Compared clinical efficacy and bone metabolic effects of low-dose deflazacort and methyl prednisolone in male inflammatory arthropathies: a 12-month open randomized pilot study

Saviola, Gianantonio; Abdi-Ali, Lul; Eddin, Samia Shams; Coppini, Alessandro; Cavalieri, F; Campostrini, Lorella; Sacco, Silvano; Bucci, Mariarosaria; Cirino, Giuseppe; Rossini, Maurizio

doi:10.1093/rheumatology/kem030

Cited by 24 publications

(11 citation statements)

References 42 publications

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“…30 Both deflazacort and prednisone significantly reduce serum osteocalcin levels. 31,32 In contrast, vamorolone increased osteocalcin levels, suggesting loss of deleterious bone effects (supplemental table 10 available from Dryad, doi.org/10.5061/dryad.1rd4hc7).…”

Section: Discussionmentioning

confidence: 99%

Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function

et al. 2019

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ObjectiveTo study vamorolone, a first-in-class steroidal anti-inflammatory drug, in Duchenne muscular dystrophy (DMD). MethodsAn open-label, multiple-ascending-dose study of vamorolone was conducted in 48 boys with DMD (age 4-<7 years, steroid-naive). Dose levels were 0.25, 0.75, 2.0, and 6.0 mg/kg/d in an oral suspension formulation (12 boys per dose level; one-third to 10 times the glucocorticoid dose in DMD). The primary goal was to define optimal doses of vamorolone. The primary outcome for clinical efficacy was time to stand from supine velocity. ResultsOral administration of vamorolone at all doses tested was safe and well tolerated over the 24-week treatment period. The 2.0-mg/kg/d dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks of vamorolone treatment vs natural history controls), without evidence of most adverse effects of glucocorticoids. A biomarker of bone formation, osteocalcin, increased in vamorolone-treated boys, suggesting possible loss of bone morbidities seen with glucocorticoids. Biomarker outcomes for adrenal suppression and insulin resistance were also lower in vamorolone-treated patients with DMD relative to published studies of glucocorticoid therapy. ConclusionsDaily vamorolone treatment suggested efficacy at doses of 2.0 and 6.0 mg/kg/d in an exploratory 24-week open-label study. Classification of evidenceThis study provides Class IV evidence that for boys with DMD, vamorolone demonstrated possible efficacy compared to a natural history cohort of glucocorticoid-naive patients and appeared to be tolerated.

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Section: Discussionmentioning

confidence: 99%

Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function

et al. 2019

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“…However, corticosteroids are well known to cause osteopenia after long-term use and this side effect can cause major problems in clinical practice118. Several factors that facilitate GIO development have already been decoded1920 but identification of still unknown regulators/inducers is presently on going with different transgenic and/or knockout mice.…”

Section: Discussionmentioning

confidence: 99%

Strain dependent differences in glucocorticoid-induced bone loss between C57BL/6J and CD-1 mice

Ersek

Santo

Vattakuzhi

et al. 2016

Sci Rep

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We have investigated the effect of long-term glucocorticoid (GC) administration on bone turnover in two frequently used mouse strains; C57BL/6J and CD1, in order to assess the influence of their genetic background on GC-induced osteoporosis (GIO). GIO was induced in 12 weeks old female C57BL/6J and CD1 mice by subcutaneous insertion of long-term release prednisolone or placebo pellets. Biomechanical properties as assessed by three point bent testing revealed that femoral elasticity and strength significantly decreased in CD1 mice receiving GC, whereas C57BL/6J mice showed no differences between placebo and prednisolone treatment. Bone turnover assessed by microcomputer tomography revealed that contrary to C57BL/6J mice, prednisolone treated CD1 mice developed osteoporosis. In vitro experiments have underlined that, at a cellular level, C57BL/6J mice osteoclasts and osteoblasts were less responsive to GC treatment and tolerated higher doses than CD1 cells. Whilst administration of long-term release prednisolone pellets provided a robust GIO animal model in 12 weeks old CD1 mice, age matched C57BL/6J mice were not susceptible to the bone changes associated with GIO. This study indicates that for the induction of experimental GIO, the mouse strain choice together with other factors such as age should be carefully evaluated.

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“…Deflazacort,9 an oxazoline derivative of prednisolone, was initially thought to be as effective as prednisone while inducing fewer AEs, but there was a problem with the real equivalence ratio compared with prednisone10 and this drug has not become a major breakthrough. Knowledge about the mechanisms of GCs leading to beneficial effects (predominantly by the genomic effects of transrepression) and to AEs (predominantly by the genomic effects of transactivation) led to the development of selective GC-receptor agonists (SEGRAs) or dissociating GCs 11.…”

Section: Developments To Improve the Therapeutic Ratio Of Gcsmentioning

confidence: 99%

Modified release prednisone in patients with rheumatoid arthritis

Jacobs

Bijlsma

2010

Annals of the Rheumatic Diseases

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Compared clinical efficacy and bone metabolic effects of low-dose deflazacort and methyl prednisolone in male inflammatory arthropathies: a 12-month open randomized pilot study

Abstract: The correct equivalence ratio of DFZ to MP is 1.875:1, and of DFZ to prednisolone 1.5:1. We found a relative prevalence of bone resorption compared to bone formation in the first 6 months of treatment. The trend of OPG requires further investigation.

Cited by 24 publications

References 42 publications

Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function

Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function

Strain dependent differences in glucocorticoid-induced bone loss between C57BL/6J and CD-1 mice

Modified release prednisone in patients with rheumatoid arthritis

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