Oxarol (maxacalcitol) / Roche, Maruho - LARVOL DELTA

Unlocking the therapeutic potential of the NFAT pathway in kidney diseases. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Ongoing studies indicate potential therapies, including anandamide, 11R-VIVIT and maxacalcitol to regulate NFAT levels in kidney disease. The present review discusses the role and regulation of NFAT in the pathogenesis of kidney diseases. This is focused on various preclinical studies that have shown NFAT downregulation as a potential therapeutic strategy against kidney disease setting the foundation for future clinical investigations."

Journal • Review • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • NFATC1

Marked hypercalcemia due to maxacalcitol ointment use in a patient with severe motor and intellectual disabilities. (PubMed, Pediatr Int) - No abstract available

Journal • Developmental Disorders • Endocrine Disorders • Mental Retardation • Metabolic Disorders

The Efficacy and Safety of Non-Biologic and Biologic Treatments in Palmoplantar Pustular Psoriasis and Palmoplantar Pustulosis: A Systematic Review and Network Meta-Analysis. (PubMed, Australas J Dermatol) - "Based on the P-scores from our NMA, guselkumab 100 mg was the most effective for PPPGA improvement, guselkumab 100 mg for PPPASI-75, oral cyclosporine 1 mg/kg/day for PPPASI-50, etretinate 1 mg/kg/day had the most adverse events, and secukinumab 300 mg was associated with the highest rate of serious adverse events. TRIAL REGISTRATION: PROSPERO registration number: CRD42023460842."

Journal • Retrospective data • Review • Dermatology • Immunology • Psoriasis • Pustular Psoriasis

Unusual Verrucous Skin Lesion in Diabetic Neuropathy Following Toe Amputation and Skin Grafting. (PubMed, Cureus) - "The lesion gradually resolved with the application of maxacalcitol ointment and the use of elastic stockings...Accurate differentiation between plantar warts and verrucous carcinomas is essential for appropriate management. Effective treatment and comprehensive patient education on foot care are crucial for improving outcomes and preventing further complications in patients with diabetes."

Journal • Dermatology • Diabetes • Diabetic Neuropathy • Human Papillomavirus Infection • Infectious Disease • Metabolic Disorders • Oncology • Pain • Squamous Cell Carcinoma • Type 2 Diabetes Mellitus

Vitamin D and HPV infection: clinical pearls (EADV-Sp 2024) - "Topical vitamin D derivatives, in the form of calcipotriene or maxacalcitol ointment or calcitriol solution, have been successful in treating warts, including anogenital lesions which are among the most difficult-to-treat warts Intralesional injection of vitamin D also had been especially beneficial in the regression warts... Immunotherapeutic interventions, including intralesional and topical vitamin D, has gained interests in the management of these lesion due to its simple application, good compliance, few side effects, high cure rates and low risk of recurrence."

Clinical • Dermatology • Human Papillomavirus Infection • Infectious Disease • IL2

Combined maxacalcitol/betamethasone butyrate propionate ointment has long-term sustained effects of inducing regulatory T cells and downregulating inflammatory response in imiquimod-induced psoriasiform dermatitis (AAD 2024) - "Th17-downregulation was observed until three weeks later in MCT/BBP-treated mice whereas it was not two weeks later in MCT-treated mice. MCT showed long-term effects of inducing Treg and IL-10 expression and MCT/BBP did of downregulating Th17-related cytokines in addition to it, which could contribute to long-term effects observed in the clinical practice."

Dermatitis • Dermatology • Immunology • Inflammation • Psoriasis • FOXP3 • IL10

The Vitamin D Receptor-BIM Axis Overcomes Cisplatin Resistance in Head and Neck Cancer. (PubMed, Cancers (Basel)) - "Similar results were obtained for the clinically used VitD analog Maxacalcitol. Collectively, by identifying, for the first time, the VDR/BIM axis, we here provide a molecular rationale for the reported anti-cancer activity of VitD/analogs in combination therapies. Our data also suggest its exploitation as a potential strategy to overcome cisplatin resistance in HNSCC and other malignancies by inducing additional pro-apoptotic pathways."

IO biomarker • Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BCL2 • BCL2L11 • CDH1 • VDR

Efficacy and Safety of Topical Treatments for Seborrheic Keratoses: A Systematic Review. (PubMed, J Dermatolog Treat) - "Topical treatments that yielded a good-to-excellent response include hydrogen peroxide, Maxacalcitol 25µg/g, BID Tazarotene 0.1% cream, 5% potassium dobesilate cream, 1% diclofenac sodium solution, urea-based solution, and 65% and 80% trichloroacetic acid. Topical hydrogen peroxide shows the greatest evidence for clinical clearance of seborrheic keratoses and may be a viable option for patients requesting non-invasive removal. No studies to our knowledge directly compare hydrogen peroxide to current first-line treatments.Meaning: There remains demand for topical treatments that reliably equate or exceed the efficacy of current first-line therapies."

Journal • Review • Oncology

Molecular docking study on vitamin D supplements to understand their interaction with VDR-RXRα heterodimer and VDRE of TAGAP gene. (PubMed, J Biomol Struct Dyn) - "In addition, the binding of the ligand-activated heterodimer complexes with VDREs of the TAGAP gene was also analyzed to comprehend the binding affinities of calcitriol and maxacalcitol to the gene. The current work utilizes in silico molecular docking and simulation analysis to understand the mechanism in each complex formation.Communicated by Ramaswamy H. Sarma."

Journal • Endocrine Disorders • Immunology • Inflammatory Arthritis • Metabolic Disorders • Rheumatoid Arthritis • Rheumatology

Daily dose of alfacalcidol at conversion from intravenous maxacalcitol in secondary hyperparathyroidism management. (PubMed, Ther Apher Dial) - No abstract available

Journal • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Orthopedics • Renal Disease • Secondary Hyperparathyroidism

Conversion from intravenous maxacalcitol to oral vitamin D in secondary hyperparathyroidism management. (PubMed, Clin Exp Nephrol) - No abstract available

Journal • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

Maxacalcitol Pharmacokinetic-Pharmacodynamic Modeling and Simulation for Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis. (PubMed, Drug Res (Stuttg)) - "On the basis of these population PK and PD analyses and the clinical study conducted in Japan, there is no clinically relevant difference between Taiwanese and Japanese in terms of serum Ca or PTH levels."

Clinical • Journal • PK/PD data • Endocrine Disorders • Renal Disease • Secondary Hyperparathyroidism

Bone responsiveness to parathyroid hormone is negatively associated with parathyroid hormone-lowering drug use in patients undergoing hemodialysis: a cross-sectional study. (PubMed, BMC Nephrol) - "Bone responsiveness to PTH is negatively correlated with the intravenous administration of a CaSR agonist and/or a VDRA in patients undergoing chronic HD."

Clinical • Journal • Observational data • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • TRAP

Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism: A Randomized Clinical Trial. (PubMed, Clin J Am Soc Nephrol) - "Etelcalcetide was more effective in increasing T value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs."

Clinical • Journal • Alzheimer's Disease • Chronic Kidney Disease • CNS Disorders • Dementia • Endocrine Disorders • Renal Disease • Secondary Hyperparathyroidism

A New Modified Experimental Meibomian Gland Injury Model: Partial Loss of Gland Due to Orifice Cauterization and the Alleviating Potential of 22-Oxacalcitriol. (PubMed, J Clin Med) - "The cornea and other ocular tissues were not affected by maxacalcitol ointment application during our two-month observation period. Altogether, this work indicates that maxacalcitol has therapeutic potential in the amelioration of initial injury of MG orifices caused by electrocautery."

Journal • Dermatology • Immunology • Inflammation • Psoriasis

Maxacalcitol (22-Oxacalcitriol (OCT)) Retards Progression of Left Ventricular Hypertrophy with Renal Dysfunction Through Inhibition of Calcineurin-NFAT Activity. (PubMed, Cardiovasc Drugs Ther) - "Our works indicated that OCT retards progression of LVH through calcineurin-NFAT pathway, which reveal a novel aspect of OCT in attenuating pathological LVH."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • Targeted Protein Degradation

Extragenital lichen sclerosus successfully treated by topical maxacalcitol/betamethasone butyrate propionate. (PubMed, Clin Exp Dermatol) - "Patients are usually asymptomatic or may present with slightly itchy, white papules with progressive development of parchment-like skin. Topical corticosteroids are recommended as first-line treatment; most patients are initially treated with potent topical corticosteroids."

Journal • Dermatology

Interventions for chronic palmoplantar pustulosis. (PubMed, Cochrane Database Syst Rev) - "Evidence is lacking for major chronic palmoplantar pustulosis treatments such as superpotent corticosteroids, phototherapy, acitretin, methotrexate, and ciclosporin. Risk of bias and imprecision limit our confidence. Maxacalcitol may be more effective than placebo in achieving clearance in the short term (low-quality evidence), and the risk of adverse effects is probably similar (moderate-quality evidence). Oral alitretinoin is probably no more effective than placebo in reducing severity, with a similar risk of adverse effects (moderate-quality evidence). Regarding biological treatments, we are uncertain of the effect of etanercept on clearance and the effect of ustekinumab on severity (low-quality evidence). Secukinumab and guselkumab are probably superior to placebo in reducing severity (moderate-quality evidence). Adverse events not requiring withdrawal were not reported for these treatments. Reporting of serious adverse effects was incomplete: compared to placebo,..."

Journal • Review • Dermatology • Dermatopathology • Immunology • Ocular Infections • Ocular Inflammation • Ophthalmology • Pruritus • Psoriasis

Early Response of the Parathyroid Gland to Withdrawal of a Calcimimetic Compound in Uremic Rats. (PubMed, Am J Physiol Renal Physiol) - "We examined the response of parathyroid glands to cinacalcet (Cina) withdrawal in uremic Sprague-Dawley rats fed a high-phosphate diet to develop secondary hyperparathyroidism and divided into groups treated with vehicle (UC), Cina, and Cina and maxacalcitol (Maxa), a vitamin D receptor activator (CiNa + Maxa). Continuous administration of cinacalcet may be necessary for better control of SHPT. Simultaneous use of a VDRA may be preferable in the timing of cinacalcet withdrawal."

Journal • Preclinical • Endocrine Disorders • Secondary Hyperparathyroidism

Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation. (PubMed, Int J Mol Sci) - "Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol) on AD-relevant mechanisms. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention."

Clinical • Journal • Alzheimer's Disease • Biosimilar • CNS Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor

A vitamin D analog inhibits Th2 cytokine- and TGFβ -induced periostin production in fibroblasts: a potential role for vitamin D in skin sclerosis. (PubMed) - "In vivo, OCT administration decreased the density of collagen bundles and POSTN expression in a BLM-induced scleroderma model. In addition to the previously reported immunosuppressive effect, the vitamin D analog OCT might be effective to treat scleroderma, in part through inhibition of Th2 cytokine- and TGFβ-induced POSTN expression."

Journal • Biosimilar • Fibrosis • Immunology • Inflammation • Systemic Sclerosis

Comparative pharmacokinetics of maxacalcitol in healthy Taiwanese and Japanese subjects. (PubMed, Heliyon) - "C of maxacalcitol was slightly lower (85%) in Taiwanese compared with that in Japanese and AUC of maxacalcitol in Taiwanese subjects was contrarily 15.0 (41.6%) higher than that in Japanese subjects, resulted in not much difference in pharmacokinetics of maxacalcitol between Taiwanese and Japanese. Moreover, maxacalcitol was well tolerated in both healthy Taiwanese and Japanese subjects."

Clinical • Journal • PK/PD data

"Fig. 2. Representative microphotographs of proliferating cell nuclear antigen staining in the normal control (NC; A), vehicle (UC; B), cinacalcet (Cina; C), and CINA and maxacalcitol (Maxa); D) group on day 0 (semiquantification of stain). ## p<0.01 vs. NC group; $$ p<0.01 vs. UC" (@DrDanMO)

PCNA

Repurposing the Psoriasis Drug Oxarol to an ointment adjuvant for the influenza vaccine. (PubMed, Int Immunol) - "Furthermore, cell type-specific Tslpr gene deletion or diphtheria toxin-mediated deletion of specific cell types, revealed that CD11c+ cells excluding Langerhans cells were responsible for the Oxarol-mediated GC reactions. These results indicate that active vitamin D3 is able to enhance the humoral response via Tslp induction in the skin and serves as a new vaccine adjuvant."

Clinical • Journal

Active vitamin D and vitamin D analogs stimulate fibroblast growth factor 23 production in osteocyte-like cells via the vitamin D receptor. (PubMed, J Pharm Biomed Anal) - "Therefore, the induction of FGF23 in osteocytes by vitamin D may be primarily mediated via VDR. The potential of 25(OH)vitamin D, paricalcitol, and maxacalcitol to induce FGF23 production was almost the same as that of 1α,25-dihydroxyvitamin D. However, falecalcitriol and eldecalcitol demonstrated a reduced potential to induce FGF23 compared with 1α,25-dihydroxyvitamin D. Our results demonstrate that FGF23 induction is different among the analogs of 1α,25-dihydroxyvitamin D. Therefore, an appropriate vitamin D analog should be chosen for each patient with mineral and bone disorder, considering its effect on FGF23 production."

Journal • FGF23