 064 ( Mann-Whitney estimator 0.4505 ; p = 0.022 ) . Both groups reported progressive decreases in pain and improvements in function and stiffness . Mean baseline WOMAC function scores decreased from 5.4 to 3.4 with IDEA-033 and 3.1 with TDT 064 at Week 12 . The proportion of patients achieving ≥ 50 % decrease in WOMAC pain score from baseline at Week 12 was 41.2 % ( 95 % CI 0.35–0.47 ) with IDEA-033 and 50.5 % ( 95 % CI 0.45–0.57 ) with TDT 064 . Mild skin and subcutaneous tissue disorders were the most frequently reported treatment-related adverse events ( AE ) . Conclusions . IDEA-033 was inferior to drug-free gel ( TDT 064 ) in relieving moderate OA knee pain and improving joint function ( Clinical Trials NCT00722852 ) The risk of oral NSAID including Cox-2 inhibitors to cause gastrointestinal , renal or cardiovascular adverse events related to systemic drug exposure could be reduced by local application . But only few long-term studies have been published to show safety and efficacy for long-term use of topical NSAID s. Diractin ( formerly IDEA-033 ) is a viscous , aqueous formulation for epicutaneous application of ketoprofen based on ultra-deformable , self-regulating carrier ( Transfersome ) . This multiple-dose , open label study with treatment periods up to 18 months included 402 patients with joint pain , musculoskeletal pain , stiffness or soft tissue inflammation ( age of 61.4+/-11.5 years ) . Most of the patients suffered from osteoarthritis ( OA ) of the knee ( 68.9 % ) .  Diractin was applied epicutaneously up to twice daily with a maximum dose of 220 mg ketoprofen per a maximum of 2 application sites . The mean pain score at baseline was 5.4+/-.4 on a 10 point categorical scale . During the study the pain score progressively improved up to week 36 ( 3.5+/-1.9 ) without a substantial further change during the rest of observation period of up to 18 months . The reduction of pain scores between week 0 ( baseline ) and at all later visits was statistically significant ( P<0.0001 ) . Patients also reported an improvement of quality of life on the EUROQoL. The majority of treatment related adverse events were skin and subcutaneous tissue disorders with the highest frequency reported for erythema ( 16.7 % ) and pruritus ( 2.0 % ) . Systemic ketoprofen exposure remained low throughout the study period with plasma concentrations of less than 1 % of what was reported for a single , st and ard oral dose of 200 mg ketoprofen . There were no occurrences of treatment related serious adverse events and no remarkable changes in laboratory values or vital signs . In summary , Diractin provided adequate pain relief with a good safety and tolerability profile when used for up to 18 months ( 72 weeks ) The clinical efficacy of the two topical analgesics , ketoprofen hydroalcoholic gel ( Fastum gel ) and diclofenac emulgel , for  osteoarthritis of the knee  was studied . There were 85 patients who underwent the trial . They were r and omly allocated into 2 groups , the diclofenac group , 42 patients ( 4 males and 38 females ) receiving the diclofenac emulgel at the painfull site four times a day for 4 weeks , and the ketoprofen group , 43 patients ( 9 males and 34 females ) receiving the ketoprofen hydroalcoholic gel four times a day for 4 weeks at the painful knee . Golberg 's knee scoring was used to evaluate the patients before the trial , at the end of the first , second and fourth weeks . The ketoprofen group had poorer a score before the trial , however , both groups had improvement in their knee functions , knee score and pain . There was no significant difference between the groups at the end of the study . There was no serious side effect in both groups . Ketoprofen hydroalcoholic gel gave persuasive results in the treatment of knee arthrosis stage I and II OBJECTIVE To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib . METHODS ; A multicentre , double-blind controlled study in which patients with knee OA and moderate pain were r and omized to one of the six arms : topical ketoprofen 50 or 100 mg in ultradeformable vesicles ( IDEA-033 ) , 2.2 or 4.4 g ketoprofen-free vehicle ( TDT 064 ) , oral celecoxib 100 mg or matching oral placebo , all bd . The primary outcome was change from baseline in the WOMAC pain subscale at week 12 . RESULTS A total of 1395 patients received treatment .  Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups . The mean reduction in WOMAC pain score at week 12 was -1.9 ( -40.8 % ) for ketoprofen 50 mg , -1.9 ( -40.9 % ) for ketoprofen 100 mg , -1.9 ( -39.8 % ) for 2.2 g TDT 064 , -1.8 ( -37.8 % ) for 4.4 g TDT 064 , -1.9 ( -40.4 % ) for celecoxib and -1.4 ( -29.3 % ) for oral placebo . IDEA-033 was not statistically superior to TDT 064 . All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib . The most frequent types of treatment-related adverse events reported were gastrointestinal for oral ( 15.9 % for celecoxib ) and dermal for topical applications ( 12.2 % for ketoprofen 100 mg ) . CONCLUSION IDEA-033 was not superior to ketoprofen-free vehicle , but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain . TRIAL REGISTRATION Clinical Trials.gov , http:// clinical trials.gov/ , NCT00716547 Objective : To compare epicutaneous ketoprofen in Transfersome ( ultra-deformable vesicles , IDEA-033 ) versus oral celecoxib and placebo for relief of signs and symptoms in  knee osteoarthritis  . Methods : This was a multicentre , r and omised , double-blind , controlled trial ; 397 patients with knee osteoarthritis participated and 324 completed the trial . They were r and omly assigned 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo ( n = 138 ) , 100 mg oral celecoxib plus placebo gel ( n = 132 ) , or both placebo formulations ( n = 127 ) twice daily for 6 weeks . Primary efficacy outcome measures were the changes from baseline to end of the study on the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index pain subscale , physical function subscale and patient global assessment ( PGA ) of response . Results : The mean WOMAC pain subscale scores in the intent to treat population were reduced by 18.2 ( 95 % confidence interval −22.1 to −14.3 ) , 20.3 ( −24.3 to −16.2 ) and 9.9 ( −13.9 to −5.8 ) in the IDEA-033 , celecoxib and placebo groups , respectively , and the physical function subscale score by 14.6 ( −18.1 to −11.0 ) , 16.6 ( −20.2 to −13.0 ) and 10.2 ( −13.8 to −6.6 ) , respectively . The mean PGA of response scores were 1.8 ( 1.6 to 2.1 ) , 1.7 ( 1.5 to 1.9 ) and 1.3 ( 1.1 to 1.5 ) , respectively . The differences in change between IDEA-033 and placebo were statistically significant for pain subscale ( p<0.01 ) and PGA of response ( p<0.01 ) . Gastrointestinal adverse events for IDEA-033 were similar to placebo . Conclusion : IDEA-033 is superior to placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis Objective To investigate the effect of epicutaneously applied Diractin ® ( ketoprofen in Transfersome ® gel ) on pain induced by eccentric muscle contractions . Methods Three pilot studies which were subsequently pooled for a meta- analysis compared the efficacy of a single application of 25 mg ketoprofen in Diractin ® to 25 mg oral ketoprofen and placebo for the treatment of pain induced by 50 eccentric contractions of the elbow flexor muscles . In addition , the effect of multiple usage of up to 100 mg ketoprofen in Diractin ® bid over seven days on pain induced by walking down stairs with a total altitude of 200 meters was investigated . Results A single dose of 25 mg ketoprofen in Diractin ® after the elbow flexion exercise was significantly superior to placebo from 5 to 12 hours after treatment and also to oral ketoprofen at some time points after treatment . In contrast , oral ketoprofen  was not different to placebo at any time after treatment . Multiple doses of up to 100 mg ketoprofen Diractin ® provided significant more pain relief than placebo on muscle pain induced by walking down stairs . Conclusions Eccentric exercise-induced muscle soreness was shown to be an appropriate acute pain model to evaluate the efficacy of nonsteroidal anti-inflammatory drugs applied epicutaneously with Transfersome ® carriers . Diractin ® proved to be efficacious in relieving pain from eccentric muscle contractions and muscle overexercise , respectively . The effect needs to be confirmed in a larger prospect i ve clinical trial In a r and omized , double blind , multicentre study with 4 weeks follow-up of 290 patients with osteoarthritis of the knee joint , a topical NSAID ( eltenac ) was compared with oral diclofenac and placebo . The main outcome , Lequesne 's Index and pain by VAS showed no statistically significant differences between neither of the active treatments and placebo for the total study population . However , in patients with more severe symptoms , both active groups showed statistically significant differences to placebo .  No severe adverse drug reactions were seen but the number of GI reactions were three times higher in the diclofenac group compared to the topical treatment . Local skin reactions were twice as frequent in the eltenac than in the placebo group . Taking into account the nature of the treatment for a chronic disease like OA , our results indicate that eltenac gel could be a safe alternative to oral NSAIDs OBJECTIVE We investigated the effects of celecoxib , diclofenac , and ibuprofen on the disease-specific quality of life , synovial fluid cytokines and signal transduction pathways in symptomatic knee osteoarthritis ( OA ) . DESIGN Ninety patients scheduled for a total knee arthroplasty ( TKA ) were r and omized to six groups that were treated with low and high dosages of celecoxib , diclofenac or ibuprofen . At the time of the first admission ( T0 ) and at surgery ( T1 = 14 days after beginning of the nonsteroidal anti-inflammatory drugs ( NSAIDs ) ) , sample s of knee synovial fluid were obtained from each patient for analysis . During the surgery the synovial tissue was harvested from the knee of patients . The Western Ontario and McMaster universities ( WOMAC ) score was used to evaluate the patient disease-specific quality of life at T0 and T1 . Microarray tests performed at T0 and T1 were used to evaluate the effects of NSAIDs on Tumor necrosis factor (TNF)-alpha , Interleukin-6 ( IL-6 ) , IL8 and Vascular endothelial growth factor ( VEGF ) concentration in the synovial fluid . Western blot assays evaluated the effects of NSAIDs on MAP kinase ( MAPK ) signal transduction pathway in the synovial membrane . RESULTS NSAID treatment induced a statistically significant improvement in the WOMAC score and a statistically significant decrease in the IL-6 , VEGF and TNF-alpha concentration in the synovial fluid . Higher dosages of NSAIDs provided a greater improvement in the disease-specific quality of life of patients and lower concentrations of pro-inflammatory cytokines in the synovial fluid . Inhibition of MAPKs was noted after NSAID treatment . CONCLUSION Short-term NSAID treatment improves the patient disease-specific quality of life with a parallel decrease in pro-inflammatory synovial fluid cytokine levels in knee OA . Signal transduction pathways may be involved in regulating the anti-inflammatory effects of NSAIDs . Clinical Trial.gov : NCT01860833 Osteoarthritis ( OA ) is a chronic degenerative joint disease that is debilitating for many individuals . While oral nonsteroidal anti-inflammatory drugs ( NSAIDs ) remain a common and effective treatment approach to managing OA , concerns over cardiovascular and gastrointestinal adverse events can potentially limit their use . Various formulations of topical NSAIDs have been shown to provide effective localized treatment with minimal adverse events . A patient perception study was conducted to evaluate patient preference between topical diclofenac sodium gel and that of diclofenac sodium topical solution with the penetration enhancer dimethyl sulfoxide ( DMSO ) .  Twenty-four healthy volunteers were r and omized and asked to administer one dose of the topical products . Surveys were provided and assessed immediately after application , 5 minutes after application , and after the application had dried to gauge subjects ' overall experience with the topical preparation . Overall , each drug 's application was well tolerated and no adverse events were reported . Results of the patient preference survey demonstrated that topical diclofenac solution with DMSO had a number of characteristics that were rated significantly better than for diclofenac sodium gel .  Mean subjective responses to topical diclofenac solution with DMSO  were also more favorable for most items in the question naire , and more subjects preferred or highly preferred topical diclofenac solution with DMSO over diclofenac sodium gel A parallel , double-blind , placebo controlled and r and omized study in a single center was done with ketoprofen 2.5 % gel to treat acute soft tissue injuries . Patients applied the gel twice a day for seven days , corresponding to 250 mg of ketoprofen per day . Assessment s were made on the third and seventh day by VAS , subjective evaluation and pain threshold algometry . The study group consisted of 29 patients and the control group 27 patients .  Pain at rest was significantly relieved in the ketoprofen group , whereas in the placebo group the difference was not significant . In terms of side-effects , no difference between the groups was noticed . In both groups , local dermal irritation was found . Our results suggested that ketoprofen 2.5 % gel was safe and superior to placebo in the treatment of soft tissue injuries Background Topical nonsteroidal anti-inflammatory drugs offer the advantage of enhanced drug delivery to local affected tissues with low plasma levels and an expected reduced incidence of systemic adverse events ( mainly peptic ulcer disease and gastrointestinal hemorrhage ) . Hypothesis To test the efficacy and tolerability of a 100-mg patch of ketoprofen applied once a day . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods The 2-week trial included patients suffering painful ( spontaneous pain ≥50 mm on a 0- to 100-mm visual analog scale ) , benign ( grade I or II ) , recent ( < 2 days ) ankle sprains as a model of general traumatic soft tissue injuries . The primary efficacy criterion was spontaneous pain change after 7 days of treatment in the intention-to-treat population . One hundred sixty-three patients were r and omized ( ketoprofen  , 81 ; placebo  , 82 ) . Results After 1 week of treatment , the decrease in spontaneous pain was -50 ± 20 mm for ketoprofen and -38 ± 24 mm for the placebo , showing a statistically significant intergroup difference ( P = . 0007 ) . The majority of the secondary criteria were also statistically significant in favor of the ketoprofen  patch . Tolerance was good in both groups , adverse events being mostly local . Conclusion This trial suggested that a 7-day course of treatment with a ketoprofen patch is useful in benign ankle sprain , without revealing unexpected adverse events BACKGROUND Orally administrated nonsteroidal anti-inflammatory drugs are effective in the treatment of a variety of acute and chronic pain conditions but their use may be associated with serious systemic adverse effects which are correlated with the therapeutic plasma levels of the drug . In order to minimize the incidence of drug related systemic events , topical formulations of the nonsteroidal anti-inflammatory drugs have been developed . A recently performed review of the evidence from r and omized , double-blind , placebo controlled trials with topically applied NSAIDs in the treatment of acute pain confirmed the previously described pain relief effectiveness . For all topical nonsteroidal anti-inflammatory drugs combined , in comparison to placebo , the number needed to treat ( NNT ) to achieve a clinical ly meaningful pain relief of 50 % was 4.5 ( 3.9 to 5.3 ) for treatment periods of 6 to 14 days . Local skin reactions were generally mild and transient , and did not differ from placebo . OBJECTIVES The present is an observational , multicenter , open-label , non-interventional , post-authorization safety study as it is defined by Article 21 of the European Clinical Trials Directive 2001/20/EC . The main objective of this study was to evaluate the local tolerability and the therapeutic efficacy of static and pain on movement intensity reduction of Ketospray ® 10 % cutaneous spray solution administered in accordance with the terms of the marketing authorization and last version of summary of product characteristics approved by National Medicines Agency of Romania . METHODS In compliance with the Post-marketing study type , the assignment of the patient to a particular therapeutic strategy fell within current practice . The prescription of the medicine was not subject to compliance with predefined patients ' characteristics . No specific , out of the daily practice routine diagnostic , monitoring , instrumental or laboratory assessment s were foreseen by the study protocol . Patients ' data were collected into respective case report forms . Study medication , Ketoprofen 10 % Cutaneous Spray Solution was administered to the affected area at the dose of 3 - 6 spray puffs , 2 - 3 times a day , for 7 days . According to the study type , descriptive statistical methods were applied . Since almost half of the patients were treated with combination of the pain relieving medications , sizing of the pain relieving effects , as NNT , between the two groups was made . FINDINGS There were 2020 study subjects in safety and ITT analysis population and 1802 ( 89 % ) in PP efficacy analysis population . There were 4 types of injuries : non-complicated strain-sprain ( 555 ) , soft tissue contusion ( 323 ) , low back pain ( 461 ) and osteoarthritis ( 681 patients ) . Ten patients reported 13 side effects of which 10 were recognized by investigators as adverse drug reactions . All side effects were non-serious , listed , application site skin changes . Remarkable reductions of static and pain on movement intensity were experienced by patients irrespective of the type of the injury and the type of the treatment . However , a clinical ly meaningful benefit of the concomitantly prescribed pain relieving medications was not observed for any type of pain . The lowest NNT ( 14 ) was obtained for the reduction of pain at rest in patients with strain-sprain or soft tissue contusions . The highest NNT ( 283 ) was for pain at rest in patients treated for the exacerbation of the chronic pain . CONCLUSIONS The results of the current post-authorization study confirm beneficial pain intensity reducing efficacy of Ketospray 10 % associated with good local tolerability of 7 days treatment course . Concomitant administration of systemic pain relieving medication did not substantially contribute neither to the relief of pain at rest nor of pain on movement among the subjects of respective study population 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 , r and omized , double-blind , parallel-group , multicentre trials . Setting : US primary care , internal medicine , orthopaedic and rheumatology practice s. 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 sub population [ 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 [ st and ard 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 . Clinical trials.gov registration numbers NCT00171626 , NCT00171678 , NCT00426621 BACKGROUND Oral nonsteroidal anti-inflammatory drugs ( NSAIDs ) are commonly used to relieve the symptoms of osteoarthritis ( OA ) but can produce harmful systemic effects and end-organ damage . A topical NSAID formulation may provide symptom relief with fewer adverse effects . A new topical diclofenac sodium solution-containing the absorption enhancer dimethyl sulfoxide-was evaluated for the relief of the symptoms of primary OA of the knee . METHODS A total of 326 patients met entry criteria ( including abnormal radiographic findings and flare of pain ) and were r and omized to receive 40 drops of topical diclofenac solution or a vehicle-control solution , 4 times daily , for 12 weeks . We evaluated 3 primary outcome measures , the Western Ontario McMaster Universities LK3.1 OA Index ( WOMAC ) pain and physical function subscales and a patient global assessment , and 2 other measures , stiffness and pain on walking , at baseline and after final application . We assessed safety by evaluation of adverse events , vital signs , and irritation at the application site . RESULTS Topical diclofenac solution was significantly more effective than the vehicle-control solution for all outcome measures ; pain , P = .001 ; physical function , P = .002 ; patient global assessment , P = .003 ; stiffness , P = .005 ; and pain on walking , P = .004 . Among patients receiving topical diclofenac , self-limiting minor skin irritation occurred in 68 ( 41.5 % ) of 164 patients , including dryness in 60 ( 36.6 % ) , rash in 18 ( 11.0 % ) , and paresthesia , pruritus , and vesiculobullous rash in 1 ( 0.6 % ) each . There was no significant difference between groups in NSAID-related gastrointestinal tract complaints or in dropouts due to study -related adverse effects . CONCLUSION Topical diclofenac is effective in the treatment of the symptoms of primary OA of the knee , with only minor local irritation and no significant systemic adverse events OBJECTIVES Nonsteroidal anti-inflammatory drugs have dose-related adverse effects . Topical nonsteroidal anti-inflammatory drugs may offer local efficacy with low systemic drug levels . This study assessed the efficacy and safety of topical diclofenac sodium 1 % gel ( DSG ) in mild to moderate symptomatic knee osteoarthritis . METHODS In a r and omized , double-blind , vehicle-controlled trial , 492 adults aged > or=35 years with symptomatic knee osteoarthritis of > or=6 months ' duration were r and omized to DSG 4 g ( n = 254 ) or vehicle ( n = 238 ) 4 times daily for 12 weeks . Primary efficacy outcomes at week 12 were the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscale , WOMAC physical function subscale , and global rating of disease . Secondary outcomes included these outcomes assessed after 1 , 4 , and 8 weeks , and pain on movement assessed using a 100-mm visual analog scale . All adverse events were recorded . RESULTS At week 12 , the DSG group had significant decreases versus the vehicle group in mean WOMAC pain ( P = 0.01 ) , mean WOMAC physical function ( P = 0.001 ) , and mean global rating of disease ( P < 0.001 ) . Efficacy outcomes significantly favored DSG versus vehicle beginning at week 1 . Application site reactions occurred in 5.1 % and 2.5 % of patients in the DSG and vehicle groups , respectively . The incidence of gastrointestinal disorders was 5.9 % with DSG and 5.0 % with vehicle . CONCLUSIONS Over a 3-month treatment period , topical treatment with DSG achieved statistically and clinical ly significant improvements of pain and measures of physical function in patients with knee osteoarthritis Topical application , 4 times daily for 2 weeks , of the diclofenac-hyaluronan gel to 59 osteoarthritis patients induced a significantly greater ( p = 0.057 ) analgesic effect than placebo gel lacking the active substance applied to 60 control patients
All topical ketoprofen in Transfersome gel groups ( 25 mg , 50 mg and 100 mg ) had improvements in pain that were superior to all other treatment arms , and the 50 mg topical ketoprofen in Transfersome gel group had functional gains that were superior to all other treatment arms .
The majority of the adverse events were non-serious and related to skin and subcutaneous tissue disorders , with erythema being the most common .
Topical ketoprofen in Transfersome gel is an effective means of treating symptoms of knee OA , and is superior to oral celecoxib , oral placebo and topical placebo .
The most commonly reported adverse events associated with the use of topical ketoprofen in Transfersome gel were non-severe skin and subcutaneous tissue disorders .
Furthermore , as topical ketoprofen in Transfersome gel was associated with fewer adverse events when compared with oral celecoxib , and had rates of GI adverse events comparable with those of topical placebo , it may be ideal for those who are unable to take oral NSAIDs
PURPOSE Topical ketoprofen in Transfersome gel has been used for the alleviation of symptoms in osteoarthritis .
Non-steroidal anti-inflammatory drugs ( NSAIDs ) are associated with various side effects .
Topical NSAIDs are known to have a lower side-effect profile when compared with systemic administration .
The present systematic review aim ed to determine the safety and efficacy of topical ketoprofen in Transfersome gel in knee osteoarthritis ( OA ) .