Pimecrolimus Research Articles

Safety and efficacy of Pimecrolimus in atopic dermatitis among Chinese infants: a sub-group analysis of a five-year open-label study

IntroductionAtopic dermatitis (AD) exhibits difference in immune polarization between Caucasians and Asian races due to which an evaluation of the efficacy and safety of Pimecrolimus (PIM) in Asian population is called for. The current study addresses the need via a sub-group analysis of the PETITE study (NCT00120523) to evaluate the safety and efficacy of PIM in Chinese infants.Materials and methodsPatients with AD (≥3 months–<12 months of age) were randomized in a 1:1 ratio to either PIM 1% cream or topical corticosteroids (TCS). The primary endpoint was safety. The secondary endpoint was efficacy.Results120 patients were randomized to either PIM 1% or TCS (n = 61 for PIM, n = 59 for TCS). The most often reported adverse events were reported by similar proportions of patients treated with PIM or TCS. There was a progressive increase in overall IGA treatment success in infants treated with PIM (82.9%, p < .05, 95% CI: 70.4, 95.3) after 26 weeks which was comparable to the TCS group (88.5%, p < .05, 95% CI: 79.8, 97.1).ConclusionPIM showed an early and sustained efficacy in the Chinese sub-population with a substantial corticosteroid-sparing effect in patients with AD.

Influence of Molecular Structure and Physicochemical Properties of Immunosuppressive Drugs on Micelle Formulation Characteristics and Cutaneous Delivery.

The aim of this study was to investigate whether subtle differences in molecular properties affected polymeric micelle characteristics and their ability to deliver poorly water-soluble drugs into the skin. D-α-tocopherol-polyethylene glycol 1000 was used to prepare micelles containing ascomycin-derived immunosuppressants-sirolimus (SIR), pimecrolimus (PIM) and tacrolimus (TAC)-which have similar structures and physicochemical properties and have dermatological applications. Micelle formulations were prepared by thin-film hydration and extensively characterized. Cutaneous delivery and biodistribution were determined and compared. Sub-10 nm micelles were obtained for the three immunosuppressants with incorporation efficiencies >85%. However, differences were observed for drug loading, stability (at the highest concentration), and their in vitro release kinetics. These were attributed to differences in drug aqueous solubility and lipophilicity. Differences between the cutaneous biodistribution profiles and drug deposition in the different skin compartments pointed to the impact of differences in thermodynamic activity. Therefore, despite their structural similarities, SIR, TAC and PIM did not demonstrate the same behaviour either in the micelles or when applied to the skin. These outcomes indicate that polymeric micelles should be optimized even for closely related drug molecules and support the hypothesis that drugs are released from micelles prior to skin penetration.

Low-dose Pimecrolimus, an FDA-approved Calcineurin Inhibitor, Sensitizes Drug-resistant Cancer Cells via Strong P-gp Inhibition.

Co-treatment with calcineurin inhibitors, such as tacrolimus and cyclosporin A, can sensitize chemotherapy-resistant cancer cells with P-glycoprotein (P-gp)-over-expression. Pimecrolimus (PIME) is a clinically available calcineurin inhibitor with a structure similar to that of tacrolimus. Whether PIME can sensitize P-gp-over-expressing resistant cancer cells remains unclear. Cell viability assay, annexin V analyses, cellular morphology and density observation with a microscope, western-blotting, fluorescence-activated cell sorting (FACS), and analysis for P-gp inhibitory activity were performed to investigate the mechanism of action. PIME exhibited strong cytotoxicity to vincristine (VIC)-treated drug-resistant cell lines (KBV20C and MCF-7/ADR) over-expressing P-gp. Co-treatment with VIC and PIME increased apoptosis and down-regulated the ERK signaling pathway, resulting in G2 arrest. PIME could be co-administered with vinorelbine or eribulin to sensitize resistant KBV20C or MCF-7/ADR cancer cells. Moreover, PIME strongly inhibited the efflux of both rhodamine 123 and calcein-AM substrates through P-gp after 4 h of treatment, indicating that VIC+PIME sensitized cancer cells by inhibiting VIC efflux via direct PIME binding to P-gp. Low doses of PIME, tacrolimus, and cyclosporin A showed similar sensitizing efficiencies in resistant KBV20C cells. These drugs showed similar P-gp inhibitory activities using both rhodamine 123 and calcein-AM substrates, suggesting that calcineurin inhibitors generally have strong P-gp inhibitory activities that sensitize drug-resistant cancer cells with P-gp over-expression. PIME, currently used in clinics, can be repositioned for treating patients with P-gp-over-expressing resistant cancer (stem) cells.

A Double-Blind Randomized Controlled Trial Comparing the Efficacy of 0.0003% Calcitriol with 1% Pimecrolimus versus Placebo in the Management of Pityriasis Alba

A Double-Blind Randomized Controlled Trial Comparing the Efficacy of 0.0003% Calcitriol with 1% Pimecrolimus versus Placebo in the Management of Pityriasis Alba

Topical Calcineurin Inhibitors Aren't Associated with Excess Risk for Nonmelanoma Skin Cancers

Two calcineurin inhibitors are used topically to treat atopic dermatitis — tacrolimus (Protopic and generics) and pimecrolimus (Elidel and generics).

Autologous cultured melanocyte transplantation for the treatment of genital vitiligo

Objective To evaluate the efficacy of autologous cultured melanocyte transplantation in the treatment of genital vitiligo. Methods A retrospective analysis was carried out. From 2013 to 2016, 6 patients with genital vitiligo were enrolled from Department of Dermatology, Hangzhou Third People’s Hospital, who received the treatment with autologous cultured melanocyte transplantation. These patients aged 13-29 years, and the age of onset and disease duration ranged from 10 to 19 years and 2 to 10 years respectively. The area of white patches at the genital site ranged from 10 to 25 cm2. Before the transplantation, all the white patches of the 6 patients bad been stable for > 12 months. Two weeks after the treatment, pimecrolimus was applied to the wounds twice a day after crust shedding. When the patient achieved > 90% repigmentation of the white patches, pimecrolimus was applied once per three days for maintenance treatment. After the treatment, these patients were followed up for at least 24 months, and the longest follow-up period was 60 months. Results Obvious pigmentation was observed in all the 6 patients 2 months after the transplantation. Meanwhile, 3 patients achieved 80% repigmentation, 2 achieved 70% repigmentation, and 1 achieved 50% repigmentation. Six months after the treatment, 3 patients achieved 95% repigmentation, 2 achieved 80% repigmentation, and 1 still maintained 50% repigmentation. Twelve months after the treatment, 95% repigmentation was still maintained in the 3 patients, 90% repigmentation was achieved in 2 patients, and 1 patient maintained 50% repigmentation, and these outcomes lasted until the end of follow-up. During the follow-up, no adverse reactions were observed. Conclusion Autologous cultured melanocyte transplantation is effective for the treatment of stable genital vitiligo. Key words: Vitiligo; Cell transplantation; Transplantation, autologous; Melanocytes; Genitalia

Elucidating mechanistic insights into drug action for atopic dermatitis: a systems biology approach

BackgroundTopical Betamethasone (BM) and Pimecrolimus (PC) are widely used drugs in the treatment of atopic dermatitis (AD). Though the biomolecules and biological pathways affected by the drugs are known, the causal inter-relationships among these pathways in the context of skin is not available. We aim to derive this insight by using transcriptomic data of AD skin samples treated with BM and PC using systems biology approach.MethodsTranscriptomic datasets of 10 AD patients treated with Betamethasone and Pimecrolimus were obtained from GEO datasets. We used a novel computational platform, eSkIN (www.persistent.com/eskin), to perform pathway enrichment analysis for the given datasets. eSkIN consists of 35 skin specific pathways, thus allowing skin-centric analysis of transcriptomic data. Fisher’s exact test was used to compute the significance of the pathway enrichment. The enriched pathways were further analyzed to gain mechanistic insights into the action of these drugs.ResultsOur analysis highlighted the molecular details of the mechanism of action of the drugs and corroborated the known facts about these drugs i.e. BM is more effective in triggering anti-inflammatory response but also causes more adverse effect on skin barrier than PC. In particular, eSkIN helped enunciate the biological pathways activated by these drugs to trigger anti-inflammatory response and its effect on skin barrier. BM suppresses pathways like TNF and TLRs, thus inhibiting NF-κB while PC targets inflammatory genes like IL13 and IL6 via known calcineurin-NFAT pathway. Furthermore, we show that the reduced skin barrier function by BM is due to the suppression of activators like AP1 transcription factors, CEBPs.ConclusionWe thus demonstrate the detailed mechanistic insight into drug action of AD using a novel computational approach.

Safety and efficacy of pimecrolimus 1% cream for the treatment of atopic dermatitis in infants

Safety and efficacy of pimecrolimus 1% cream for the treatment of atopic dermatitis in infants

Topical Steroids vs. Pimecrolimus for Infants with Eczema

Pimecrolimus 1% cream, a topical calcineurin inhibitor approved for treatment of eczema in children aged ≥2 years, is often used when concerns arise

Comparison of topical application of tea polyphenol versus pimecrolimus versus tacrolimus for the treatment of monobenzone-induced vitiligo-like depigmentation in a mouse model

Objective To compare the therapeutic effect of topical application of tea polyphenol versus pimecrolimus versus tacrolimus for monobenzone-induced vitiligo-like depigmentation in mice. Methods Twenty-five 3-week-old female C57BL/6 mice were randomly and equally divided into 5 groups: negative control group, model group, tea polyphenol group, pimecrolimus group, tacrolimus group. Monobenzone 45% cream was applied to the back of mice in all the five groups except the negative control group once daily for 40 consecutive days to establish a model of vitiligo-like depigmentation. During the induction of depigmentation, the tea polyphenol group, pimecrolimus group and tacrolimus group were topically treated with tea polyphenol, pimecrolimus and tacrolimus respectively, and the model group remaining untreated. The depigmentation of hairs and skin was observed by naked eyes on a daily basis. Tissue specimens were obtained for histological examination from depigmented skin at non-application sites in mice after the end of the experiment. Hematoxylin-eosin staining was conducted to analyze lymphocytic infiltration, reflectance confocal microscopy to observe melanin and melanocytes in skin, and immunofluorescence assay to detect CD8+ T cell infiltration. Results Depigmentation occurred in both application sites and non-application sites of mice in the model group. Compared with the model group, the tacrolimus, pimecrolimus and tea polyphenol groups showed delayed depigmentation, reduced degree and area index of depigmentation, and attenuated lymphocytic infiltration and CD8+ T cell infiltration in depigmented maculae at application sites. In addition, the therapeutic effect of tacrolimus was stronger than that of pimecrolimus and tea polyphenol. Conclusion Tea polyphenol, pimecrolimus and tacrolimus are all effective for the treatment of vitiligo-like depigmentation in mice. Key words: Monobenzone; Tea polyphenol; Tacrolimus; Pimecrolimus; Vitiligo, animal model

The safety and feasibility analysis of viaminate capsule in the treatment of seborrheic dermatitis

Objective To investigate the safety and feasibility of viaminate capsule in the treatment of sebor-rheic dermatitis.Methods According to the digital table, 84 patients with seborrheic dermatitis were randomly divided into the observation group（n=42） and the control group（n=42）.The control group were treated with 1%pimecrolimus cream coated, 2 times/d.The observation group were treated with capsule viaminate, 50mg/times, 2 times/d,2 weeks for a course of treatment.The clinical efficacy of the two groups were observed.Results The ery thema,scaling,seborrhea,itching and other symptoms score and total score after treatment to 4 weeks,8 weeks of the two groups were compared（Erythema t=5.865,5.786;scaly t=6.112,5.886;seborrhea t=5.963,5.629;itching t=6.123,6.072.all P〈0.05）.The total effective rate of treatment 1 week,4 weeks,8 weeks of observation group were 57.14%,85.71%,95.24%.The control group were 42.86%,59.52%,80.95%,the difference was statistical-ly significant（χ2 =5.632,6.986,5.252,all P 〈0.05）.The patients relapse rate of the observation group was 2.38%,which was lower than 19.05%of the control group（χ2 =5.986,P〈0.05）,and the satisfaction rate of the observation group was 100.00%,which was higher than 76.19%of the control group（χ2 =6.123,P〈0.05）,but the adverse effects of the two groups had no statistically significant（χ2 =0.589,P〉0.05）.Conclusion Viaminate cap-sule can improve in a short period of time in patients with clinical symptoms of seborrheic dermatitis,the effect is sig-nificant,the recurrence rate is low,safe and effective. Key words: Dermatitis; Seborrheic Viaminate Capsules

Childhood Atopic Dermatitis Often Persists into Adulthood

Little has been reported about the natural history of atopic dermatitis (AD). When topical calcineurin inhibitors were approved for AD treatment, the FDA required manufacturers to conduct post-marketing safety studies. One such effort is the Pediatric Eczema Elective Registry (PEER), which enrolled patients aged 2 to 17 years with mild-to-moderate AD who had used pimecrolimus cream for >42 days in the prior 6 months; …

Effects of Pimecrolimus Compared with Triamcinolone Acetonide Cream on Skin Barrier Structure in Atopic Dermatitis: a Randomized, Double-blind, Right–Left Arm Trial

Patients with atopic dermatitis (AD) have an epidermal barrier dysfunction, which allows invasion of allergens to occur. Stratum corneum skin barrier is formed by corneocytes and extracellular lipids extruded from the epidermal lamellar bodies. In a controlled, randomized, double-blinded, right-left comparison study we investigated the effect of pimecrolimus (PIM) cream compared with triamcinolone acetonide cream (TA) on the skin barrier in 15 patients with symmetrical elbow lesions of AD. In punch biopsies, before and after treatment, skin lipid bilayer and lamellar body structure were examined by transmission electron microscopy (TEM). Partial Eczema Area and Severity Index (pEASi), stratum corneum hydration, and transepidermal water loss (TEWL) were monitored on days 1, 8 and 22. The pEASi was significantly more improved with TA compared with PIM, whereas stratum corneum hydration was slightly more improved after treatment with PIM. The TEM revealed a strong reduction in lamellar bodies in lesional skin of AD; only 32% of the lamellar bodies were normal. A significantly higher number of normal lamellar bodies was found after 3 weeks of treatment with PIM (58%; p < 0.005). An increase in lamellar bodies also occurred with TA treatment (46%; p < 0.05); however, significantly less than with PIM (p < 0.05). Clinical score and TEWL were more improved after treatment with TA, whereas the lamellar bodies were more normal after treatment with PIM.

The effect of pimecrolimus on expression of genes associated with skin barrier dysfunction in atopic dermatitis skin lesions

The mechanism of action of pimecrolimus (PIM) on atopic lesions is still under consideration. Thus far, we have evidence of its anti-inflammatory and immunomodulatory activity, and recent papers focus on its effect on epidermal barrier function. This study analysed changes in the expression of genes associated with skin barrier dysfunction in atopic dermatitis (AD) skin lesions after 2 weeks of exposure to PIM 1% cream. A real-time quantitative PCR analysis of selected epidermal differentiation complex genes and three alternative pathway keratins was performed in skin biopsies from 11 individuals with AD before and after PIM exposure. The real-time quantitative PCR analysis was compared to non-lesional skin in the same patients. Involucrin, a small proline-rich region (SPRR) 2C gene, and alternative pathway keratin 16 showed significant over-expression in lesional skin followed by significant decrease after PIM therapy. The SPRR1A gene, S100A9, and keratin 6A were also increased; however, the decrease after PIM treatment was not significant. The changes in S100 A2, A7 and A8 followed a similar course with borderline significance. SPRR4 had a significant decrease in expression in lesional versus non-lesional skin, which persisted after PIM treatment. No significant changes were detected in mRNA expression levels of filaggrin and loricrin. Our results suggest that PIM can be effective in restoring the epidermal barrier in patients with AD at least in part by its impact on expression of genes, which are important for the normal barrier function of skin.

Calcineurin inhibitors in the treatment of psoriasis

Calcineurin inhibitors can block calcineurin signaling pathway,thereby suppress T-cell activation.In the past,it was used as an immunosuppressant for immunoregulation after organ transplantation.Recent studies have found that they are also effective for the treatment of some inflammatory skin diseases such as psoriasis and atopic dermatitis.Their efficacy is close to that of corticosteroids but they do not induce skin atrophy.Tacrolimus ointment and pimecrolimus cream are expected to be an alternative to topical corticosteroids in the treatment of psoriasis.This review presents the clinical efficacy,mechanism of action and side effects of several calcineurin inhibitors in the treatment of psoriasis. Key words: Psoriasis; Calcineurin inhibitors; Therapy

Application of pimecrolimus in the treatment of allergic dermatoses such as dermatitis and eczema

As a new type of topical immunosuppressive agent,pimecrolimus is mainly used in the treatment of atopic dermatitis.Recently,the application range of pimecrolimus has been broadened and it has been widely used in many allergic dermatoses,such as atopic dermatitis,eczema,contact dermatitis,perioral dermatitis,et al.Several clinical studies have suggested that topical pimecrolimus twice daily has favorable effect with few side effects.Therefore,pimecrolimus may have a promising future in the treatment of allergic dermatoses such as dermatitis and eczema. Key words: Atopic dermatitis; Eczema; Pimecrolimus

Calcineurin inhibitors in the treatment of vitiligo

Vitiligo is an acquired hypopigmented disease characterized by the destruction of melanocytes.Many scholars consider that the pathogenesis of vitiligo is mainly associated with immune abnormalities.Topical calcineurin inhibitors have favorable efficacy in the treatment of vitiligo,and the efficacy is associated with the treatment regimen,course,application sites,duration and stage of vitiligo,etc.The combination with narrow-band ultraviolet B,308-nm excimer laser or other therapies may have synergistic effect on the efficiency of calcineurin inhibitors.Although calcineurin inhibitors are safe and effective in the treatment of vitiligo,further studies are needed to evaluate their long-term safety and stability. Key words: Vitiligo; Tacrolimus; Pimecrolimus; Therapy

Topical calcineurin inhibitors in the treatment of facial seborrheic dermatitis

Seborrheic dermatitis is a common inflammatory skin condition characterized by erythema,scaling and pruritus with a predilection for areas rich in sebaceous glands. It affects patients' quality of life to an extent. Since it is a chronic and recurrent disease, there is a strong need for safe alternatives for its longterm management. In the past, antifungals, topical corticosteroids and keratolytics were the mainstay of its therapy. Now topical calcineurin inhibitors provide a safe alternative treatment for it. It has been demonstrated that such calcineurin inhibitors as pimecrolimus and tacrolimus are effective and safe in the treatment of facialseborrheic dermatitis. Key words: Dermatitis,seborrheic; Tacrolimus; Pimecrolimus

Differential Effects of Corticosteroids and Pimecrolimus on the Developing Skin Immune System in Humans and Mice

Atopic dermatitis arises primarily in early infancy. In these patients, corticosteroids are used especially with great caution because of their side effects. Calcineurin inhibitors such as pimecrolimus (PIM) could be useful, but safety concerns have been raised in particular because of the lack of knowledge about their effects on the developing skin immune system. This study was designed to investigate the impact of PIM and corticosteroids on epidermal cells (EC) in infants and newborn mice. We found that the percentage of unfractionated viable infant ECs was significantly decreased in the presence of beta-methasone-17-valerate (BMV) but not PIM. Exposure of unfractionated infant ECs to BMV but not to PIM and vehicle control caused a significant inhibition of the upregulation of CD86 molecules on Langerhans cells (LC). The release of cytokines by LCs and ECs, cultured in the presence of BMV and PIM, was not significantly reduced compared with controls. Topical corticosteroid but not PIM application onto newborn mice induced apoptosis in some LC precursors. Our data suggest that similar to the situation in adult skin, corticosteroids may impair LC maturation as well as viability of ECs in infants, effects not seen with PIM.

Randomized Trial of Pimecrolimus Cream plus Colchicine Tablets versus Colchicine Tablets in the Treatment of Genital Ulcers in Behçet’s Disease

Background: Recurrent and painful genital ulcers are the hallmark of Behçet’s disease. Objective: To determine the efficacy of pimecrolimus (PIM) cream on the pain and healing time of genital ulcers. Methods: A total of 76 patients were randomized to either receive PIM cream plus colchicine (COL) tablets (1–2 g/day) or COL tablets (1–2 g/day) alone for 1 month. Clinical evaluations were performed in 68 patients at the baseline and on the 3rd, 7th, 10th, 14th and 28th days of treatment. Also, genital ulcer pain was evaluated using a verbal pain score at each visit. Safety was monitored through adverse event reporting and laboratory tests. Results: The mean healing time of genital ulcers was shorter in the PIM + COL group (4.2 ± 1.5 days) than the COL group (4.7 ± 1.8 days), without statistical significance (p = 0.399). Visual analog scale scores decreased in both groups significantly. Neither of the treatment modalities was found to be superior to the other; however, pain was relieved in 4.2 ± 0.5 days in PIM + COL group and in 5.5 ± 1.2 days in COL group in the intention to treat population (p = 0.023). Observed adverse events were transient. Conclusion: Compared to COL alone, COL + PIM cream shortens the pain duration without any significant effect on healing time.