Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study Steroids in duchenne muscular dystrophy — Deflazacort trial Deflazacort vs. prednisone in Duchenne muscular dystrophy: trends of an ongoing study Deflazacort in Duchenne dystrophy: study of long-term effect. A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group. A comparison of daily and alternate-day prednisone therapy in the treatment of Duchenne muscular dystrophy.
Objective : We aim ed to perform an observational study of age at loss of independent ambulation ( LoA  ) and side-effect profiles associated with different glucocorticoid corticosteroid ( GC ) regimens in Duchenne muscular dystrophy ( DMD ) . Methods : We studied 340 participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study ( CINRG-DNHS ) . LoA was defined as continuous wheelchair use . Effects of prednisone or prednisolone (PRED)/deflazacort ( DFZ ) , administration frequency , and dose were analyzed by time-varying Cox regression . Side-effect frequencies were compared using χ2 test . Results : Participants treated ≥1 year while ambulatory ( n = 252/340 ) showed a 3-year median delay in LoA ( p < 0.001 ) . Fourteen different regimens were observed . Nondaily treatment was common for PRED ( 37 % ) and rare for DFZ ( 3 % ) . DFZ was associated with later LoA than PRED ( hazard ratio 0.294 ± 0.053 vs 0.490 ± 0.08 , p = 0.003 ; 2-year difference in median LoA with daily administration , p < 0.001 ) . Average dose was lower for daily PRED ( 0.56 mg/kg/d , 75 % of recommended ) than daily DFZ ( 0.75 mg/kg/d , 83 % of recommended , p < 0.001 ) . DFZ showed higher frequencies of growth delay ( p < 0.001 ) , cushingoid appearance ( p = 0.002 ) , and cataracts ( p < 0.001 ) , but not weight gain . Conclusions : Use of DFZ was associated with later LoA and increased frequency of side effects . Differences in st and ards of care and dosing complicate interpretation of this finding , but stratification by PRED/DFZ might be considered in clinical trials . This study emphasizes the necessity of a r and omized , blinded trial of GC regimens in DMD . Classification of evidence : This study provides Class IV evidence that GCs are effective in delaying LoA in patients with DMD We conducted a double blind controlled trial in 28 Duchenne muscular dystrophy ( DMD ) patients with Deflazacort ( DF ) , an oxazoline derivative of prednisolone which reduces its side-effects . Myometric muscle strength measurements , Scott Score and timed tests showed statistically significant improvement for the treated group ( P less than 0.05 ) . Side-effects after 9 months of treatment included mild cushingoid appearance in four patients ( 28 % ) and moderate in only one ( 7 % ) , increased appetite in seven ( 50 % ) , increased body hair in four ( 28 % ) , irritability and hyperactivity in three ( 21 % ) . Increased body weight was not prominent and was controlled with dietary measures . No patient had to be withdrawn from medication . More research and long-term follow-up are needed in order to establish the mechanism of improvement and the consequences of long-term steroid administration in DMD . In this regard DF appears as an alternative to prednisone preserving its benefits but with fewer side-effects Several studies have demonstrated the slowing effect of corticosteroids on the decline of muscle strength in Duchenne muscular dystrophy ( DMD ) .  Deflazacort ( DFC ) is supposed to have fewer side effects than prednisone ( PRED ) . An ongoing double blind multicenter study is comparing the effects and side effects of deflazacort ( 0.9 mg/kg/day ) and prednisone ( 0.75 mg/kg/day ) in DMD . This interim report includes data for 67 boys between age 5 years and loss of ambulation . Besides the common clinical and laboratory data for chronic corticoid treatment , motor performance has been tested . Interim results , 3 - 15 months after starting the medication , show some scattering but no grouping of data for all the functions tested : timed motor functions , sum of the strength of 20 muscles according to a 10-point scale on manual testing , weight gain , osteocalcin and alkaline phosphatase . Only the changes in CK activity after 3 months medication might reflect two equal groups without any correlation with the initial activity or with other parameters . On average , there was no clear-cut loss of muscle strength or performance . Except for in 4 patients , who were excluded due to unacceptable weight gain and /or loss of ambulation  , there were no side effects considered to be serious . The results suggest that ( i ) DFC and PRED in equal anti-inflammatory dosage are similarly or equally efficient in slowing down the decline of muscle strength in DMD ; ( ii ) benefits outweigh the side effects . This allows the study to continue as design ed A r and omized double-blind controlled trial of deflazacort was conducted in 28 Duchenne muscular dystrophy patients either treated with deflazacort 2.0 mg/kg alternate-day therapy or placebo .  The deflazacort group showed significant improvement in climbing stairs ( P < 0.01 ) , in rising from a chair , Gower 's maneuver , and walking ( P < 0.0025 ) after 6 months of treatment . After 1 year , all the above changes remained significantly improved and the MRC index was significantly better ( P < 0.05 ) in the treated group . After 2 years , a significant change was found in the MRC index : higher scores in walking , chair rising ( P < 0.02 ) , and grade and time of Gower 's maneuver ( P < 0.05 ) were found . The mean time for loss of ambulation for the treated group after we started the trial was 33.2 + /- 9 months ; for the placebo group it was 20.5 + /- 11 months ( deflazacort vs. placebo group , P < 0.05 ) [ corrected ] . Our treated patients lost their ambulation at a median age of 11.8 years vs. 10.5 years in the placebo group . Side effects were mild , consisting of moderate weight gain and slight behavioral changes We r and omized 18 Duchenne muscular dystrophy ( DMD ) boys whose age ranged from 5.2 to 14.6 years ( mean , 7.3 years ) for treatment with either deflazacort ( 0.9 mg/kg/day ) or prednisone ( 0.75 mg/kg/day ) on the basis of age and functional score at the onset of treatment . We followed the patients every 3 months for 1 year , evaluating four limb muscles with the Medical Research Council scale and performance of four functions ( walking , climbing stairs , Gowers ' maneuver , and rising from a chair ) . Side effects were monitored by a question naire and by routine blood examination , and weight and height were recorded at each visit . At 12 months , the effect of both steroids was examined by comparing the status of the treated patients with another group of untreated DMD patients that served as natural history control . The two steroids were equally effective in improving motor function and functional performances . At 9 months , the average weight increase with respect to baseline value was 5 % ( 2 kg ) in the deflazacort group but 18 % in the prednisone group ( P < 0 . 005 ) , and the change remained significant after 12 months ( P < 0.05 ) . Other minor but nonsignificant side effects were observed . Steroid treatment with deflazacort appears to cause fewer side effects than with prednisone , particularly weight gain , which could be important to maximize motor performances BACKGROUND Glucocorticoid treatment is recommended as a st and ard of care in Duchenne muscular dystrophy ; however , few studies have assessed the long-term benefits of this treatment . We examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in patients with Duchenne muscular dystrophy . METHODS For this prospect i ve cohort study , we enrolled male patients aged 2 - 28 years with Duchenne muscular dystrophy at 20 centres in nine countries . Patients were followed up for 10 years . We compared no glucocorticoid treatment or cumulative treatment duration of less than 1 month versus treatment of 1 year or longer with regard to progression of nine disease-related and clinical ly meaningful mobility and upper limb milestones . We used Kaplan-Meier analyses to compare glucocorticoid treatment groups for time to st and from supine of 5 s or longer and 10 s or longer , and loss of st and from supine , four-stair climb , ambulation , full overhead reach , h and -to-mouth function , and h and function . Risk of death was also assessed . This study is registered with Clinical Trials.gov , number NCT00468832 . FINDINGS 440 patients were enrolled during two recruitment periods ( 2006 - 09 and 2012 - 16 ) . Time to all disease progression milestone events was significantly longer in patients treated with glucocorticoids for 1 year or longer than in patients treated for less than 1 month or never treated ( log-rank p<0·0001 ) . Glucocorticoid treatment for 1 year or longer was associated with increased median age at loss of mobility milestones by 2·1 - 4·4 years and upper limb milestones by 2·8 - 8·0 years compared with treatment for less than 1 month . Deflazacort was associated with increased median age at loss of three milestones by 2·1 - 2·7 years in comparison with prednisone or prednisolone ( log-rank p<0·012 ) . 45 patients died during the 10-year follow-up . 39 ( 87 % ) of these deaths were attributable to Duchenne-related causes in patients with known duration of glucocorticoids usage . 28 ( 9 % ) deaths occurred in 311 patients treated with glucocorticoids for 1 year or longer compared with 11 ( 19 % ) deaths in 58 patients with no history of glucocorticoid use ( odds ratio 0·47 , 95 % CI 0·22 - 1·00 ; p=0·0501 ) . INTERPRETATION In patients with Duchenne muscular dystrophy , glucocorticoid treatment is associated with reduced risk of losing clinical ly meaningful mobility and upper limb disease progression milestones across the lifespan as well as reduced risk of death . FUNDING US Department of Education/National Institute on Disability and Rehabilitation Research ; US Department of Defense ; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases ; and Parent Project Muscular Dystrophy A r and omized , controlled trial of daily prednisone was conducted in 99 boys ( aged 5 to 15 years ) with Duchenne dystrophy to define the time course of improvement and the dose response to treatment . Prednisone at 0.3 mg/kg ( n = 33 ) , prednisone at 0.75 mg/kg ( n = 34 ) , and placebo ( n = 32 ) were administered for 6 months . Patients were examined using manual muscle and myometry testing , timed functional testing , pulmonary function testing , and laboratory measurements at 10 days , 1 month , 2 months , 3 months , and 6 months of treatment . Boys treated with prednisone had stronger average muscle strength scores , than did boys treated with placebo as early as 10 days after starting therapy . At the 3-month visit , the boys in the group given 0.75 mg/kg of prednisone were significantly stronger than those in the group given 0.3 mg/kg of prednisone , indicating a dose response . At 6 months , significant side effects occurred in the group treated with 0.75 mg/kg of prednisone , including weight gain , cushingoid appearance , and excessive hari growth . Only weight gain was observed in the group taking prednisone at a dose of 0.3 mg/kg . Importantly , no side effects were evident at 10 days or 1 month of treatment , despite improvement in muscle strength and function . We conclude that prednisone produces a rapid increase in muscle strength in patients with Duchenne dystrophy and that this improvement is maximal at a prednisone dosage of 0.75 mg/kg or less We previously reported the results of a r and omized , double-blind 6-month trial of prednisone therapy in which 102 boys aged 5 to 15 years with Duchenne muscular dystrophy received daily doses of 1.5 and 0.75 mg/kg per day and were compared with those receiving placebo . The strength and function in both prednisone-treated groups improved equally and were significantly better than in the placebo group . To compare alternate-day and daily dosing of prednisone with respect to benefits and adverse side effects , the placebo group was started on alternate-day prednisone therapy , and the treatment group regimens were changed to equivalent doses of alternate-day prednisone without breaking the double-blind nature . At the end of 6 months , the group that was changed from daily to alternate-day therapy had declined in strength back to levels observed 12 months previously , at the start of daily therapy . The group in which alternate-day therapy was started showed a significant improvement in strength at 3 months , similar in magnitude to the response of boys treated with daily therapy . However , their strength declined significantly in the subsequent 3 months compared with boys who received daily therapy . The frequency of side effects was not significantly different for alternate-day therapy compared with daily therapy . We conclude that alternate-day prednisone therapy effectively increases strength but does not sustain the improvement to the same extent as daily therapy or mitigate side effects
Conclusions Examining individual studies it appears that DFZ improves strength and functional outcomes compared to placebo , but it remains unclear if it has a benefit over prednisone on similar outcomes .
Two trials found that DFZ causes less weight gain than prednisone
Background To complete a systematic review and meta- analysis based on the clinical question : Is Deflazacort ( DFZ ) , a prednisolone derivative , an effective therapy for improving strength , with acceptable side effects , in children with Duchenne Dystrophy ( DD ) ?