The OPTIMA Study

Messa, Piergiorgio; Macário, Fernando; Yaqoob, Magdi; Bouman, Koen; Braun, J.; Albertini, Beat von; Brink, Hans; Maduell, Francisco; Graf, Helmut; Frazão, João; Bos, Willem Jan W.; Torregrosa, Vicente; Saha, Heikki; Reichel, Helmut; Wilkie, Martin; Zani, Valter J.; Molemans, Bart; Carter, Dave; Locatelli, Francesco

doi:10.2215/cjn.03591006

Cited by 208 publications

(195 citation statements)

References 32 publications

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“…Consistent with previous findings, treatment with cinacalcet was associated with increased use of Ca-containing binders, possibly as a response to reductions in serum Ca, whereas participants on vitamin D analogs were more likely to use non-Ca-containing binders (36). However, it is unlikely that the observed differences in binder use would have affected our study results.…”

Section: Discussionsupporting

confidence: 90%

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism

Sprague

Wetmore

Gurevich³

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Cinacalcet and vitamin D are often combined to treat secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects on fibroblast growth factor-23 (FGF-23) concentrations in patients on hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during treatment of SHPT are evaluated.Design, setting, participants, & measurements A multicenter, randomized, open-label study to compare the efficacy of cinacalcet versus traditional vitamin D therapy for management of secondary hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a prospective, phase 4, multicenter, randomized, open-label study conducted globally. Participants (n=312) were randomized 1:1 to cinacalcet (n=155) or vitamin D analog (n=157) for 52 weeks. Levels of FGF-23 were measured at baseline and weeks 20 and 52. The absolute and percentage changes from baseline in plasma FGF-23, parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and calcium-phosphorus product (Ca3P) were assessed. Correlations and logistic regression were used to explore relationships between changes in FGF-23 and changes in PTH, Ca, P, and Ca3P from baseline to week 52 by treatment arm.Results Median (quartiles 1, 3) decrease in FGF-23 concentrations was observed in the cinacalcet arm (240%; 263%, 16%) compared with median increase in the vitamin D analog arm (47%; 0%, 132%) at week 52 (P,0.001). Changes in FGF-23 in both arms were unrelated to changes in PTH (cinacalcet: r=0.17, P=0.11; vitamin D analog: r=20.04, P=0.70). Changes in FGF-23 in the vitamin D analog but not the cinacalcet arm were correlated with changes in Ca (cinacalcet: r=0.11, P=0.30; vitamin D analog: r=0.32, P,0.01) and P (cinacalcet: r=0.19, P=0.07; vitamin D analog: r=0.49, P,0.001). Changes in FGF-23 were correlated with changes in Ca3P in both arms (cinacalcet: r=0.26, P=0.01; vitamin D analog: r=0.57, P,0.001). Independent of treatment arm, participants with reductions in P or Ca3P were significantly more likely to show reductions in FGF-23.Conclusions During treatment of SHPT, cinacalcet use was associated with a decrease in FGF-23 concentrations, whereas vitamin D analogs were associated with an increase. The divergent effects of these treatments on FGF-23 seem to be independent of modification of PTH. It is possible that effects of cinacalcet and vitamin D analogs on FGF-23 may be mediated indirectly by other effects on bone and mineral metabolism.

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Section: Discussionsupporting

confidence: 90%

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism

Sprague

Wetmore

Gurevich³

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…Several studies have reported the effect of cinacalcet on decreasing iPTH levels (1,4,5), with associations between cinacalcet administration and decreased iPTH levels in this study found to be consistent with those in randomized control studies (4,5) and a previous observational study (1). However, little is known about the effect of concomitant therapy with cinacalcet and VDRA (15), particularly with regard to the effect of VDRA dosage change in concomitant therapy.…”

Section: Discussionsupporting

confidence: 85%

Prescription Patterns and Mineral Metabolism Abnormalities in the Cinacalcet Era

Fukagawa

Fukuma

Ônishi³

et al. 2012

Clinical Journal of the American Society of Nephrology

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Summary Background and objectives Prescription patterns for hemodialysis patients with secondary hyperparathyroidism have varied widely since market introduction of cinacalcet. This study examined associations between prescription patterns and subsequent laboratory values. Design, setting, participants, & measurements Using a Mineral and Bone Disorder Outcomes Study for Japanese CKD Stage 5D Patients subcohort, 1716 prevalent hemodialysis patients (4048 sets for repeated measures between January 2008 and July 2009) with an intact parathyroid hormone (iPTH) level >180 pg/ml who used intravenous vitamin D receptor activator (VDRA) without cinacalcet were selected. Prescription patterns were defined based on cinacalcet administration (starting or not) and VDRA dosage change (decreased [<−25%], stable [−25% to 25%], or increased [>25%]). Proportion differences (PDs) were determined for decreasing iPTH levels by at least one category (<180, 180–299, 300–499, and ≥500 pg/ml) and for achieving target phosphorus (3.5–6.0 mg/dl) and calcium (8.4–10.0 mg/dl) levels, adjusting for potential confounders. Results The starting cinacalcet and increased VDRA patterns were associated with decreasing iPTH levels (PD, 0.25 and 0.13; 95% confidence intervals [95% CIs], 0.19–0.31 and 0.09–0.17, respectively); combination use had an additive association (PD, 0.34; 95% CI, 0.20–0.42). The starting cinacalcet and decreased VDRA combination was associated with simultaneously achieving target phosphorus (PD, 0.12; 95% CI: 0.04–0.20) and calcium (PD, 0.09; 95% CI, 0.01–0.17) levels. Conclusions Certain combinations of cinacalcet and VDRA were associated with decreasing iPTH and achieving targets for phosphorus and calcium. Combinations may prove advantageous versus VDRA alone in managing secondary hyperparathyroidism.

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“…The K/DOQI treatment goals were achieved in a higher proportion of dialysis patients with elevated serum PTH and Ca ϫ P levels in one such study (88). The superiority of the combination of standard therapy with cinalcalcet was also demonstrated in the OPTIMA trial, in which dialysis patrients with poorly controlled hyperparathyroidism were randomly allocated to receive either conventional care or a cinacalcet-based regimen (89). Again, a higher proportion of patients receiving cinacalcet in addition to conventional therapy versus conventional care alone achieved the targets for serum PTH, calcium, and phosphorus.…”

Section: Case In Favor Of Combination Of Vitamin D and Cinacalcetmentioning

confidence: 96%

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

Drüeke¹,

Ritz²

2009

Clinical Journal of the American Society of Nephrology

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The discovery of the calcium-sensing receptor (CaR) 15 yr ago was rapidly followed by the development of drugs modulating its activity, the so-called calcimimetics (increasing the CaR signal) and calcilytics (decreasing the CaR signal). The indication for calcimimetics is treatment of primary and secondary hyperparathyroidism, whereas calcilytics have potential for treatment of osteoporosis. A large number of clinical studies has shown that cinacalcet, the only presently available calcimimetic, effectively reduces serum parathyroid hormone in dialysis patients with secondary hyperparathyroidism. In contrast to the effect of active vitamin D derivatives, it simultaneously decreases serum calcium and phosphorus. Experimental studies showed a concomitant decrease in parathyroid hyperplasia. In the treatment of secondary hyperparathyroidism of dialysis patients, important questions remain unresolved, for example, whether there are reasons to prefer calcimimetics to active vitamin D derivatives and whether combined administration offers advantages compared with calcimimetics or active vitamin D given in isolation. For lowering parathyroid hormone, available evidence from recent studies suggests that combination therapy should be preferred to single drug treatment because of less side-effects and greater efficacy in controlling parathyroid overfunction. Future randomized controlled trial must answer whether calcimimetics impact on cardiovascular events or survival and whether in this respect there are differences between vitamin D sterols and calcimimetics.

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The OPTIMA Study

Cited by 208 publications

References 32 publications

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism

Prescription Patterns and Mineral Metabolism Abnormalities in the Cinacalcet Era

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

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