N Joshi, K Rajeshwari
Department of Pediatrics, Maulana Azad Medical College, New Delhi - 110 002, India
Department of Pediatrics, Maulana Azad Medical College, New Delhi - 110 002
Conventional oral steroids like prednisolone have various adverse effects both during short-term and long-term use. Hence a search for an alternative oral steroid with fewer side-effects is underway throughout the world. Deflazacort, an oxazoline derivative, is a step in this direction. The number of large randomized trials using deflazacort for steroid-responsive disorders in children is limited. Use of deflazacort has been explored largely in patients with Duchenne«SQ»s muscular dystrophy. Preliminary data suggest reduced osteoporosis, lesser growth retardation and weight gain with use of deflazacort, as compared to other steriods. In view of the limited data demonstrating superiority of deflazacort over the available oral steroids and its prohibitive cost, it is early to advocate widespread use of this drug in children.
|How to cite this article:|
Joshi N, Rajeshwari K. Deflazacort.J Postgrad Med 2009;55:296-300
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Joshi N, Rajeshwari K. Deflazacort. J Postgrad Med [serial online] 2009 [cited 2020 Apr 5 ];55:296-300
Available from: http://www.jpgmonline.com/text.asp?2009/55/4/296/58942
Corticosteroids are potent drugs with a wide application in various inflammatory and autoimmune disorders. While anti-inflammatory effects are inseparable from their metabolic effects, the goal of corticosteroid therapy is to obtain maximum clinical benefit with minimum adverse effects. Important adverse effects of long-term corticosteroid therapy include cushingoid appearance, osteoporosis, cataracts, psychosis, dyspepsia and immunosuppression leading to serious infections. Children are more vulnerable to their side-effects, particularly to effects on growth and adrenal suppression.
Deflazacort, an oxazoline derivative of prednisolone with anti- inflammatory and immunosuppressive activity, first became available in 1969. The severity of steroid-induced osteoporosis and growth retardation due to deflazacort is lesser than that associated with other steroids.  However, in 1998, the drug was withdrawn from the market as the Medicines Control Agency in the United Kingdom did not find it superior in terms of side-effects as compared to prednisolone. However, small patient numbers and open study designs make it difficult to interpret the clinical relevance.
Deflazacort is a synthetic glucocorticoid. Based on data obtained from various trials (including double-blind crossover studies, paired patient studies, and between-patient studies) involving 160 patients, the potency ratio of deflazacort vs. prednisolone was estimated to be 1.28.  It has been suggested that 6 mg of deflazacort has approximately the same anti-inflammatory potency as 5 mg prednisolone; although dosage ratios of 1:1.2 to 1:1.5 have also been reported across individual disease conditions such as rheumatoid arthritis,  asthma  and polymyalgia rheumatica  in adult patients.
Deflazacort is well absorbed after oral administration and converted to an active metabolite (D 21-OH) by plasma esterases. Peak plasma concentrations are achieved in 1.5-2 h and elimination plasma half life is 1.1-1.9 h. It is 40% protein-bound and is mainly (70%) excreted via the kidneys. Fecal excretion contributes to 30% of drug elimination. It has no affinity for transcortin (corticosteroid-binding-globulin).
Steroids supposedly enhance strength in patients of Duchenne's muscular dystrophy (DMD) by their effect on muscle proteolysis, myoblast proliferation, myogenic repair, inflammation and immunosuppression. Deflazacort, unlike prednisolone, demonstrated improved muscle repair and fiber growth in dystrophic mouse through an effect on promotion of myogenesis. 
Deflazacort has unanimously established its benefit in patients of DMD [Table 1]. ,,,,, Certain trials compared deflazacort to prednisolone to study its advantages [Table 2]. ,, It was seen that deflazacort preserved muscle strength and demonstrated a lesser increase in weight gain. ,,,,
These highlighted the advantage of deflazacort, since an increase in body weight could hamper motor performances, cause spinal deformity in wheelchair-bound patients and risk significant stress on muscle fibers threatening muscle necrosis. However, as studies with deflazacort involve small numbers and outcome measures are heterogeneous, a meta-analysis summarizing the trials of this drug would be useful. However, such an analysis has not yet been published.  Randomized controlled trials have shown that corticosteroids improve muscle function for variable periods of time in patients with DMD. However, those comparing the efficacy of deflazacort vis-à-vis prednisolone are scanty.
Penazola et al., noted that deflazacort administration is associated with milder side-effects as compared to prednisolone, when used for the management of first episode of nephrotic syndrome.  Lee et al., showed that deflazacort is equipotent to prednisolone in terms of efficacy in inducing remission.  Deflazacort, in equivalent doses, was noted to be superior to prednisolone in maintaining remission in patients with relapsing steroid-dependent nephrotic syndrome.  While deflazacort may serve as an alternative to prednisolone in nephrotic syndrome, more randomized controlled trials are required to clarify the matters further.
Juvenile idiopathic arthritis
Randomized double-blind trials in children  have demonstrated that deflazacort achieved disease control similar to prednisolone and a more pronounced and stable reduction in the number of circulating T lymphocytes and in CD4/CD8 ratio suggesting its advantage in immune-mediated diseases. More studies are awaited to clarify its role in treating such chronic inflammatory disorders.
In vitro, deflazacort was detected to be twice as potent as prednisolone in inhibiting eosinophil survival.  Recently, Gartner et al., suggested similar efficacy between the two drugs in improving pulmonary function and producing clinical improvement in acute moderate asthma in children.  Promotion of deflazacort in asthma depends further on larger randomized trials.
Children with renal transplant receiving prednisolone were switched to deflazacort in certain trials. These studies reported it to be well-tolerated with stable renal functions. ,, Rejection episodes in all these were comparable between the two drugs. Furthermore, pharmacokinetically, deflazacort dose adjustment for renal function is not necessary in children with chronic renal failure or after renal transplantation. 
Idiopathic thrombocytopenic purpura
Deflazacort appears as effective as prednisolone in its immunomodulating properties for the treatment of this hematological disorder in its acute  and chronic forms.  Unfortunately, limited heterogeneous studies preclude any meaningful inferences.
Drug-resistant epilepsy of childhood
In this solitary study, deflazacort proved to be as effective as hydrocortisone in the treatment of drug-resistant epilepsies with no reported adverse effects. 
Published data in children, evaluating deflazacort in other common disorders such as systemic lupus erythematosus (SLE), dermatomyositis, rheumatic carditis, acute lymphoblastic leukaemia, and lymphoma continues to be sparse.
Potential adverse effects with deflazacort therapy include candidiasis, cataract, dyspepsia, peptic ulcer, drug psychosis, impaired glucose tolerance, growth retardation, hirsutism, hypertension, hypokalaemia, muscle weakness, osteoporosis, pathological fracture, steroid facies, delayed wound healing. Of the limited studies in children, adverse effects commonly reported include cushingoid features, osteoporosis, weight gain, glucose intolerance and growth retardation.
Osteoporosis: Deflazacort proved to be less harmful to the cancellous bone than prednisolone in the only prospective, comparative, long-term histomorphometric study available to date. 
Research reveals that OPG (Osteoprotegerin) and RANKL (receptor activator of NF-KB ligand) are osteoblast-derived proteins, responsible for inhibition and stimulation of bone resorption respectively. Studies in adults have demonstrated a favorable ratio of serum RANKL: OPG, implying a potentially lesser bone loss with deflazacort. , The available but limited clinical trials in children suggest that deflazacort has some bone-sparing action as compared to prednisolone (when measured in terms of a lesser decline in the whole body mineral density). ,,,
Weight gain/obesity: Trials comparing deflazacort to prednisolone have suggested a lesser increase in weight not only in patients of Duchenne's muscular dystrophy ,,,, but also in those with nephrotic syndrome,  and Juvenile Rheumatoid Arthritis  and patients in the post-renal transplant state. ,
Growth retardation: Deflazacort therapy has been associated with a lesser decline in the growth velocity and an improved stature after one to two years. ,,
Cushingoid symptoms: Broyer et al.  and Ferraris et al.,  have demonstrated that the Cushingoid features were less with deflazacort as compared to prednisolone.
Glucose intolerance: Even as trials pursuing the metabolic effects of deflazacort vs. prednisolone in children are scanty, it appears to favour deflazacort by reporting favorable insulin: Glucose ratio. 
Adrenal suppression: Babadjanova observed that the equipotent dose for deflazacort vs. prednisolone (mg vs. mg) for cortisol suppression was 2.27.  Wajchenberg suggested that deflazacort's action in suppressing cortisol was confined to the pituitary while prednisolone was active on both, pituitary and adrenals.  Published clinical trials in children comparing the two are still awaited.
Pregnancy: Deflazacort crosses the placenta and doses equivalent to >40 mg prednisolone daily increase the risk of fetal and neonatal adrenal suppression. Deflazacort should be avoided during the second and third trimester.
Deflazacort withdrawal: Patients receiving more than 9 mg deflazacort/day for more than three weeks should refrain from abrupt withdrawal of the drug. Rapid reduction to physiological doses may be considered in illnesses unlikely to relapse on withdrawal of systemic steroids. However, once a daily dose equivalent to 9 mg deflazacort is reached, dose reduction should be slower to allow for the recovery of hypothalamic pituitary axis.
Deflazacort, a derivative of prednisolone appears promising. However, controlled clinical trials involving large number of children on deflazacort therapy for prolonged periods are still lacking. It is still early to advocate deflazacort for DMD as its superiority over the time-tested steroid, viz. prednisolone is still not established. In juvenile idiopathic arthritis, asthma and idiopathic thrombocytopenic purpura, it is perhaps as efficacious as prednisolone. In limited trials in children with nephrotic syndrome, it has been shown to be more efficacious than prednisolone in inducing remission and reducing relapse rates. Till date it appears to be more advantageous in children with chronic renal failure as dose adjustments are not needed. It may have a beneficial effect on bone mineral density, weight gain and growth velocity but warrants further evidence. From the available evidence, it is still premature to label deflazacort as superior to conventional steroids for various conditions both in terms of efficacy and safety profile.
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