search text   Advanced Search

This Article Full Text Full Text (PDF) P3Rs: Submit a response Alert me when this article is cited Alert me when P3Rs are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wahn, U. Articles by de Prost, Y. Search for Related Content PubMed PubMed Citation Articles by Wahn, U. Articles by de Prost, Y.

Efficacy and Safety of Pimecrolimus Cream in the Long-Term Management of Atopic Dermatitis in Children

Ulrich Wahn, MD^*, Jan D. Bos, MD, Mark Goodfield, MD, Ruggero Caputo, MD^||, Kim Papp, MD, PhD^¶, Ahmed Manjra, MD^#, Attila Dobozy, MD^**, Carle Paul, MD, Stephen Molloy, PhD, Thomas Hultsch, MD, Michael Graeber, MD, Robert Cherill, MSc, Yves de Prost, MD^|||| for the Flare Reduction in Eczema with Elidel (Children) Multicenter Investigator Study Group

^* Department of Pediatric Pneumology and Immunology, Charité, Humboldt University, Berlin, Germany
Academic Medical Center, Amsterdam, Netherlands
Department of Dermatology, Leeds, UK
^|| I.R.C.C.S. Ospedale Maggiore, University of Milan, Italy
^¶ Probity Medical Research, Waterloo, Canada
^# 216 Hiway Medical Centre, Cape Town, South Africa
^** Szent-Györgyi Albert Orvostudományi Egyetem, Szeged, Hungary
Novartis Pharma AG, Basel, Switzerland
Novartis Pharmaceuticals Inc, New Jersey
^|||| Groupe Hospitalier Necker Enfants Malades, Paris, France

Objective. 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.

Methods. 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.

Results. 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.

Efficacy. 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).

Safety. 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.

Conclusions. 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.

Key Words: atopic dermatitis • SDZ ASM 981 • pimecrolimus • long-term management • antiinflammatory • flares • Eczema Area and Severity Index • Investigators’ Global Assessment • Elidel • randomized controlled study

Abbreviations: AD, atopic dermatitis • IGA, Investigators’ • Global Assessment • EASI, Eczema Area and Severity Index

This article has been cited by other articles:

				A. B. Fleischer Jr Diagnosis and Management of Common Dermatoses in Children: Atopic, Seborrheic, and Contact Dermatitis Clinical Pediatrics, May 1, 2008; 47(4): 332 - 346. [Abstract] [PDF]

				J. Faught, C. Bierl, B. Barton, and A. Kemp Stress in mothers of young children with eczema Arch. Dis. Child., August 1, 2007; 92(8): 683 - 686. [Abstract] [Full Text] [PDF]

				B. Cohen Review of Pimecrolimus Cream 1% in Children for the Treatment of Mild to Moderate Atopic Dermatitis Clinical Pediatrics, January 1, 2007; 46(1): 7 - 15. [PDF]

				S. M. Langan, K. S. Thomas, and H. C. Williams What is meant by a "flare" in atopic dermatitis?: a systematic review and proposal. Arch Dermatol, September 1, 2006; 142(9): 1190 - 1196. [Abstract] [Full Text] [PDF]

				M. Bigby Tacrolimus and pimecrolimus for atopic dermatitis: where do they fit in? Arch Dermatol, September 1, 2006; 142(9): 1203 - 1205. [Full Text] [PDF]

				H. C. Williams Atopic Dermatitis N. Engl. J. Med., June 2, 2005; 352(22): 2314 - 2324. [Full Text] [PDF]

				D. M Ashcroft, P. Dimmock, R. Garside, K. Stein, and H. C Williams Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials BMJ, March 5, 2005; 330(7490): 516. [Abstract] [Full Text] [PDF]

				Topical Calcineurin Inhibitors (TCIs) Journal Watch Dermatology, April 28, 2004; 2004(428): 7 - 7. [Full Text]

				Topical Calcineurin Inhibitors (TCIs) Journal Watch Pediatrics and Adolescent Medicine, April 12, 2004; 2004(412): 4 - 4. [Full Text]

				R. P. McLeod Lumps, Bumps, and Things That Go Itch in Your Office! The Journal of School Nursing, February 1, 2004; 20(1): 57 - 59. [PDF]

				B R Allen, M Lakhanpaul, A Morris, S Lateo, T Davies, G Scott, M Cardno, M-E Ebelin, P Burtin, and T J Stephenson Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients Arch. Dis. Child., November 1, 2003; 88(11): 969 - 973. [Abstract] [Full Text] [PDF]

				L. F. Eichenfield, A. W. Lucky, M. Boguniewicz, R. G. B. Langley, R. Cherill, and K. Marshall 1% Pimecrolimus Cream for Atopic Dermatitis Arch Dermatol, October 1, 2003; 139(10): 1369 - 1370. [Full Text] [PDF]

				{blacktriangledown}Pimecrolimus cream for atopic dermatitis DTB, May 1, 2003; 41(5): 33 - 36. [Abstract] [Full Text] [PDF]

				New Nonsteroidal Treatment for Atopic Dermatitis Journal Watch (General), July 23, 2002; 2002(723): 4 - 4. [Full Text]

	Home | My Pediatrics | Journal Information | Current Issue | Past Issues | Subscriptions & Services | Contact Us Click here for faster international access © 2002 American Academy of Pediatrics. All rights reserved.