|
|
| calcipotriol |
|
| CHEBI:50749 |
|
| A seco-cholestane that is 26,27-cyclo-9,10-secocholesta-5,7,10,22-tetraene carrying additional hydroxy substituents at positions 1, 3 and 24. It is used (as its hydrate) in combination with betamethasone dipropionate, a corticosteroid, for the topical treatment of plaque psoriasis in adult patients. |
|
This entity has been manually annotated by the ChEBI Team.
|
|
|
CHEBI:43947, CHEBI:31335
|
|
| ChemicalBook:CB2251448, eMolecules:30069809, ZINC000087515509 |
|
|
Molfile
XML
SDF
|
|
|
more structures >>
|
|
call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js Jmol JavaScript applet jmolApplet0_object__237403565981237__ initializing getValue debug = null getValue logLevel = null getValue allowjavascript = null AppletRegistry.checkIn(jmolApplet0_object__237403565981237__) call loadScript javascripts\jsmol\core\corestate.z.js viewerOptions: { "name":"jmolApplet0_object","applet":true,"documentBase":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50749","platform":"J.awtjs2d.Platform","fullName":"jmolApplet0_object__237403565981237__","display":"jmolApplet0_canvas2d","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol.MyStatusListener object]","codeBase":"https://www.ebi.ac.uk/chebi/javascripts/jsmol/","syncId":"237403565981237","bgcolor":"#000" } (C) 2012 Jmol Development Jmol Version: 13.2.7 $Date: 2013-10-01 11:35:15 -0500 (Tue, 01 Oct 2013) $ java.vendor: j2s java.version: 0.0 os.name: j2s Access: ALL memory: 0.0/0.0 processors available: 1 useCommandThread: false appletId:jmolApplet0_object (signed) starting HoverWatcher_1 getValue emulate = null defaults = "Jmol" getValue boxbgcolor = null getValue bgcolor = #000 backgroundColor = "#000" getValue ANIMFRAMECallback = null getValue APPLETREADYCallback = Jmol._readyCallback APPLETREADYCallback = "Jmol._readyCallback" getValue ATOMMOVEDCallback = null getValue CLICKCallback = null getValue ECHOCallback = null getValue ERRORCallback = null getValue EVALCallback = null getValue HOVERCallback = null getValue LOADSTRUCTCallback = null getValue MEASURECallback = null getValue MESSAGECallback = null getValue MINIMIZATIONCallback = null getValue PICKCallback = null getValue RESIZECallback = null getValue SCRIPTCallback = null getValue SYNCCallback = null getValue STRUCTUREMODIFIEDCallback = null getValue doTranslate = null language=en_US getValue popupMenu = null getValue script = null Jmol applet jmolApplet0_object__237403565981237__ ready call loadScript javascripts\jsmol\core\corescript.z.js call loadScript javascripts\jsmol\J\script\FileLoadThread.js starting QueueThread0_2 script 1 started starting HoverWatcher_3 starting HoverWatcher_4 The Resolver thinks Mol Marvin 09130719373D starting HoverWatcher_5 Time for openFile( Marvin 09130719373D 70 73 0 0 0 0 999 V2000 -5.4990 -3.8830 -1.0240 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6090 -0.0090 0.0290 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9610 -0.7800 1.0430 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.0370 -2.2680 0.6880 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2990 -2.5250 -0.6270 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8010 -2.2640 -0.4410 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6200 -0.8360 0.0350 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7010 -0.0180 -0.5170 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5560 1.3560 -0.0290 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5680 2.1250 -0.4860 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5990 3.6420 -0.3780 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4970 -0.3850 1.1360 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2980 4.1680 0.2250 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9360 3.5590 -0.4610 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 2.0620 -0.3090 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3460 1.5550 -1.1430 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1600 0.0390 -1.0530 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3730 -0.1310 -1.2490 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0190 1.2130 -0.8220 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6010 1.7150 1.1580 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0310 0.3350 2.1560 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0440 0.9800 0.2900 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1590 0.1090 -0.2290 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5210 -1.9170 -0.1810 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6170 2.3240 0.7440 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4810 -2.2520 0.9630 C 0 0 1 0 0 0 0 0 0 0 0 0 7.6870 -3.1340 0.6360 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8820 -1.6410 0.9100 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2290 -1.2220 -1.2090 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4060 -1.0460 0.3380 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5820 -0.4150 -0.8100 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1030 -2.8380 -0.5860 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8110 -1.3730 1.1780 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7540 0.4360 -1.0690 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5600 0.4880 1.1330 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1010 2.8170 -0.0990 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8110 2.9550 1.1200 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3470 2.1590 1.5360 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4920 1.6940 -1.6780 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5960 -0.3380 -2.2960 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7430 -0.9410 -0.6200 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7090 -0.4650 -1.8490 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4680 -0.3300 -0.0750 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2720 1.8930 -2.1770 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2510 1.7460 0.7000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0710 -0.3760 -1.3170 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6990 0.6540 2.9430 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9850 0.6010 2.1960 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4480 -0.6060 2.0030 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5370 0.9180 0.2940 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0810 -2.5620 0.5810 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5760 -2.8540 1.4830 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6900 -1.8600 -1.3970 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0230 -4.0030 -1.8580 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2830 -2.4030 -1.3900 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3980 -2.9520 0.3020 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7330 4.0700 -1.3720 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4340 3.9400 0.2560 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2670 5.2520 0.1140 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2730 3.9200 1.2860 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9340 3.8140 -1.5210 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8450 3.9350 0.0090 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3380 2.1690 1.4740 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5370 0.6330 1.2700 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4150 2.0970 1.7740 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0200 -2.3720 1.9430 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1210 -1.0010 0.0610 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3440 -1.3590 1.8560 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0210 -3.8340 1.4030 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7980 -3.4750 -0.3930 H 0 0 0 0 0 0 0 0 0 0 0 0 1 5 1 0 0 0 0 1 54 1 0 0 0 0 2 3 1 0 0 0 0 2 50 1 0 0 0 0 3 4 1 0 0 0 0 3 12 1 0 0 0 0 3 49 1 0 0 0 0 4 5 1 0 0 0 0 4 51 1 0 0 0 0 4 52 1 0 0 0 0 5 6 1 0 0 0 0 5 53 1 0 0 0 0 6 7 1 0 0 0 0 6 55 1 0 0 0 0 6 56 1 0 0 0 0 7 8 2 0 0 0 0 7 12 1 0 0 0 0 8 9 1 0 0 0 0 8 46 1 0 0 0 0 9 10 2 0 0 0 0 9 45 1 0 0 0 0 10 11 1 0 0 0 0 10 16 1 0 0 0 0 11 13 1 0 0 0 0 11 57 1 0 0 0 0 11 58 1 0 0 0 0 12 21 2 0 0 0 0 13 14 1 0 0 0 0 13 59 1 0 0 0 0 13 60 1 0 0 0 0 14 15 1 0 0 0 0 14 61 1 0 0 0 0 14 62 1 0 0 0 0 15 16 1 0 0 0 0 15 19 1 0 0 0 0 15 20 1 0 0 0 0 16 17 1 0 0 0 0 16 44 1 0 0 0 0 17 18 1 0 0 0 0 17 42 1 0 0 0 0 17 43 1 0 0 0 0 18 19 1 0 0 0 0 18 40 1 0 0 0 0 18 41 1 0 0 0 0 19 22 1 0 0 0 0 19 39 1 0 0 0 0 20 63 1 0 0 0 0 20 64 1 0 0 0 0 20 65 1 0 0 0 0 21 47 1 0 0 0 0 21 48 1 0 0 0 0 22 23 1 0 0 0 0 22 25 1 0 0 0 0 22 35 1 0 0 0 0 23 30 2 0 0 0 0 23 34 1 0 0 0 0 24 26 1 0 0 0 0 24 29 1 0 0 0 0 24 30 1 0 0 0 0 24 32 1 0 0 0 0 25 36 1 0 0 0 0 25 37 1 0 0 0 0 25 38 1 0 0 0 0 26 27 1 0 0 0 0 26 28 1 0 0 0 0 26 66 1 0 0 0 0 27 28 1 0 0 0 0 27 69 1 0 0 0 0 27 70 1 0 0 0 0 28 67 1 0 0 0 0 28 68 1 0 0 0 0 29 31 1 0 0 0 0 30 33 1 0 0 0 0 M END): 60 ms reading 70 atoms ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false 1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them. Default Van der Waals type for model set to Babel 70 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
|
InChI=1S/C27H40O3/c1- 17(6-13-25(29)20-8-9-20)23-11-12-24-19(5-4-14-27(23,24)3)7-10-21-15-22(28)16-26(30)18(21)2/h6-7,10,13,17,20,22-26,28-30H,2,4-5,8-9,11-12,14-16H2,1,3H3/b13-6+,19-7+,21-10-/t17-,22-,23-,24+,25-,26+,27-/m1/s1 |
| LWQQLNNNIPYSNX-UROSTWAQSA-N |
| [C@@H]1(C[C@@H](C/C(/C1=C)=C/C=C\2/[C@]3([C@](CCC2)([C@](CC3)([C@@H](/C=C/[C@@H](O)C4CC4)C)[H])C)[H])O)O |
|
|
drug allergen
Any drug which causes the onset of an allergic reaction.
|
|
|
drug allergen
Any drug which causes the onset of an allergic reaction.
antipsoriatic
A drug used to treat psoriasis.
|
|
View more via ChEBI Ontology
|
(1S,3R,5Z,7E,22E,24S)-26,27-cyclo-9,10-secocholesta-5,7,10,22-tetraene-1,3,24-triol
|
|
Calcipotriene
|
KEGG DRUG
|
|
Calcipotriol
|
KEGG DRUG
|
|
CALCIPOTRIOL
|
PDBeChem
|
|
MC 903
|
ChEBI
|
|
MC-903
|
ChEBI
|
|
MC903
|
ChEBI
|
|
Daivonex
|
ChemIDplus
|
|
Dovonex
|
DrugBank
|
|
112965-21-6
|
CAS Registry Number
|
KEGG DRUG
|
|
112965-21-6
|
CAS Registry Number
|
ChemIDplus
|
|
5309193
|
Reaxys Registry Number
|
Reaxys
|
Das K, Ranjan R, Kumar P, Chandra S (2024)
A Comparative Study of the Effectiveness and Safety of Topical Calcipotriol and Topical Methotrexate in Chronic Plaque Psoriasis.
Cureus 16, e59878 [PubMed:38854231]
[show Abstract]
Background Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Chronic plaque psoriasis, or psoriasis vulgaris, is the most common form of psoriasis. Present available preparations for mild to moderate chronic plaque psoriasis for topical use are local corticosteroids, coal tar, dithranol, tazarotene, calcipotriol, tapinarof, and calcineurin inhibitors. However, every preparation has its disadvantages. Calcipotriol, an active form of vitamin D, is available in topical form for dermatological use. Chronic plaque psoriasis is the chief medical use of calcipotriol for mild to moderate form. Methotrexate has dramatic results in psoriasis when used systemically. Now, topical formulation is being advocated in localized psoriasis, which is not associated with the side effects of the systemic form. Therefore, this study aimed to compare the effectiveness of topical calcipotriol and topical methotrexate on the basis of the psoriasis area severity index (PASI) in patients of chronic plaque psoriasis and compare their safety in terms of adverse effects. Methodology The total number of patients included in the study was 60. They were divided into two groups, with 30 patients each. One group was prescribed ointment calcipotriol 0.005% twice daily local application (Group C). The other group was prescribed methotrexate gel 1% twice daily local application (Group M). The patients were followed up on the fourth and eighth weeks, and at each time, thorough clinical examinations were conducted for all patients. The PASI score was calculated in each patient every time. Safety was assessed by biochemical parameters, and tolerability was assessed by the incidence of adverse effects. All the patients included in the study were investigated at baseline, fourth week, and eighth week. The data collected were transferred to a master chart and analyzed. Results For the patients in group C, the mean PASI score at 0 week was 5.93 ± 2.62, while at four weeks, the mean PASI score declined to 1.67 ± 1.13, and at eight weeks, the mean PASI score further declined to 0.67 ± 0.68. For the patients in group M, the mean PASI score at 0 week was 5.91 ± 2.22, while at four weeks, the mean PASI score declined to 1.91 ± 1.11, and at eight weeks, the mean PASI score further declined to 0.89 ± 0.72. Furthermore, there was no significant difference in the mean PASI score at various time points when compared between the two groups (p-value = 0.761, 0.296, 0.079, respectively). Thus, both drugs seem to be effective in treating mild- to moderate-grade chronic plaque psoriasis. Most of the patients in both groups showed marked clearance of the lesions. However, there were six patients in the calcipotriol group showing complete clearance of the lesions having mild-degree plaque psoriasis, as compared to three patients in the methotrexate group. In the present study, based on the comparison of safety and tolerability, four out of 30 patients (13.3%) in the calcipotriol group suffered skin irritation, whereas six out of 30 patients (20%) in the methotrexate group complained of a burning sensation. The adverse effects seen in the patients were transient and mild. Conclusion Topical calcipotriol and methotrexate were effective in reducing lesions in patients with chronic mild to moderate plaque psoriasis. Both drugs were well tolerated with mild and transient adverse effects and did not alter hematological and biochemical parameters. | Zheng M, Li H, Sun L, Cui S, Zhang W, Gao Y, Gao R (2024)
Calcipotriol abrogates TGF-β1/pSmad3-mediated collagen 1 synthesis in pancreatic stellate cells by downregulating RUNX1.
Toxicology and applied pharmacology 491, 117078 [PubMed:39214171]
[show Abstract]
RUNX1 with CBFβ functions as an activator or repressor of critical mediators regulating cellular function. The aims of this study were to clarify the role of RUNX1 on regulating TGF-β1-induced COL1 synthesis and the mechanism of calcipotriol (Cal) on antagonizing COL1 synthesis in PSCs. RT-qPCR and Western Blot for determining the mRNAs and proteins of RUNX1 and COL1A1/1A2 in rat PSC line (RP-2 cell). Luciferase activities driven by RUNX1 or COL1A1 or COL1A2 promoter, co-immunoprecipitation and immunoblotting for pSmad3/RUNX1 or CBFβ/RUNX1, and knockdown or upregulation of Smad3 and RUNX1 were used. RUNX1 production was regulated by TGF-β1/pSmad3 signaling pathway in RP-2 cells. RUNX1 formed a coactivator with CBFβ in TGF-β1-treated RP-2 cells to regulate the transcriptions of COL1A1/1A2 mRNAs under a fashion of pSmad3/RUNX1/CBFβ complex. However, Cal effectively abrogated the levels of COL1A1/1A2 transcripts in TGF-β1-treated RP-2 cells by downregulating RUNX1 production and hindering the formation of pSmad3/RUNX1/CBFβ complexes. This study suggests that RUNX1 may be a promising antifibrotic target for the treatment of chronic pancreatitis. | Azin M, Ngo KH, Hojanazarova J, Demehri S (2023)
Topical Calcipotriol Plus Imiquimod Immunotherapy for Nonkeratinocyte Skin Cancers.
JID innovations : skin science from molecules to population health 3, 100221 [PubMed:37731472]
[show Abstract]
Nonkeratinocyte cutaneous malignancies, including breast cancer cutaneous metastasis and melanoma in situ, are often poor surgical candidates. Imiquimod (IMQ), a toll-like receptor 7 agonist that activates innate immunity in the skin, is used to treat these cutaneous malignancies. However, IMQ's modest effect on the activation of adaptive immunity limits its efficacy as a monotherapy. In this study, we demonstrate that topical TSLP cytokine inducers-calcipotriol and retinoic acid-synergize with IMQ to activate CD4+ T-cell immunity against nonkeratinocyte cutaneous malignancies. Topical calcipotriol plus IMQ treatment reduced breast tumor growth compared with calcipotriol or IMQ alone (P < 0.0001). Calcipotriol plus IMQ-mediated tumor suppression was associated with significant infiltration of CD4+ effector T cells in the tumor microenvironment. Notably, topical calcipotriol plus IMQ immunotherapy enabled immune checkpoint blockade therapy to effectively control immunologically cold breast tumors, which was associated with induction of CD4+ T-cell immunity. Topical treatment with calcipotriol plus IMQ and retinoic acid plus IMQ also blocked subcutaneous melanoma growth. These findings highlight the synergistic effect of topical TSLP induction in combination with innate immune cell activation as an effective immunotherapy for malignancies affecting the skin. | Taraska V, Tuppal R, Olesen M, Bang Pedersen C, Papp K (2016)
A Novel Aerosol Foam Formulation of Calcipotriol and Betamethasone Has No Impact on HPA Axis and Calcium Homeostasis in Patients With Extensive Psoriasis Vulgaris.
Journal of cutaneous medicine and surgery 20, 44-51 [PubMed:26224733]
[show Abstract]
BackgroundFixed combination calcipotriol 50 µg/g (Cal; as hydrate) plus betamethasone 0.5 mg/g (as dipropionate; BD) has been formulated in an innovative aerosol foam.ObjectiveTo assess systemic safety of Cal/BD aerosol foam.MethodsIn a multicentre, single-arm, open-label, maximal-use systemic-exposure trial, adult patients with moderate to severe, extensive psoriasis (15%-30% of body surface area, including ≥30% of scalp) applied Cal/BD foam once daily. Endpoints were week 4 abnormal adrenocorticotropic hormone (ACTH) challenge test and change in albumin-corrected serum calcium, 24-hour urinary calcium excretion, and urinary calcium-creatinine ratio.Results35 patients reaching week 4 exhibited normal ACTH responses. At week 4, changes in calcium homeostasis were minor and not clinically relevant; no patients experienced elevations above normal. Disease severity generally improved, and 49% of patients achieved treatment success according to the Physician's Global Assessment of Disease Severity.ConclusionNo clinically relevant HPA axis or calcium homeostasis impact was observed with 4 weeks of once-daily Cal/BD foam in patients with extensive psoriasis vulgaris. | Zhao H, Li S, Luo F, Tan Q, Li H, Zhou W (2015)
Portulaca oleracea L. aids calcipotriol in reversing keratinocyte differentiation and skin barrier dysfunction in psoriasis through inhibition of the nuclear factor κB signaling pathway.
Experimental and therapeutic medicine 9, 303-310 [PubMed:25574190]
[show Abstract]
Psoriasis affects 2-4% of the population worldwide and its treatment is currently far from satisfactory. Calcipotriol and Portulaca oleracea have been reported to exhibit the capacity to inhibit inflammation in psoriatic patients and improve their clinical condition. However, the efficacy of a combination regimen of these two components remains unknown. The aim of the present study was to explore the therapeutic efficacy of P. oleracea extract combined with calcipotriol on plaque psoriasis and its potential mechanism. Eleven patients with plaque psoriasis were treated with humectant containing the active ingredients of P. oleracea extract, with or without 0.005% calcipotriol ointment in a right-left bilateral lesion self-control study. Differences were evaluated by investigation of the clinical efficacy, adverse effects, skin barrier function, histological structure, expression and proliferation of keratinocytes, differentiation markers (cytokeratin 10, filaggrin and loricrin), inflammatory factors [tumor necrosis factor (TNF)-α and interleukin (IL)-8], as well as the status of the nuclear factor κB (NF-κB) pathway. The combination of P. oleracea and calcipotriol was revealed to decrease adverse effects, reduce transepidermal water loss, potently reverse keratinocyte differentiation dysfunction, and inhibit the expression of TNF-α and IL-8 and the phosphorylation of the NF-κB inhibitor IκBα. This treatment is therefore anticipated to be suitable for use as a novel adjuvant therapy for psoriatic patients. | Keijsers RR, Joosten I, Hendriks AG, Koenen HJ, van Erp PE, van de Kerkhof PC (2015)
Balance of Treg versus T-effector cells during systemic treatment with adalimumab and topical treatment with calcipotriol-betamethasone dipropionate ointment.
Experimental dermatology 24, 65-67 [PubMed:25355140]
[show Abstract]
Diminished suppressive capacity of regulatory T cells (Treg) has been demonstrated in blood and in lesional skin of psoriatic patients. Treatment with anti-TNFα restored the number and function of circulating Treg in psoriasis. We aimed to study Treg in the skin of psoriatic patients undergoing topical treatment with calcipotriol-betamethasone dipropionate (CBD) ointment (n = 12) or systemic treatment with anti-TNFα agent adalimumab (n = 10). Skin biopsies were collected from patients with chronic plaque psoriasis who responded to the above-mentioned treatments with a SUM-score improvement of at least 50% (at the end of treatment). Biopsies were processed for immunohistochemistry. As Treg function is associated with a numerical balance between Treg and effector T cells, Foxp3/CD4 ratios were calculated. It appeared that both treatments cause a significant decrease in the presence of Foxp3+ cells. However, in patients that were treated with CBD ointment, we observed lower Foxp3/CD4 ratios after 8 weeks of treatment compared to baseline (t = 0: 0.41 ± 0.08; t = 8: 0.22 ± 0.04, P = 0.033), whereas in patients who were treated with adalimumab we observed an increase of the Foxp3/CD4 ratios after 1.5 and 16 weeks of treatment compared to baseline (t = 0: 0.25 ± 0.04; t = 1.5: 0.32 ± 0.06; t = 16: 0.49 ± 0.10, P = 0.15). Based on Foxp3/CD4 ratios, we can conclude that adalimumab treated skin differs from CBD treated skin with regard to the anti-inflammatory/inflammatory balance. We suggest that, in contrast to CBD ointment, adalimumab favours local Treg function in the skin. | Gong Q, Li X, Sun J, Ding G, Zhou M, Zhao W, Lu Y (2015)
The effects of calcipotriol on the dendritic morphology of human melanocytes under oxidative stress and a possible mechanism: is it a mitochondrial protector?
Journal of dermatological science 77, 117-124 [PubMed:25592908]
[show Abstract]
BackgroundVitiligo is an acquired pigmentary disorder of unknown etiology that is clinically characterized by the development of white macules in the skin related to the selective loss of melanocytes in those areas. Evidence shows that mitochondria might be a unifying target of reactive oxygen species (ROS) generation, cytokine production, catecholamine release and/or alteration of Ca(2+) metabolism that leads to melanocyte loss.ObjectiveTo assess the protective effect of calcipotriol on mitochondria of human melanocytes by investigating their dendritic morphology under oxidative stress.MethodsHuman melanocytes were treated with 0.05% H2O2 as well as various concentrations of calcipotriol, after which the retraction velocity of melanocyte dendrites was assessed. Detection of malondialdehyde (MDA) and superoxide dismutase (SOD) was performed as were the mitochondrial membrane potential (MMP) and intracellular calcium concentration ([Ca(2+)]i). Ultrastructural changes of mitochondria in melanocytes were observed by transmission electron microscopy. In addition, the expression of Beclin1, microtubule-associated protein 1 light chain 3 (LC3), dynamin related protein 1 (Drp1), mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2), which are related to autophagy and mitochondrial dynamics, were analyzed by Western blot.ResultsCalcipotriol reduced the retraction velocity of melanocyte dendrites. In addition, calcipotriol, from 20nM to 80nM, decreased the level of MDA, increased the activity of SOD, suppressed the reduction of MMP and recovered Ca(2+) homeostasis by reducing [Ca(2+)]i in a concentration-dependent manner. Observation by transmission electron microscopy suggested that calcipotriol might reduce the injury of mitochondria in melanocytes under oxidative stress. Furthermore, the expression of Beclin1, LC3-II/LC3-I, Mfn2 and Drp1 was higher in the calcipotriol-treated melanocytes than in the control or H2O2-treated melanocytes. The level of Mfn1 was almost unchanged, but was higher at a concentration of 80nM calcipotriol than in any other condition. The expression of Mfn2 and Drp1 decreased with increasing calcipotriol concentration.ConclusionOur study demonstrates the antioxidative effect of calcipotriol on melanocytes against oxidative damage. Moreover, calcipotriol could be a promising drug delivery strategy to protect melanocytes against oxidative damage in vitiligo through autophagy or mitophagy. | Dyring-Andersen B, Bonefeld CM, Bzorek M, Løvendorf MB, Lauritsen JP, Skov L, Geisler C (2015)
The Vitamin D Analogue Calcipotriol Reduces the Frequency of CD8+ IL-17+ T Cells in Psoriasis Lesions.
Scandinavian journal of immunology 82, 84-91 [PubMed:25904071]
[show Abstract]
The vitamin D analogue calcipotriol is an immunomodulatory drug widely used to treat psoriasis; however, how calcipotriol affects the immune cells in psoriasis lesions is not fully understood. The aim of this study was to investigate the effect of calcipotriol on the frequency of CD4(+) and CD8(+) T cells and innate lymphoid cells (ILC) and their production of IL-17A, IFN-γ and IL-22 in psoriasis lesions in patients with chronic plaque psoriasis. Eighteen patients with psoriasis were included, and two similar psoriasis lesions were chosen for each patient. One lesion was treated with calcipotriol (50 μg/g) and the other with vehicle twice a day for 14 days. The clinical effect was measured by degree of erythema, scaling and induration in each lesion (SUM score). Skin biopsies were collected for histological and immunohistochemical analyses. Skin-derived cells were isolated and analysed by flow cytometry. After 14 days of treatment with calcipotriol, a significant clinical and histological effect was seen; however, we found no differences in the frequency of CD4(+) and CD8(+) T cells or ILC between calcipotriol- and vehicle-treated skin. The main finding was a significant decrease in CD8(+) IL-17(+) T cells in skin-derived cells from calcipotriol-treated skin, which was further supported by the absence of CD8(+) IL-17(+) T cells in immunohistochemical staining of calcipotriol-treated skin. No changes in the frequency of IL-22(+) or IFN-γ(+) cells were observed. Our findings show that the vitamin D analogue calcipotriol reduces the frequency of CD8(+) IL-17(+) T cells in psoriasis lesions concomitant with clinical improvement. | Wu D, Wu C, Jin H (2015)
[Effects of calcipotriol on the expression of S100A8 in human keratinocytes].
Zhonghua yi xue za zhi 95, 1262-1264 [PubMed:26081515]
[show Abstract]
ObjectiveTo explore the effects of calcipotriol on the expression of S100A8 in human keratinocytes.MethodsCultured HaCaT cells were divided into 4 groups of blank without interventions, tumor necrosis factor-alpha (TNF-α) 24 h stimulation with 100 ng/ml TNF-α, calcipotriol 24 h stimulation with 10⁻⁵ -10⁻⁹ mol/L calcipotriol and calcipotriol+TNF-α 24 h stimulation. The relative expression of S100A8 mRNA was detected and calculated by real-time quantitative polymerase chain reaction (PCR).ResultsThe relative expression of S100A8 mRNA was up-regulated to (19.623 ± 3.486) folds (P < 0.01) under a 24 h stimulation of 100 ng/ml TNF-α versus blank. The expression of S100A8 was up-regulated to (5.029 ± 1.056) and (2.848 ± 0.612) folds (both P < 0.01) when cultured for 24 h with 10⁻⁷, 10⁻⁸ mol/L calcipotriol versus blank respectively. And the expression of S100A8 was down-regulated to (59.51 ± 3.31)% (P < 0.05) when cultured with 10⁻⁵ mol/L calcipotriol+TNF-α versus TNF-α-stimulated cells. The expression of S100A8 was up-regulated to (1.873 ± 0.153) folds (P < 0.01) when cultured with 10⁻⁷ mol/L calcipotriol+TNF-α versus TNF-α-stimulated cells.ConclusionsTNF-α induces a high expression of S100A8 in cultured human keratinocytes in vitro. Calcipotriol bi-directionally affects the expression of S100A8: A high concentration (10⁻⁵ mol/L) calcipotriol down-regulates while a low concentration (10⁻⁷ - 10⁻⁸ mol/L) calcipotriol up-regulates the expression of S100A8. | Sakabe J, Umayahara T, Hiroike M, Shimauchi T, Ito T, Tokura Y (2014)
Calcipotriol increases hCAP18 mRNA expression but inhibits extracellular LL37 peptide production in IL-17/IL-22-stimulated normal human epidermal keratinocytes.
Acta dermato-venereologica 94, 512-516 [PubMed:24419155]
[show Abstract]
Interleukins (IL)-17A and -22 are involved in the patho-genesis of psoriasis. Cathelicidin LL37 serves as not only antimicrobial peptide but also as autoinflammatory mediator. 1,25-Dihydroxyvitamin D3 analogues, such as calcipotriol, are used as topical treatment for psoriasis. However, the effect of calcipotriol on the mRNA expression/production of human cathelicidin antimicrobial protein (hCAP18) and LL37 peptide by IL-17A/IL-22-stimulated keratinocytes remains controversial. To evaluate the modulatory action of calcipotriol on the production of hCAP18 and LL37, we analysed hCAP18 mRNA expression and hCAP18/LL37 peptide production in IL-17A/IL-22-stimulated cultured human keratinocytes by real-time qPCR, ELISA, western blotting, and immunocytostaining. By western blotting, hCAP18 protein was detected in keratinocytes cultured for 72 h with IL-17/IL-22. Calcipotriol increased hCAP18 mRNA expression in IL-17/IL-22-stimulated keratinocytes. However, LL37 peptide in the culture supernatants was reduced by calcipotriol. Immunostaining revealed that the overproduced LL37 resides within the cells. LL37 promotes psoriasis via interaction with extracellular DNA, but may suppress psoriasis by interfering cytosolic DNA. | Iraji F, Tajmirriahi N, Siadat AH, Momeni I, Nilforoushzadeh MA (2014)
Efficacy of adding topical simvastatin to topical calcipotriol on improvement of cutaneous plaque psoriasis.
Advanced biomedical research 3, 11 [PubMed:24592364]
[show Abstract]
BackgroundPsoriasis is a common dermatologic disorder, with fluctuating response to treatment. Considering the proven immunomodulatory effects of oral simvastatin in psoriasis, this trial study was enrolled to determine whether the topical form has also antipsoriatic effects. Vitamin D analogs known to be effective and are considered the first line of therapy in mild to moderate cases. In this study, the efficacy of topical calcipotriol 0.005% ointment (as a standard method of treatment for psoriasis) versus combination of calcipotriol plus topical simvastatin is compared in the treatment of psoriasis.Materials and methodsA total of 80 subjects with symmetric psoriasis who had body surface involvement up to 20% were divided randomly into 2 groups. Group A were treated with calcipotriol 0.005% ointment twice daily and Group B with calcipotriol 0.005% ointment twice daily and simvastatin 3% ointment twice daily for 12 weeks. The results were evaluated by a Blind Dermatologist using psoriasis area severity index (PASI) score at baseline, 4(th), 8(th) and 12(th) week of treatment. In a similar way, a subjective assessment performed by patients based on photo-evaluation at the end of the study.ResultsDespite a continuous reduction in PASI score in both groups, according to both physician (P = 0.603) and patient (P = 0.243) assessment topical simvastatin was not statistically more effective than conventional treatment of psoriasis at the end of the study.ConclusionThis study indicates that topical simvastatin is not associated with significant impacts in the treatment of psoriasis as compared to oral form. This study indicates that psoriasis is a systemic disorder with variable skin manifestations. | Usategui A, Criado G, Del Rey MJ, Faré R, Pablos JL (2014)
Topical vitamin D analogue calcipotriol reduces skin fibrosis in experimental scleroderma.
Archives of dermatological research 306, 757-761 [PubMed:24788893]
[show Abstract]
Vitamin D analogues can reduce TGF-β pro-fibrotic signaling in dermal fibroblasts, but they may also induce a potentially pro-fibrotic thymic stromal lymphopoietin (TSLP)-dependent Th2 cytokine local response. We have analyzed the net effect of topical vitamin D analogue calcipotriol (CPT) on the cytokine profile and the development of fibrosis in experimental model of bleomycin-induced fibrosis. Mice were simultaneously treated with topical CPT or vehicle cream and skin fibrosis was measured by collagen deposition, Masson's trichrome staining and hydroxyproline content. Cytokine and TSLP gene expression was evaluated by quantitative RT-PCR. We showed that in bleomycin injected skin, CPT administration significantly enhanced TSLP and IL-13 gene expression, but did not modify the expression of other cytokines. Skin fibrosis and hydroxyproline content were significantly reduced in CPT compared to vehicle-treated mice. In normal skin, topical administration of CPT lacked a direct pro-fibrotic effect. Our results demonstrate that topical CPT superinduces the expression of the TSLP/IL-13 Th2 axis in fibrotic skin, but it has a net anti-fibrotic effect. These data support the therapeutic use of topical vitamin D analogues for skin fibrosis. | Norsgaard H, Kurdykowski S, Descargues P, Gonzalez T, Marstrand T, Dünstl G, Røpke M (2014)
Calcipotriol counteracts betamethasone-induced decrease in extracellular matrix components related to skin atrophy.
Archives of dermatological research 306, 719-729 [PubMed:25027750]
[show Abstract]
The calcipotriol/betamethasone dipropionate fixed-combination gel is widely used for topical treatment of psoriasis vulgaris. It has been hypothesized that calcipotriol counteracts glucocorticoid-induced skin atrophy which is associated with changes in the extracellular matrix (ECM). To elucidate the combined effects of calcipotriol and betamethasone on key ECM components, a comparative study to the respective mono-treatments was carried out. The effect on collagen I synthesis, matrix metalloproteinase (MMP) secretion, and hyaluronic acid (HA) production was investigated in primary human fibroblast and keratinocyte cultures as well as in a human skin explant model. We show that calcipotriol counteracts betamethasone-induced suppression of collagen I synthesis. Similarly, calcipotriol and betamethasone have opposing effects on MMP expression in both fibroblasts and keratinocytes. Moreover, calcipotriol is able to restore betamethasone-impaired HA synthesis in keratinocytes and prevent betamethasone-induced epidermal thinning in minipigs upon treatment with the calcipotriol/betamethasone gel. In summary, our results show for the first time in primary human skin cultures that calcipotriol reduces early signs of betamethasone-induced skin atrophy by modulation of key ECM components. These results indicate that the calcipotriol component of the fixed-combination gel counteracts the atrophogenic effects of betamethasone on the skin. | Sun J, Dou W, Zhao Y, Hu J (2014)
A comparison of the effects of topical treatment of calcipotriol, camptothecin, clobetasol and tazarotene on an imiquimod-induced psoriasis-like mouse model.
Immunopharmacology and immunotoxicology 36, 17-24 [PubMed:24286371]
[show Abstract]
The interleukin-23/interleukin 17A (IL-23/IL-17A) cytokine axis plays a critical role in the pathogenesis of psoriasis. In this study, we report the effects of topical calcipotriol, camptothecin, clobetasol and tazarotene on the treatment of imiquimod (IMQ)-induced psoriasis-like inflammation, the development of which is dependent on the IL-23/IL-17A axis. IMQ-induced epidermal hyperplasia and inflammation in the BALB/c mouse ear were significantly inhibited following clobetasol treatment but not calcipotriol, camptothecin or tazarotene treatments. Real-time polymerase chain reaction showed that the mRNA levels of IL-17A, IL-17F, IL-22, IL-1β, IL-6 and TNF-α in ear skin were significantly decreased by clobetasol. In addition, we observed that calcipotriol, camptothecin and tazarotene failed to show any inhibitory effects on the IL-23/IL-17A/IL-22 axis. We also found that clobetasol treatment inhibited the proliferation of γδ T cells and C-C chemokine receptor type 6 (CCR6) expression induced by IMQ. Calcipotriol, camptothecin and tazarotene not only failed to inhibit this proliferation but also enhanced retinoic acid-related orphan receptor γ (RORγ) expression in IMQ-induced psoriasis-like inflammation. In conclusion, we suggest that clobetasol induces the relief of IMQ-induced psoriasis-like inflammation in a mouse model but that calcipotriol, camptothecin and tazarotene cannot. Therefore, we suggest that more in-depth studies on pharmacological effects of tazarotene, camptothecin and calcipotriol should be carried out. | Khandpur S, Sahni K (2014)
An open label prospective randomized trial to compare the efficacy of coal tar-salicylic Acid ointment versus calcipotriol/betamethasone dipropionate ointment in the treatment of limited chronic plaque psoriasis.
Indian journal of dermatology 59, 579-583 [PubMed:25484388]
[show Abstract]
BackgroundChronic plaque psoriasis is a common papulosquamous skin disorder, for which a number of topical agents are being used including coal tar, topical steroids and more recently topical calcipotriol/betamethasone dipropionate. There is no study comparing purified coal tar preparation with calcipotriol/betamethasone dipropionate ointment in limited chronic plaque psoriasis.Aims and objectivesA prospective randomized open label controlled trial to compare the efficacy and safety of topical application of coal tar-salicylic acid ointment with calcipotriol/betamethasone dipropionate ointment applied once at night for 12 weeks for the treatment of limited chronic plaque psoriasis.Materials and methodsA total of 62 patients of limited chronic plaque psoriasis (body surface area <10%) were randomized into two treatment groups: Group A received topical application of 6% coal tar with 3% salicylic acid ointment and Group B received calcipotriol/betamethasone dipropionate, once at night for 12 weeks. Results were assessed based on psoriasis area severity index (PASI) scores and patient global assessment (PGA) at each visit.ResultsMean PASI was significantly lower at week 2 (P = 0.01) and week 4 follow-up (P = 0.05) and the mean reduction in PASI was significantly higher at week 2 (P = 0.02) with calcipotriol/betamethasone than coal tar-salicylic acid, but this difference was not sustained at subsequent follow-up visits. Similarly, PGA scores at weeks 2 and 4 were significantly lower with calcipotriol/betamethasone dipropionate ointment (P = 0.003 and P = 0.007 respectively). There was no significant difference in any parameter during subsequent follow-up visits or at the end of the treatment phase (12 weeks).ConclusionTopical nightly application of calcipotriol/betamethasone dipropionate ointment leads to an initial, more rapid reduction in disease severity, but the overall outcome parameters are comparable in the two treatment groups. | Pommergaard HC, Burcharth J, Rosenberg J, Raskov H (2014)
Topical combination of diclofenac, calcipotriol, and difluoromethylornithine has beneficial effects comparable to 5-fluorouracil for the treatment of non-melanoma skin cancer in mice.
Journal of chemotherapy (Florence, Italy) 26, 105-110 [PubMed:24090798]
[show Abstract]
Non-melanoma skin cancer (NMSC) is the most common form of skin cancer. Owing to the significant adverse effects of existing treatments, alternatives are needed. The aim of this study was to evaluate the use of topically administered combination therapy and 5-flurouracil (5-FU) for the treatment of UVB induced NMSC in a mouse model. Ninety-six SKH-1 mice were randomized to one placebo group and two treatment groups (diclofenac+calcitriol+difluoromethylornithine (DFMO) and 5-FU). After UVB radiation for 20 weeks, the mice with tumours were treated topically for the following 17 weeks. Both treatments significantly reduced the number of tumours, number of mice with tumours as well as tumour area size compared with placebo. As the clinical use of 5-FU may induce more adverse effects, a combination of diclofenac+calcitriol+DFMO could be a promising alternative. Human studies are warranted to determine the beneficial effects and possible adverse effects of this new treatment. | Lambert J, Hol CW, Vink J (2014)
Real-life effectiveness of once-daily calcipotriol and betamethasone dipropionate gel vs. ointment formulations in psoriasis vulgaris: 4- and 12-week interim results from the PRO-long study.
Journal of the European Academy of Dermatology and Venereology : JEADV 28, 1723-1731 [PubMed:24533503]
[show Abstract]
BackgroundPsoriasis is most often treated using topical therapies such as the once-daily fixed combination of calcipotriol and betamethasone dipropionate, which is available as a gel and an ointment. To date, there have been no direct comparisons of patient perspectives on the two formulations.ObjectiveTo describe and compare patients' perspectives on calcipotriol and betamethasone gel and ointment formulations, including real-life effectiveness, adherence behaviour, treatment satisfaction and health-related quality of life (QoL), during long-term psoriasis vulgaris management, according to interim findings from the PRO-long study.MethodsPRO-long is a multicentre, prospective, observational, 52-week cohort study in patients prescribed fixed-combination calcipotriol (50 μg/g) and betamethasone (0.5 mg/g; as dipropionate) gel or ointment for long-term psoriasis management. Difference in effectiveness at 4 and 12 weeks was assessed by comparing the proportion of patients with controlled (mild or very mild) disease, according to the Patient's Global Assessment. Additional patient questionnaires were used to assess adherence behaviour, treatment satisfaction (nine-item Treatment Satisfaction Questionnaire for Medication) and health-related QoL (Skindex-29).ResultsA total of 156 patients were included in the analysis. In single items of the adherence behaviour and treatment satisfaction questionnaires, patients preferred the gel over the ointment as convenient, easy to use and fast to apply. Post hoc analysis demonstrated significant differences between gel and ointment for convenience and application time. More patients had controlled disease at week 12 with gel (71.9%) vs. ointment (65.7%); however, the difference was not statistically significant (primary end point; P = 0.40).ConclusionThis interim analysis supports fixed-combination calcipotriol and betamethasone gel as more convenient, easier to use and faster to apply than the ointment formulation in real-life conditions according to patients with psoriasis vulgaris. Furthermore, a numerical difference in patient-reported real-life effectiveness was seen in favour of the gel, although this was not statistically significant. | Yang DF, Chen JH, Chiang CP, Huang Z, Lee JW, Liu CJ, Chang JL, Hsu YC (2014)
Improve efficacy of topical ALA-PDT by calcipotriol through up-regulation of coproporphyrinogen oxidase.
Photodiagnosis and photodynamic therapy 11, 331-341 [PubMed:24907534]
[show Abstract]
BackgroundTopical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) is effective for treating oral precancerous lesions. The aim of this in vivo and in vitro study was to examine whether the efficacy of topical ALA-PDT could be further improved by calcipotriol (CAL).MethodsPrecancerous lesions in the buccal pouch of hamsters were induced by dimethylbenz(a)anthracene (DMBA). Lesions were treated with multiple topical ALA-PDT with or without CAL pretreatment. ALA-induced protoporphyrine IX (PpIX) was monitored by in situ fluorescence measurement. The effect of CAL on heme-related enzymes (CPOX, PPOX, and FECH) were examined in an in vitro model using human squamous cell carcinoma (SCC) cells (SCC4, SAS) using Western blots.ResultsFluorescence spectroscopy revealed that PpIX reached its peak level in precancerous epithelial cells of buccal pouch at 2.5 or 3.5h without or with CAL pretreatment, respectively. Both treatment regimens showed similar response rates, but the complete response was achieved after 5 times of ALA-PDT and 3 times of CAL-ALA-PDT (p<0.001). Pretreatment of SCC cells with 10(-8) or 10(-7)M CAL could result in a significant cell death (p<0.05) and an elevation of CPOX protein level.ConclusionTopical CAL can improve the efficacy of ALA-PDT in treating precancerous lesions, likely through the increase in CPOX level and in PpIX production. | Naga Sravan Kumar Varma V, Maheshwari PV, Navya M, Reddy SC, Shivakumar HG, Gowda DV (2014)
Calcipotriol delivery into the skin as emulgel for effective permeation.
Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society 22, 591-599 [PubMed:25561873]
[show Abstract]
The objective of this work is to formulate and evaluate an emulgel containing calcipotriol for treatment of psoriasis. Emulgels have emerged as a promising drug delivery system for the delivery of hydrophobic drugs. Isopropyl alcohol and polyethylene glycol have been employed as permeation enhancers. Formulation chart is made with seven formulations, evaluated for physical parameters, drug content, viscosity, thixotropy, spreadability, extrudability, mucoadhesion, diffusion studies, skin irritation test along with short term stability studies. Carbopolis is reported to have a direct influence on appearance and viscosity of final formulation. The photomicroscopic evaluations showed the presence of spherical globules in size range of 10-15 μm. Rheograms revealed that all the formulations exhibited pseudoplastic flow. Optimized formulation (F6) had shown 86.42 ± 2.0% drug release at the end of 8 h study. The release rate through dialysis membrane and rat skin is higher when compared to commercial calcipotriol ointment. Hence it is concluded that calcipotriol can be delivered topically with enhanced penetration properties when formulated as emulgel. | van Geel MJ, Mul K, Oostveen AM, van de Kerkhof PC, de Jong EM, Seyger MM (2014)
Calcipotriol/betamethasone dipropionate ointment in mild-to-moderate paediatric psoriasis: long-term daily clinical practice data in a prospective cohort.
The British journal of dermatology 171, 363-369 [PubMed:24593129]
[show Abstract]
BackgroundPsoriasis in children has a significant negative impact on the quality of life (QoL) and effective treatment can improve this. The two-compound ointment calcipotriol 50 μg g(-1) and betamethasone dipropionate 0·5 mg g(-1) is an effective treatment option for moderate-to-severe psoriasis in adults.ObjectivesTo study prospectively the effectiveness and safety of calcipotriol/betamethasone dipropionate ointment in paediatric patients with mild-to-moderate plaque psoriasis in daily clinical practice and to investigate the influence on QoL.MethodsData were obtained from a prospective, longitudinal paediatric psoriasis registry, called Child-CAPTURE. Severity was assessed using the Psoriasis Area and Severity Index (PASI) and body surface area (BSA). The Children's Dermatology Life Quality Index (CDLQI) was used to assess QoL and visual analogue scores (VAS) for pain and itch were collected. For safety data the number of (serious) adverse events was recorded.ResultsSeventy-three patients (mean age 10·8 years, range 3-18) were treated for a median time of 35·0 weeks (range 1·0-176·0). At week 12, mean PASI decreased 15·4% (from 5·2 to 4·4), BSA barely changed, and median CDLQI decreased significantly from 5·5 to 4·0. VAS scores for pain and itch declined. At week 24, mean PASI decreased to 4·3 (17·3%). No related serious adverse events were observed.ConclusionsIn this daily clinical practice study in paediatric psoriasis, calcipotriol/betamethasone dipropionate ointment initially improved mild-to-moderate psoriasis and then maintained its effect. In addition, it improved QoL, with few adverse events. | Lala SG, Parbhoo KB, Verwey C, Khan R, Dangor Z, Moore D, Pettifor JM, Martinson NA (2014)
The effect of topical calcipotriol or zinc on tuberculin skin tests in hospitalised South African children.
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 18, 388-393 [PubMed:24670691]
[show Abstract]
BackgroundThe tuberculin skin test (TST) is used to help diagnose tuberculosis (TB) in acutely ill hospitalised children. OBJECTIVE To investigate the potential augmentative effect of topical calcipotriol (a vitamin D analogue) or zinc on TST induration.MethodsThree TSTs were performed among 64 hospitalised children; each site was covered with topical aqueous cream (control), calcipotriol or zinc and assessed 24 and 48 h later by investigators blinded to all topical applications.ResultsTSTs were reactive in 15 (23.4%) children, of whom 13 (20.3%) were TST-positive. Topical calcipotriol and zinc induced TST positivity in two children with reactive but negative control TSTs. These treatments, however, did not significantly increase TST positivity rates. In children with reactive TSTs, the median 48 h induration diameter was not significantly different between the control, calcipotriol- or zinc-treated groups, which were respectively 12.0 (25%-75% IQR 5.0 - 18.0), 14.0 (25%-75% IQR 10.0 - 15.0) and 12.0 (25%-75% IQR 8.0 - 15.0) mm. Topical treatments did not induce TST reactivity or TST positivity in children with culture-confirmed TB disease (n = 4), human immunodeficiency virus infection (n= 18) or kwashiorkor (n = 9).ConclusionsTopical calcipotriol or zinc does not induce TST reactivity or significantly increase TST positivity rates in acutely ill hospitalised children. However, further studies are required to assess the effects of topical treatments on TST positivity in severely malnourished children. | Akdeniz N, Yavuz IH, Gunes Bilgili S, Ozaydın Yavuz G, Calka O (2014)
Comparison of efficacy of narrow band UVB therapies with UVB alone, in combination with calcipotriol, and with betamethasone and calcipotriol in vitiligo.
The Journal of dermatological treatment 25, 196-199 [PubMed:23441902]
[show Abstract]
ObjectiveThe purpose of this study is to compare the efficacy of three therapies in the treatment of non-segmental vitiligo: a combination of topical calcipotriol, narrowband-ultraviolet B (NB-UVB), and betamethasone therapies; a combination of NB-UVB and topical calcipotriol; and NB-UVB alone.Material and methodsForty-five patients with non-segmental vitiligo presenting to our Dermatology clinic were recruited to participate in the study. Patients were randomly divided into three groups. For each patient the size of the depigmented areas was assessed according to the rule of nines. The first group was treated with a combination of topical calcipotriol, NB-UVB, and betamethasone therapies. The second group was treated with a combination of NB-UVB and topical calcipotriol and third group was treated with NB-UVB alone. Since the patients' vitiligo lesions had similar phototypes, all patients were started with 0.1 j/cm(2), regardless of their skin phototype. The dose of NB-UVB was increased 10% in each session and no further increment was done after reaching 2.5 j/cm(2). Treatment effectiveness was evaluated according to the percentage improvement in repigmentation. The quality of life of the patients was measured by the Dermatology Life Quality Index (DLQI).ResultsThe patients were aged from 13 to 55 years (mean: 25.29). The duration of disease ranged from 3 months to 20 years. Family history was positive for vitiligo in 10 patients (22.2%). The percentage of recovery after treatment was 63.33% ± 7.55 in group 1, 60.67% ± 5.75 in group 2, and 46.67% ± 7.98 in group 3. There was no statistically significant difference between groups 1 and 2, and groups 2 and 3, but there was a statistically significant difference between groups 1 and 3 (p = 0.0048).ConclusionsIn conclusion, NB-UVB-alone therapy and the combined therapies are effective treatment options in the treatment of vitiligo. Future studies with larger groups are warranted to confirm our results. | Saraceno R, Camplone G, D'Agostino M, De Simone C, Di Cesare A, Filosa G, Frascione P, Gabellini M, Lunghi F, Mazzotta A, Peris K, Scotto Di Luzio G, Calvieri S, Simonacci M, Chimenti S (2014)
Efficacy and maintenance strategies of two-compound formulation calcipotriol and betamethasone dipropionate gel (Xamiol® gel) in the treatment of scalp psoriasis: results from a study in 885 patients.
The Journal of dermatological treatment 25, 30-33 [PubMed:23621170]
[show Abstract]
BackgroundPrevious studies showed the efficacy of a formulation containing calcipotriol and betamethasone dipropionate for the treatment of psoriasis.ObjectiveTo investigate maintenance strategies of a formulation containing calcipotriol (50 µg/g) and betamethasone dipropionate (0.5 mg/g) for the treatment of scalp psoriasis.Materials and methodsNine-hundred and four patients were screened and randomised on a 1:1 basis in two groups: maintenance of two applications per week (group A) versus on-demand therapy (group B). Clinical evaluation was performed at weeks 0, 2, 4, 8 and 12.ResultsEight-hundred and eighty-five patients were randomised: 441 in group A and 444 in group B. From week 2, both groups showed a significant clinical improvement compared with baseline; at weeks 8 and 12, group A demonstrated a higher clinical response compared with group B (p < 0.05). This difference was statistically significant (OR 0.47, 95% CI 0.37, 0.60).ConclusionsThe maintenance of twice-weekly application versus on-demand treatment of calcipotriol/betamethasone dipropionate gel is more effective and is associated with a lower rate of relapse. | Bagot M, Grossman R, Pamphile R, Binderup L, Charue D, Revuz J, Dubertret L (1994)
Additive effects of calcipotriol and cyclosporine A: from in vitro experiments to in vivo applications in the treatment of severe psoriasis.
Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie 317, 282-286 [PubMed:7994616]
[show Abstract]
We report that calcipotriol (CPT) is a potent inhibitor of lymphocyte proliferation in mixed epidermal cell lymphocyte reactions. In this model, CPT and cyclosporine A (CsA) have synergistic effects. These results have led to a randomised double-blind therapeutic study protocol in patients with severe psoriasis. In these patients, topical CPT and sub-therapeutic doses of CsA (2mg/kg/d) induce disappearance of cutaneous lesions. This therapeutic association may minimize secondary side effects of both drugs. |
|
