Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid anti-inflammatory drug. A double-blind, randomized controlled trial of clobetasol versus pimecrolimus in patients with vulvar lichen sclerosus. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: results from 3 randomized, comparative studies. Pimecrolimus cream in the long-term management of atopic dermatitis in adults: a six-month study. Long-term safety and tolerability of pimecrolimus cream 1% and topical corticosteroids in adults with moderate to severe atopic dermatitis. 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study. Safety and efficacy of early intervention with pimecrolimus cream 1% combined with corticosteroids for major flares in infants and children with atopic dermatitis. A randomized study of the safety, absorption and efficacy of pimecrolimus cream 1% applied twice or four times daily in patients with atopic dermatitis.
Pimecrolimus cream 1% (Elidel, SDZ ASM 981), a nonsteroid selective inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). In this study we compared early intervention with pimecrolimus cream with treatment with a vehicle control.
                The purpose of this investigation was to assess whether early treatment in infants of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.
                In this 1-year, double-blind controlled study, 251 infants aged 3 to 23 months with AD were randomized 4:1 to a pimecrolimus-based regimen (n = 204) or a conventional treatment regimen (n = 47). Both groups used emollients for dry skin. Early AD signs and symptoms were treated either with pimecrolimus cream to prevent flares or, in the control group, with vehicle. Vehicle was used to maintain blinding conditions. In the event of flares, moderately potent corticosteroid was permitted in both groups. The primary efficacy end point was the incidence of flares at 6 months.
                Pimecrolimus significantly reduced the incidence of flares compared with control treatment (P <.001), with 67.6% versus 30.4% of patients completing 6 months with no flare and 56.9% versus 28.3% completing 12 months with no flare. Overall corticosteroid use was substantially lower in the pimecrolimus group: 63.7% versus 34.8% of patients did not use corticosteroids at all during the study. Pimecrolimus was also more effective than control treatment in the long-term control of pruritus and the signs of AD. There were no clinically significant differences in incidence of adverse events between the 2 treatment groups.
                Treatment with pimecrolimus of early signs and symptoms significantly modified the disease course in infants by reducing the incidence of flares and improving overall control of AD. Pimecrolimus was safe and well tolerated. Lichen sclerosus (LS) is a lymphocyte-mediated chronic cutaneous disorder with a predilection for the vulva. The current gold standard treatment is topical ultrapotent corticosteroids such as clobetasol.
                We sought to compare the safety and efficacy of clobetasol and pimecrolimus in the treatment of vulvar LS.
                This double-blind, randomized trial enrolled 38 women with biopsy-proven vulvar LS. This study consisted of a 2-week screening period and a 12-week treatment period. The primary efficacy variable was the change in inflammation, as determined by a dermatopathologist, on the biopsy specimens obtained at screening and at the week 12 visit. Secondary efficacy variables included the change from baseline in pruritus and burning/pain as assessed by patients using a visual analog scale and a clinical evaluation by the investigator.
                Clobetasol was found to be superior in improving inflammation when compared with pimecrolimus (P = .015). Both groups showed improvement in pruritus and burning/pain but this difference was not statistically significant (P = .32 and .93, respectively). Both clobetasol and pimecrolimus were found to be effective in decreasing both the total score on the Investigator Global Assessment (P = .001) and all 3 subscales. Serum levels of pimecrolimus and clobetasol did not approach levels of concern during the study period. No adverse events were reported.
                This study was limited by the relatively short study duration.
                Both clobetasol and pimecrolimus appear efficacious and well tolerated for the treatment of vulvar LS; however, clobetasol is more effective than pimecrolimus and should remain first-line therapy for LS.
                Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved. Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.
                Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion.
                BASELINE CHARACTERISTICS OF THE PATIENTS: The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline. PATIENT FOLLOW-UP AND EXPOSURE TO STUDY MEDICATION: The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously.
                Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had "severe" or "very severe" disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect. Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively).
                There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%--pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough. Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%--pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment. Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%--pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group. Laboratory values and vital signs showed no significant between-group differences. There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months.
                Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroids. To compare the efficacy and safety of tacrolimus ointment and pimecrolimus cream in adult and pediatric patients with mild to very severe atopic dermatitis (AD).
                One thousand and sixty-five patients were randomized to treatment in 3 multicenter, randomized, investigator-blinded, 6-week studies.
                Based on the Eczema Area Severity Index (EASI), tacrolimus ointment was more effective than pimecrolimus cream at the end of the study in adults (54.1% vs. 34.9%, respectively; P < .0001), in children with moderate/severe disease (67.2% vs. 56.4%, respectively; P = .04), in the combined analysis (52.8% vs. 39.1%, respectively; P < .0001), and at week 1 in children with mild disease (39.2% vs. 31.2%, respectively; P = .04). Tacrolimus was also more effective than pimecrolimus based on the Investigator Global AD Assessment (IGADA), improvement in percentage of total body surface area affected, and improvement in itch scores (P < or = .05), with a faster onset of action. There was no significant difference in the incidence of adverse events (AEs), including application site reactions in the 2 studies involving 650 children. Adults treated with tacrolimus experienced a greater number of local application site reactions on day 1; both groups reported a similar incidence of application site reactions thereafter. More pimecrolimus-treated patients than tacrolimus-treated patients withdrew from the studies because of a lack of efficacy (P < or = .03) or adverse events (P = .002; pediatric mild).
                Tacrolimus ointment is more effective and has a faster onset of action than pimecrolimus cream in adults and children with AD; their safety profiles are similar. Pimecrolimus cream (Elidel, SDZ ASM 981), a non-steroid inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms reduces the need for topical corticosteroids.
                To investigate the efficacy and safety of pimecrolimus cream 1% in the long-term management of adult AD.
                192 adults with moderate to severe AD were randomised (1:1) for twice daily (b.i.d.) treatment of early signs or symptoms of AD with either pimecrolimus cream 1% or vehicle cream (control group) to prevent progression to flares. Treatment was given as needed for 24 weeks. In the event of flares, a moderately potent corticosteroid (prednicarbate 0.25% cream) was permitted as rescue medication in both groups. The percentage of days on which a topical corticosteroid was used to treat disease flares was the main outcome measure.
                Corticosteroid medication was used on 14.2% (95% confidence interval, CI: 8.3-21.1) of the days of the 24-week treatment period in the pimecrolimus group and on 37.2% (95% CI: 30.4-44.0) of the days in the control group (p < 0.001). In total, 44.8% (43/96) of patients in the pimecrolimus group did not experience a flare compared with 18.8% (18/96) of patients in the control group. The median time to first flare was 144 days in the pimecrolimus group and 26 days in the control group (p < 0.001). Pimecrolimus treatment was also associated with improvement in signs and symptoms of AD, pruritus, patients' self-assessment and quality of life.
                Pimecrolimus cream 1% b.i.d. is an effective, well-tolerated, long-term treatment for AD in adults, substantially reducing the number of flares compared to a conventional therapy and consequently reducing or eliminating the need for corticosteroid treatment.
                Copyright 2002 S. Karger AG, Basel This randomized, double-blind, multi-centre study compared the long-term safety and tolerability of pimecrolimus cream 1% and topical corticosteroids (TCS) in 658 adults with moderate-severe atopic dermatitis (AD).
                Patients applied either pimecrolimus or TCS (i.e. 0.1% triamcinolone acetonide cream and/or 1% hydrocortisone acetate cream) twice daily to all affected areas until complete clearance or for up to 1 year. The study was approved by the institutional review board or ethics committee at each centre.
                A majority of patients treated with either pimecrolimus or TCS used the drug on a continuous basis over 1 year. In patients who had >30% of the body surface involved by AD, the incidence rate of all skin infections was significantly lower in the pimecrolimus group than in the TCS group (95% CI of the treatment difference: -25.3% to -3.4%). The most frequent application site reaction was burning (25.9% of patients on pimecrolimus and 10.9% on TCS), which was transient and mild-moderate in most cases. Three TCS-treated patients reported skin striae. There were no treatment-related serious or clinically significant systemic adverse events. Efficacy was better in patients on continuous TCS therapy, although patients completing the study were similarly well-controlled in both groups. About 42% of the pimecrolimus-treated patients were maintained for 1 year without TCS.
                Pimecrolimus demonstrated a favourable safety profile when used to treat adult patients with moderate-severe AD for up to 1 year. A significant proportion of patients could be maintained without TCS for a year. During the last decades, management of intertriginous psoriasis (IP) has been unsatisfactory because of the adverse effects associated with long-term corticosteroid application and the lack of alternatives. Recently, both pimecrolimus and tacrolimus have been investigated for this indication and shown to be safe and effective. So far, to our knowledge, a comparison of one of these drugs with standard regimens for IP has not been performed.
                A single-center, 4-week, double-blind, randomized, vehicle-controlled comparison study to assess the safety and efficacy of 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone valerate in the treatment of IP.
                Dermatologic hospital at Ruhr University of Bochum.
                Eighty adults with IP.
                Treatment of IP with 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone, or the vehicle once daily for 28 days.
                Mean reduction of the Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of treatment was considered the primary outcome measure, which was analyzed on an intention-to-treat basis. The secondary outcome was a visual analog scale score for itching.
                After 4 weeks of treatment, the 3 active compounds and the vehicle resulted in a significant decrease in mean M-PASI score (86.4% for 0.1% betamethasone, 62.4% for 0.005% calcipotriol, 39.7% for 1% pimecrolimus, and 21.1% for vehicle). The 0.1% betamethasone was significantly more effective than 1% pimecrolimus during the study period (P<.05). No significant difference was found between 0.005% calcipotriol and 0.1% betamethasone and between 0.005% calcipotriol and 1% pimecrolimus. The visual analog scale score for pruritus decreased by 78% for 0.1% betamethasone, 57% for 0.005% calcipotriol, 35% for 1% pimecrolimus, and 43% for the vehicle, again demonstrating a clear advantage for the corticosteroid (P<.05).
                The 1% pimecrolimus was shown to be less potent than 0.1% betamethasone in the treatment of IP. Considering the adverse-effect profile of long-term application of corticosteroids, occasional or intermittent rescue therapy with short-term topical corticosteroids and maintenance with a less potent agent, such as 1% pimecrolimus or 0.005% calcipotriol, might be appropriate for patients with IP in general practice. To assess early intervention with pimecrolimus combined with corticosteroid (CS) for major flares in patients with severe atopic dermatitis (AD).
                In this 6-month, double-blind, multicenter, randomized, vehicle-controlled, parallel-group in 35 US centers, 275 children aged 3 months to 11 years with mild to severe AD applied the study medication twice daily at first signs/symptoms of AD. For major flares not controlled with study medication, a mid-potency CS cream replaced the evening study drug for up to 3 weeks. The percentage of subjects with no major flares was the main outcome measure.
                Pimecrolimus reduced the major flare incidence and prolonged flare-free intervals. Significantly more pimecrolimus subjects (52%) had no major flares compared with vehicle subjects (34%; p = 0.007). Pimecrolimus significantly delayed the first flare (median, 53 days vs 13 days; p<0.001), and increased the time between flares (median, 31 days vs 15 days). Additionally, there was earlier pruritus improvement (median, day 3 vs day 6; p = 0.034) in the pimecrolimus group, as well as a reduced need for CS by 37% (p = 0.020) [corrected] Adverse events (AEs) incidence and type were comparable between groups. Combination therapy with pimecrolimus used at half the recommended dose did not shorten the mean flare duration or alter the AE profile.
                Early treatment of signs/symptoms of AD with pimecrolimus cream 1% provided an effective steroid-sparing option that reduced the incidence of major flares. Pimecrolimus cream 1% (Elidel), a non-steroid inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis, without corticosteroid-related side effects such as skin atrophy. It is indicated for twice-daily application. More frequent applications might be expected either to enhance efficacy or increase toxicity. This study compared the safety, efficacy and systemic absorption of pimecrolimus administered twice daily (recommended dose) and four times daily early in the treatment of patients with moderate to severe atopic dermatitis.
                Adolescent and adult patients with moderate to severe atopic dermatitis were randomly assigned to a twice daily (BID) treatment group (n = 24) or a four times daily (QID) group (n = 25). During days 1-7, patients in the QID group applied pimecrolimus four times daily, and patients in the BID group applied pimecrolimus twice daily plus vehicle equivalent twice daily. During days 8-21, all patients were required to use pimecrolimus twice daily and had the option to use up to two further daily treatments (pimecrolimus in the QID group and vehicle equivalent in the BID group). Blood sampling occurred 2, 4, and 6 hours after the first morning application on days 1 and 5 and then prior to the first morning application on days 8 and 15, and any time on day 22.
                Only 3 (12%) QID patients and 4 (17%) BID patients reported adverse events (primarily mild, transient application-site burning) with no significant difference between treatment groups in the frequency, type, or severity of adverse events. The median daily number of applications in the QID group during days 8-21 when two additional doses were optional remained at four. Pimecrolimus blood levels from a subgroup of 22 patients showed no difference in systemic exposure between the two dosing regimens. All but three (one in the QID group, two in the BID group) patients had blood levels below the limit of quantification; the highest single blood level of pimecrolimus measured in any patient was 1.37 ng/ml (QID group). Both the QID and BID regimens improved the signs and symptoms of atopic dermatitis similarly as measured by improvements in pruritus severity score, Investigator's Global Assessment, Eczema Area and Severity Index, percentage of body surface area affected, and patient's self-assessment of disease control.
                The data suggest that increasing pimecrolimus application from twice daily to four times daily to treat moderate to severe atopic dermatitis for up to 3 weeks does not alter the safety profile nor does it increase the efficacy of treatment. Systemic absorption of pimecrolimus applied BID and QID is minimal and is not different between dosing regimens. Patients and physicians familiar with the potential hazards of overuse of topical corticosteroids should be reassured that if pimecrolimus is applied at twice the recommended BID dose for short periods of time, there is no effect on safety, tolerability, or systemic absorption.
Topical pimecrolimus is less effective than moderate and potent corticosteroids and 0.1% tacrolimus. The therapeutic role of topical pimecrolimus is uncertain due to the absence of key comparisons with mild corticosteroids.