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. 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 diclofenac sodium 2% topical solution for osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled, 4 week study Topical analgesics for knee arthrosis: a parallel study of ketoprofen gel and diclofenac emulgel. Effectiveness of topical non-steroidal anti-inflammatory drugs in the management of breast pain. 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 and Safety of Topical Nimesulide in the Treatment of Knee Osteoarthritis Local NSAID gel (eltenac) in the treatment of osteoarthritis of the knee. A double blind study comparing eltenac with oral diclofenac and placebo gel. Efficacy of epicutaneous Diractin® (ketoprofen in Transfersome® gel) for the treatment of pain related to eccentric muscle contractions
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 ) 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 Abstract Objective : Nonsteroidal anti-inflammatory drugs ( NSAIDs ) are st and ard therapy for osteoarthritis ( OA ) . Topically applied NSAIDs reduce systemic exposure compared with oral NSAIDS , and European guidelines recommend their use . The NSAID diclofenac is available in a range of topical formulations . Diclofenac 1 % gel and 1.5 % four times daily and 2 % twice daily ( BID ) solutions are approved to reduce pain from OA of the knee(s ) . The objective of this study was to investigate the efficacy and safety of diclofenac sodium 2 % topical solution BID versus vehicle control solution for treating pain associated with OA of the knee . Research design and methods : A phase II , 4 week , r and omized , double-blind , parallel-group , two-arm , vehicle-controlled study compared pain relief with diclofenac sodium 2 % topical solution versus control ( vehicle only ) in patients aged 40 to 85 years with radiographically confirmed primary OA of the knee . Clinical trial registration : Clinical Trials.gov identifier NCT01119898 . Main outcome measures : The primary efficacy outcome was change from baseline to the final visit in the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscale . Secondary outcomes included additional WOMAC subscales and patient global assessment of OA . Treatment-emergent adverse events ( TEAEs ) , skin irritation , and vital signs were assessed and collected throughout the study . Results : Of 260 patients r and omized , 259 received ≥1 dose of study drug . Significantly greater reductions in least-squares mean ( st and ard error ) WOMAC pain scores were observed for diclofenac-treated ( −4.4 [ 0.4 ] ) versus vehicle-treated patients ( −3.4 [ 0.4 ] ) at the final visit ( p = 0.040 ) . The most commonly reported TEAEs were administration site conditions . The vehicle-treated group experienced slightly more TEAEs than the active treatment group ( 38.8 % vs. 31.5 % ) . No serious adverse events were reported . Conclusions : Administration of diclofenac sodium 2 % topical solution BID result ed in significantly greater improvement in pain reduction in patients with OA of the knee versus vehicle control and was generally well tolerated 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 A prospect i ve study of the effectiveness of the topical application of non-steroidal anti-inflammatory drugs ( NSAIDs ) as a gel preparation was carried out in 26 women with severe breast pain . The results showed a satisfactory relief of pain in 81 % of the women : 11 of 13 with cyclical pain , eight of 11 with non-cyclical pain , and in two women with severe scar pain after lumpectomy and radiotherapy .  Topical NSAID gel was applied as required ; the relief of severe pain was rapid and no side effects were reported . These factors compare favourably with established recommended treatments which usually involve months of continuous treatment , tailoring of drug dosages and a significant incidence of intolerable side effects . This study has shown that topical NSAID application is an effective , safe , acceptable and easily administered treatment for severe cyclical and non-cyclical breast pain 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 Background : Osteoarthritis ( OA ) affects mainly older people who are more sensitive to adverse effects of classic nonsteroidal anti-inflammatory drugs . Recent publications indicate that topically applied nonsteroidal anti-inflammatory drugs are effective and much safer than their oral analogues . Objectives : In this double-blind , r and omized , placebo-controlled study design , we aim ed to investigate whether topical nimesulide treatment has any beneficial effect in knee OA patients . Methods : Seventy-four adult knee OA out patients were enrolled . We used Western Ontario and McMaster Universities OA Index ( WOMAC ) , Nottingham Health Profile ( NHP ) , and patient and physician global satisfaction scores . WOMAC and NHP scores were measured at the initial and final visit . Treatment group received topical nimesulide gel 1 % on the knee skin 3 times a day whereas placebo group received an identical-appearing gel for 30 days . Results : There was a significant improvement in the nimesulide treatment group for all 3 parameters and overall score of WOMAC between pretreatment and posttreatment values . The overall WOMAC scores was significantly better than placebo ( P = 0.03 ) , but physical functioning , stiffness , and pain scales did not reach statistical significance . For the NHP scores there was an improvement at “ energy level , ” “ pain , ” “ physical motion , ” and “ NHP distress ” scores in the treatment group whereas no improvement was found in the placebo group . Between-group differences were not significant . Both patient and physician satisfaction scores were significantly better in the treatment group . Conclusion : This study shows that topical nimesulide gel can have beneficial effects and can improve quality of life in patients with knee OA 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 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
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 ) .