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 Efficacy and safety of eltenac gel in the treatment of knee osteoarthritis. A comparative subjective assessment study of PENNSAID® and Voltaren Gel®, two topical formulations of diclofenac sodium. Topical nonsteroidal anti-inflammatory drugs versus oil of evening primrose in the treatment of mastalgia. 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. A Pilot Double-Blinded, Randomized, Clinical Trial of Topical Virgin Olive Oil Versus Piroxicam Gel in Osteoarthritis of the Knee Diclofenac topical solution compared with oral diclofenac: a pooled safety analysis The symptomatic effects of intra-articular administration of hylan G-F 20 on osteoarthritis of the hip: clinical data of 6 months follow-up A comparison of ketoprofen SR and sulindac in the elderly with rheumatoid arthritis. Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study Efficacy of S-flurbiprofen plaster in knee osteoarthritis treatment: Results from a phase III, randomized, active-controlled, adequate, and well-controlled trial Efficacy of symptomatic control of knee osteoarthritis with 0.0125% of capsaicin versus placebo. Local tolerability and effectiveness of Ketospray® 10% cutaneous spray solution.
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 OBJECTIVE A double-blind , placebo-controlled dose-finding study was performed in 237 patients with predominantly unilateral knee osteoarthritis ( OA ) evaluating efficacy and safety  of a new topical NSAID . DESIGN The patients applied 3 g tid eltenac gel 0.1 % , 0.3 % , 1 % or placebo gel over a period of 4 weeks . The patients were supplied with paracetamol tablets as an escape analgesic . Primary efficacy end-point was mean global pain in the week preceding the examinatio ns , evaluated on a visual analog scale ( VAS ) . Secondary criteria were Lequesne 's score ISK , Jezek score , muscle strength and dolorimeter measurements , walking time , clinical examination results of the knee joint and patient 's and investigator 's overall efficacy estimates . RESULTS The graphical depiction of VAS and ISK suggested a dose-related efficacy , but the pre-planned statistical analysis did not show significant differences between treatments . In the patient subgroup with a higher degree of baseline severity of knee OA the ISK showed significant and relevant advantages of eltenac gel 1 % to placebo at different examination times . Two patients each of the eltenac gel 1 % group and the placebo group showed local intolerance reactions which subsided spontaneously . CONCLUSION This study did not provide confirmatory proof of an efficacy of topical eltenac in patients with knee OA . Method ological pitfalls and possible responder subgroups are described . Despite the difficulties , dose-finding studies seem to be feasible even with topical NSAIDs 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 OBJECTIVE To compare oil of evening primrose ( OEP ) and topical nonsteroidal anti-inflammatory ( NSAIDs ) with respect to safety , effectiveness , rapidity of response , cost effectiveness and acceptability in the treatment of breast pain . STUDY DESIGN An open , non-r and omised , comparative study of topical ( NSAI ) gel versus OEP was carried out , over a period of one year . PATIENTS AND METHODS Fifty female patients attending the outpatient department with moderate to severe breast pain were given one of the two agents alternatively , after selection . RESULTS Results showed that out of 25 patients treated with OEP , 64 % had a clinical ly significant response after three months of treatment , compared with 92 % with topical NSAIDs . Only one patient ( 4 % ) had side effects with OEP , while no patient had side effects with topical NSAIDs . Twenty per cent and seventy per cent showed acceptability as far as costs were concerned and mode of administration respectively , with OEP . The acceptability rate was 68 % and 96 % respectively , with topical NSAIDs . CONCLUSION This study has shown topical NSAIDs to be safe , effective , rapid and acceptable mode of treatment for cyclical and non-cyclical mastalgia 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 O steoarthritis ( OA ) is the most common type of arthritis , and the knee is the most common site of symptomatic OA . Knee OA is responsible for a higher incidence of disability than any other long-term conditions . Topical therapies present a therapeutic option for OA pain management .  Nonsteroidal antiinflammatory drugs ( NSAIDs ) , salicylates , and capsaicin are currently the main topical therapies available . There is a need for safe and effective drugs for patients who do not respond well to conventional medical therapy . Indeed , such patients are turning increasingly to complementary/alternative medicines . One of the traditional methods for management of knee pain in some rural area of Iran is application of topical olive oil , as reported by Avicenna in his 10th-century book Canon of Medicine . Although the composition of olive oil is complex , the major groups of compounds thought to contribute to its observed health benefits include oleic acid , phenolics , and squalene , all of which have been reported to inhibit oxidative stress . Research ers reported beneficial effects of olive oil on rheumatoid arthritis after oral consumption . In 2005 , (j)-oleocanthal , the dialdehydic form of (j)-deacetoxy-ligstroside aglycone present in freshly pressed extra virgin olive oil , was shown to have properties of an NSAID . Although topical virgin olive oil is traditionally used in Iran in treating knee pain as an herbal medication , our survey did not find any scientific evaluation of its efficacy . Accordingly , we conducted a pilot prospect i ve , comparative , r and omized , doubleblinded trial of topical virgin olive oil therapy versus piroxicam gel in the treatment of knee OA . The report was prepared as recommended by the CONSORT statement and its elaboration on herbal interventions Background Topical nonsteroidal anti-inflammatory drug ( NSAID ) formulations , which produce less systemic exposure compared with oral formulations , are an option for the management of osteoarthritis ( OA ) . However , the overall safety and efficacy of these agents compared with oral or systemic therapy remains controversial . Methods Two 12-week , double-blind , double-dummy , r and omized , controlled , multicenter studies compared the safety and efficacy profiles of diclofenac topical solution ( TDiclo ) with oral diclofenac ( ODiclo ) . Each study independently showed that TDiclo had similar efficacy to ODiclo . To compare the safety profiles of TDiclo and ODiclo , a pooled safety analysis was performed for 927 total patients who had radiologically confirmed symptomatic OA of the knee . This pooled analysis included patients treated with TDiclo , containing 45.5 % dimethyl sulfoxide ( DMSO ) , and those treated with ODiclo . Safety assessment s included monitoring of adverse events ( AEs ) , recording of vital signs , dermatologic evaluation of the study knee , and clinical laboratory evaluation . Results AEs occurred in 312 ( 67.1 % ) patients using  TDiclo  versus 298 ( 64.5 % ) of those taking ODiclo . The most common AE with TDiclo  was dry skin at the application site ( 24.1 % vs 1.9 % with ODiclo ; P < 0.0001 ) . Fewer gastrointestinal ( 25.4 % vs 39.0 % ; P < 0.0001 ) and cardiovascular ( 1.5 % vs 3.5 % ; P = 0.055 ) AEs occurred with TDiclo compared with ODiclo . ODiclo was associated with significantly greater increases in liver enzymes and creatinine , and greater decreases in creatinine clearance and hemoglobin ( P < 0.001 for all ) . Conclusions These findings suggest that TDiclo represents a useful alternative to oral NSAID therapy in the management of OA , with a more favorable safety profile Hip osteoarthritis ( OA ) is usually managed with systemic treatments such as nonsteroidal anti-inflammatory drugs ( NSAIDs ) and /or symptomatic slow-acting drugs . Unfortunately , many patients either can not tolerate NSAIDs or suffer serious , even fatal , NSAID-induced side effects , predominantly gastrointestinal ulceration and bleeding . Viscosupplementation , which aims to restore physiological and rheological features of the synovial fluid , is a well-accepted therapeutic option in knee OA patients , but limited data exist in the literature about its potential benefit for the treatment of hip OA . The purpose of this study is to observe the effects of hylan G-F 20 administered through ultrasound (US)-guided intra-articular ( IA ) injections in patients with symptomatic hip OA . We treated 30 patients with symptomatic hip OA . Under US guidance , 7 patients received one injection , 21 patients had two injections , and 2 patients received three injections , each with 2 ml of hylan G-F 20 .  Lequesne index , VAS scale of hip pain , and NSAID consumption were evaluated at baseline as well as 2 and 6 months after the beginning of the treatment . No systemic adverse events were observed . Lequesne index , VAS pain score , and NSAID consumption showed a reduction that was statistically significant to the baseline . The present observation suggests the potentiality for the safety and efficacy of hylan G-F 20 injected under US guidance in patients with symptomatic hip OA . Further controlled studies are needed The elderly ( age > 65 years ) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs ( NSAIDs ) . We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis , 65 years of age or older .  Sulindac was chosen because of its possible renal sparing effects , and ketoprofen SR because of its short half life and sustained release delivery system . Eighty patients were entered . More patients withdrew from the study due to side-effects in the sulindac group ; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs , demonstrating that the elderly are susceptible to side-effects from NSAIDs Objective To determine whether older patients with chronic knee pain should be advised to use topical or oral non-steroidal anti-inflammatory drugs ( NSAIDs ) . Design R and omised controlled trial and patient preference study . Setting 26 general practice s. Participants People aged ≥50 with knee pain : 282 in r and omised trial and 303 in preference study . Interventions Advice to use topical or oral ibuprofen . Primary outcome measures WOMAC ( Western Ontario and McMaster Universities ) osteoarthritis index , major and minor adverse effects . Results Changes in global WOMAC scores at 12 months were equivalent . In the r and omised trial the difference ( topical minus oral ) was two points ( 95 % confidence interval −2 to 6 ) ; in the preference study , it was one point ( −4 to 6 ) . There were no differences in major adverse effects in the trial or study . The only significant differences in secondary outcomes were in the r and omised trial . The oral group had more respiratory adverse effects ( 17 % v 7%,95 % confidence interval for difference −17 % to −2 % ) , the change in serum creatinine was 3.7 mmol/l less favourable ( 0.9 µmol/l to 6.5 µmol/l ) ; and more participants changed treatments because of adverse effects ( 16 % v 1 % , −16 % to −5 % ) . In the topical group more participants had chronic pain grade III or IV at three months , and more participants changed treatment because of ineffectiveness . Conclusions Advice to use oral or topical preparations has an equivalent effect on knee pain over one year , and there are more minor side effects with oral NSAIDs . Topical NSAIDs may be a useful alternative to oral NSAIDs . Trial registration IS RCT N 79353052 Objectives : S-flurbiprofen plaster ( SFPP ) is a novel non-steroidal anti-inflammatory drug ( NSAID ) patch , intended for topical treatment for musculoskeletal diseases . This trial was conducted to examine the effectiveness of SFPP using active comparator , flurbiprofen ( FP ) patch , on knee osteoarthritis ( OA ) symptoms . Methods : This was a phase III , multi-center , r and omized , adequate , and well-controlled trial , both investigators and patients were blinded to the assigned treatment . Enrolled 633 knee OA patients were treated with either SFPP or FP patch for two weeks . The primary endpoint was improvement in knee pain on rising from the chair as assessed by visual analogue scale ( rVAS ) . Safety was evaluated through adverse events ( AEs ) . Results : The change in rVAS was 40.9 mm in SFPP group and 30.6 mm in FP patch group ( p < 0.001 ) . The incidence of drug-related AEs at the application site was 9.5 % ( 32 AEs , 29 mild and 3 moderate ) in SFPP and 1.6 % in FP patch ( p < 0.001 ) . Withdrawals due to AE were five in SFPP and one in FP patch . Conclusions : The superiority of SFPP in efficacy was demonstrated . Most of AEs were mild and few AEs led to treatment discontinuation . Therefore , SFPP provides an additional option for knee OA therapy BACKGROUND Knee osteoarthritis ( OA ) is prevalent and associated with both pain and functional disability . Current treatments aim to alleviate mild to moderate symptoms by various methods . Topical capsaicin ( 0.075 % and 0.05 % ) has been evaluated for the treatment of the painful joints . A burning sensation was the most common side effect at these strengths . Therefore , the authors aim ed to evaluate the efficacy of 0.0125 % capsaicin gel ( Capsika gel ) compared to a placebo ( the vehicle gel ) in patients with symptomatic OA knee . MATERIAL AND METHOD This was a cross-over ; double blinded , r and omized , controlled trial of 100 patients with mild to moderate knee OA . All of the patients received either capsaicin gel or placebo gel applied to the affected knee , three times daily for 4 weeks with one week washout period after which the treatment switched to either capsaicin gel or placebo gel for the next 4 weeks . A blinded examiner used the visual analog scale ( VAS ) and WOMAC score to do weekly assessment s. RESULTS Subjects averaged 61 years of age ( range , 44 to 82 ) . During the enrollment phase , only female farmers presented . Mean body weight and height was 62.97 + /- 10.25 kg and 1.54 + /- 0.053 m , respectively The respective baseline VAS and WOMAC score was 6.40 + /- 1.64 and 51.65 + /- 13.3 . The severity of OA , according to the KL criteria was : 83 patients with grade 2 and 16 with grade 3 . The respective mean difference of VAS and total WOMAC score in the capsaicin group vs. the placebo group was statistically significant ( p < 0.05 ) . The mean difference of the WOMAC pain , stiffness and functional subscales in the capsaicin vs. the placebo group was also significant ( p < 0.05 ) . The only adverse event reported was a burning sensation . During the 4-week treatment with capsaicin , approximately 67 % of patients had a burning sensation but none withdrew for this reason . CONCLUSION 0.0125 % capsaicin gel was an effective treatment in mildly to moderately painful OA knees . The burning sensation reported by patients in the capsaicin group was less disturbing than in previous studies and none of the present patients withdrew for this reason 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
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 ) .