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ORIGINAL ARTICLE
Year : 2022  |  Volume : 23  |  Issue : 2  |  Page : 111-115

Comparing the effectiveness of topical fluticasone 0.05% cream versus topical tacrolimus 0.1% ointment in pediatric atopic dermatitis: A randomized controlled trial


Department of Dermatology, Venereology and Leprology, PGIMER, Chandigarh, India

Date of Submission18-Nov-2021
Date of Decision06-Jan-2022
Date of Acceptance09-Jan-2022
Date of Web Publication30-Mar-2022

Correspondence Address:
Dr. Sanjeev Handa
Department of Dermatology, Venereology and Leprology, PGIMER, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.ijpd_158_21

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  Abstract 


Background: There is sparsity of data on the comparative effectiveness of topical steroids and topical tacrolimus in the treatment of pediatric atopic dermatitis (AD) and prevention of its relapse. Materials and Methods: Fifty eligible pediatric AD patients (with an objective SCORAD >40) were included in the study and were randomized into two groups of 25-those receiving topical fluticasone 0.05% cream twice daily and those receiving topical 0.1% tacrolimus ointment twice daily. All the patients were assessed at baseline and weeks 2, 4, and 6. At week 6, patients achieving >75% improvement were put on maintenance therapy of thrice weekly application of the respective drugs in each group and the patients were followed up at 10 and 14 weeks to observe for any flare of the disease. Results: The two treatment groups were similar at baseline. In the fluticasone group, 21 out of 25 patients (84%) achieved >75% improvement in SCORAD, while in the tacrolimus group, 17 out 25 patients (68%) achieved >75% improvement; P = 0.185]. Complete remission (100% improvement) was seen in 16 patients (64%) in the fluticasone group compared to 13 patients (52%) in the tacrolimus group at the end of 6 weeks (P = 0.38). The mean SCORAD values at 2, 4, and 6 weeks were compared between the 2 groups. The number of relapses was 1 in each group among patients on maintenance treatment. Conclusion: Both fluticasone cream and tacrolimus ointment are effective and safe for treatment of childhood AD, and for the prevention of AD flares.

Keywords: Atopic dermatitis, fluticasone, tacrolimus


How to cite this article:
Handa S, Chandrasegaran A, Kanwar AJ, Mahajan R. Comparing the effectiveness of topical fluticasone 0.05% cream versus topical tacrolimus 0.1% ointment in pediatric atopic dermatitis: A randomized controlled trial. Indian J Paediatr Dermatol 2022;23:111-5

How to cite this URL:
Handa S, Chandrasegaran A, Kanwar AJ, Mahajan R. Comparing the effectiveness of topical fluticasone 0.05% cream versus topical tacrolimus 0.1% ointment in pediatric atopic dermatitis: A randomized controlled trial. Indian J Paediatr Dermatol [serial online] 2022 [cited 2022 May 21];23:111-5. Available from: https://www.ijpd.in/text.asp?2022/23/2/111/341463




  Introduction Top


Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin condition characterized by itchy papules and occasionally vesicles, which become excoriated and often have a flexural distribution. The lesions may become lichenified over time. It is frequently associated with other atopic conditions in the individual or family members.[1],[2] Traditionally the treatment of AD includes the frequent use of emollients and intermittent use of topical corticosteroids to control acute flares.

Topical corticosteroids, although effective, may be associated with local and systemic adverse events, such as thinning of the skin and, in extreme cases, adrenal gland suppression. Two topical immunomodulators, pimecrolimus, and tacrolimus, provide alternatives to topical corticosteroids without these associated adverse events.[3],[4] They work by inhibiting calcineurin in the skin, which regulates the activity of several transcription factors that control cell division and trigger the early stages of T-cell activation. There are little data directly comparing moderately-potent topical corticosteroids with topical calcineurin inhibitors (TCIs), especially in pediatric AD. Hence, we aimed to compare the efficacy, number of flares, and adverse effect profile in children with mild to moderate AD, treated with topical fluticasone propionate 0.05% cream and topical tacrolimus 0.1% ointment.


  Materials and Methods Top


After obtaining permission from the institute's ethics committee (8310/PG-2Trg/2010/9815 dated on 12-08-2011), study subjects were recruited from the patients of the pediatric dermatology clinic at our institute over a period of one year. This was a prospective randomized, parallel group, double-blind study for a duration of 14 weeks.

Sample size

We wished to test whether the odds of an outcome in Group "A," pA (1−pA), are superior to the odds of the outcome in Ggroup "B," pB (1−pB), where pA and pB are the probabilities of the outcome in each group. Taking pA as 85% based on previous studies[5] and pB as 40.7% which was decided to be the minimum acceptable efficacy of drug in Group B,[6] and keeping the power of the test as 90%, α level as 5%, and the matching ratio as 1, sample size obtained was 23/group.

Of the screened patients, fifty patients were included in the study after obtaining consent from the parents or caregivers. Objective SCORAD was used to define the severity of AD. Inclusion criteria included patients of either sex with age between 1 and 12 years of age and mild to moderate AD (objective SCORAD up to 40). Exclusion criteria included the history of using systemic corticosteroids, nonsteroidal systemic immunosuppressants (e.g., cyclosporine, methotrexate), or phototherapy (UV-A and UV-B), within 4 weeks of initial study visit; history of using topical corticosteroids, TCIs, topical antibiotics or any medicated topical agent within 1 week before baseline; patients with severe AD (objective SCORAD >40); presence of major medical illness requiring systemic therapy including cancer; and a clinical diagnosis of active bacterial infections of the skin such as impetigo or abscess.

Evaluation and treatment schedule

All patients who met the eligibility criteria during the screening visit were randomized into two groups of 25, with patients receiving either topical fluticasone 0.05% cream or topical 0.1% tacrolimus ointment. All patients received antihistamines and emollients irrespective of their group. Patients developing secondary infections were treated with topical or systemic antibiotics as required. Detailed history regarding the duration and extent of the disease, family history, past treatment, aggravating/initiating factors, and clinical examination were recorded in a study form. All the patients were assessed at baseline and weeks 2, 4, 6, 10, and 14. The patients were instructed to apply the medicines twice daily for 6 weeks. At week 6, all patients were evaluated to assess the efficacy of the treatment. The primary efficacy parameter was the proportion of patients achieving more than 75% improvement in the SCORAD from baseline, at week 6 or earlier, in each group. The secondary efficacy parameter was the change in mean SCORAD between baseline and week 6. Patients achieving >75% improvement were put on maintenance therapy of thrice weekly application of the respective drugs in each group, and the patients were followed until 14 weeks and observed for any flare of the disease. The number of flares in each group was compared. Flare was defined as increase in the SCORAD index more than 50% above the score achieved at week 6. The cutaneous side effects were also assessed in the two groups in the induction as well as the maintenance phase.


  Results Top


Baseline data

Fifty-eight patients were screened, and fifty underwent randomization and all completed the study period. The two treatment groups were similar with respect to mean age, sex, duration of disease, age of onset, and objective SCORAD at baseline.

Efficacy evaluation

Primary efficacy outcome

There was no significant difference in efficacy between the groups, with a decrease in objective SCORAD from baseline to 6 weeks in both groups. In the fluticasone group, 21 out of 25 patients (84%) achieved >75% improvement in SCORAD, while in the tacrolimus group, 17 out 25 patients (68%) achieved >75% improvement [[Figure 1]; P = 0.185]. Complete remission (100% improvement) was seen in 16 patients (64%) in the fluticasone group compared to 13 patients (52%) in the tacrolimus group at the end of 6 weeks (P = 0.38).
Figure 1: Study flow-chart of patients in the two groups

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Secondary efficacy parameter

The mean SCORAD values at 2, 4 and 6 weeks were compared between the 2 groups [Figure 2], and the reduction in mean SCORAD was not significantly different between the groups [[Table 1]; P = 0.84 at 2 weeks; P = 0.37 at 4 weeks, and P = 0.22 at 6 weeks]. In the fluticasone group, the percentage reduction in mean SCORAD was 42.5% at 2 weeks, 73.4% at 4 weeks and 87.5% at 6 weeks. In the tacrolimus group, the percentage reduction in mean SCORAD was 43.8% at 2 weeks, 67.5% at 4 weeks, and 79.8% at 6 weeks.
Figure 2: Estimated marginal means of the two groups at weeks 2,4 and 6

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Table 1: Baseline data and treatment response of the study cohort

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Flares

The number of relapses was the same in each group (n = 1). In the fluticasone group, in one patient, there was an increase in SCORAD value from 0 at6 weeks to 14.8 at 10 weeks. In tacrolimus group in one patient, there was an increase in SCORAD from 4.5 6 weeks to 14.6 at 10 weeks. Both patients improved when they were re-initiated on twice daily application of respective therapy.

Adverse effects

Three patients in tacrolimus group complained of burning and two of the patients had associated redness which was mild and improved with time. There were no adverse effects reported in the fluticasone group.


  Discussion Top


In the treatment of pediatric AD, topical corticosteroids are the mainstay of treatment. Long-term corticosteroid application can lead to side effects such as skin atrophy, hypopigmentation, telangiectasias, adrenal suppression, and other adverse effects. TCIs are as effective as topical corticosteroids in the treatment of AD and are not associated with the adverse effects frequently encountered with steroids.[1]

Fluticasone 0.05% cream is a safe and effective treatment for childhood AD. It has been used safely in infants over 3 months of age.[7] It has a low potential for cutaneous adverse effects or HPA axis suppression even when applied over a large body surface area.[7] The efficacy of fluticasone cream in our study was slightly better than that observed by Wolkerstorfer et al.[8] (84% vs. 75%), possibly due to twice daily (vs. once daily) application of the drug or different treatment end points.

Only tacrolimus 0.03% ointment has been USFDA approved for the treatment of children aged 2–12 years, although tacrolimus 0.1% ointment has also shown efficacy and safety in children with AD. In one study where 0.03% ointment was evaluated in children <2 years of age over a period of 24 months, treatment was effective, well tolerated, and tacrolimus concentration in blood was <1 ng/ml in more than 98% of samples.[9] The most common adverse effects associated with tacrolimus have been local burning and pruritus. Similar results were found in another study by Patel et al. in children aged <2 years.[10] The efficacy of tacrolimus 0.1% ointment in our study was comparable to previous studies by Boguniewicz et al.[11] (68% vs. 67%). The proportion of patients obtaining >90% improvement with tacrolimus 0.1% ointment in our study was comparable to the study by Paller et al. (52% vs. 40.7%).[6] However, the treatment duration and scoring systems were different in the compared studies.

In this study, we compared the moderately-potent corticosteroid, fluticasone cream, with the calcineurin inhibitor, tacrolimus 0.1% ointment. The results of this study suggest comparable effectiveness in childhood AD. Both the drugs were similarly effective in preventing flares when used as thrice a week maintenance therapy up to 14 weeks. In a study comparing methylprednisolone acetate ointment once daily with tacrolimus 0.03% ointment twice daily in children and adolescents, both drugs were found to have similar efficacy.[12] In our study, tacrolimus was used in higher concentration (0.1%), the topical steroid was applied twice daily, and the results were compared with the above-mentioned study. Doss et al. noted the superiority of topical tacrolimus ointment over fluticasone ointment in one randomized controlled trial (RCT), and noninferiority in another RCT.[13],[14]

Hung et al. compared the effect of fluticasone or tacrolimus on Staphylococcus colonization in AD and concluded that topical anti-inflammatory therapy alone to improve the allergic skin inflammation of AD can reduce Staphylococcus aureus colonization of the skin.[15] In an RCT, Rubio-Gomis et al. studied the effect of fluticasone in mild to moderate AD relapse and showed that twice weekly fluticasone provides an effective maintenance treatment to control the risk of relapse in children with AD.[16] In a Cochrane systematic review, it was concluded that tacrolimus 0.1% was better than low-potency corticosteroids, pimecrolimus 1%, and tacrolimus 0.03%. Results were equivocal when comparing both dose formulations to moderate-to-potent corticosteroids.[17]

After treatment of an acute episode of AD, there are recurrent flares in most cases. There are two approaches to prevent flare in AD, either using only maintenance emollients or maintenance with emollients and intermittent applications of topical corticosteroids or TCIs. Many studies have proven that intermittent topical corticosteroids/TCIs are better than emollients with very little long-term toxicities.[18],[19],[20] Hanifin et al.[18] conducted a study in 348 patients (231 children and 117 adults) and showed that intermittent fluticasone cream (twice per week), in addition to regular daily emollients in the maintenance phase, were 7.7 times less likely to have an AD relapse than subjects receiving intermittent vehicle cream and emollients. Intermittent application of tacrolimus also has been proven to be more efficacious than emollient alone. Wollenberg et al.[19] and Paller et al.[20] found that twice weekly or thrice weekly tacrolimus was significantly better than vehicle in controlling AD flares.

Schmitt et al. did a systematic review of eight RCTs reporting efficacy of topical corticosteroids and/or TCIs for flare prevention in AD.[21] These trials evaluated proactive therapy with topical tacrolimus, fluticasone propionate, and methylprednisolone acetate. Each agent under study was more effective than vehicle at flare prevention. Meta-analysis suggested that topical fluticasone propionate (Relative risk [RR] 0.46, 95% Confidence interval [(CI] 0.38–0.55) may be more efficacious to prevent disease flares than topical tacrolimus (RR 0.78, 95% CI 0.60–1.00). Such superiority could not be found in our study.

There are few trials directly comparing topical corticosteroids and calcineurin inhibitors in the prevention of AD flares. However, it can be inferred from our study that both fluticasone and tacrolimus are equally effective for short-term maintenance therapy to prevent AD flares. These have also been found to have relatively negligible toxicity even with long-term use.[21] The major limitations of the present study are a smaller sample size and shorter follow-up period which needs to be replicated in a larger multicentric study. The blood levels of tacrolimus could not be measured, and serum cortisol levels were not monitored to investigate HPA axis suppression by fluticasone.


  Conclusion Top


Fluticasone and tacrolimus are similarly effective for the treatment of childhood AD. They are also effective in intermittent doses for the prevention of AD flares. The adverse effects are minimal, and they are safe in children. Topical tacrolimus monotherapy is a reasonable alternative particularly in children.

Declaration of consent

The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s) of the patient. In the form the parent(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: Part II. J Eur Acad Dermatol Venereol 2018;32:850-78.  Back to cited text no. 1
    
2.
Möhrenschlager M, Darsow U, Schnopp C, Ring J. Atopic eczema: What's new? J Eur Acad Dermatol Venereol 2006;20:503-11, 513.  Back to cited text no. 2
    
3.
Williams HC. Epidemiology of atopic dermatitis. Clin Exp Dermatol 2000;25:522-9.  Back to cited text no. 3
    
4.
Alomar A, Berth-Jones J, Bos JD, Giannetti A, Reitamo S, Ruzicka T, et al. The role of topical calcineurin inhibitors in atopic dermatitis. Br J Dermatol 2004;151 Suppl 70:3-27.  Back to cited text no. 4
    
5.
Bleehen SS, Chu AC, Hamann I, Holden C, Hunter JA, Marks R. Fluticasone propionate 0.05% cream in the treatment of atopic eczema: A multicentre study comparing once-daily treatment and once-daily vehicle cream application versus twice-daily treatment. Br J Dermatol 1995;133:592-7.  Back to cited text no. 5
    
6.
Paller A, Eichenfield LF, Leung DY, Stewart D, Appell M. A 12-week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients. J Am Acad Dermatol 2001;44:S47-57.  Back to cited text no. 6
    
7.
Friedlander SF, Hebert AA, Allen DB; Fluticasone Pediatrics Safety Study Group. Safety of fluticasone propionate cream 0.05% for the treatment of severe and extensive atopic dermatitis in children as young as 3 months. J Am Acad Dermatol 2002;46:387-93.  Back to cited text no. 7
    
8.
Wolkerstorfer A, Strobos MA, Glazenburg EJ, Mulder PG, Oranje AP. Fluticasone propionate 0.05% cream once daily versus clobetasone butyrate 0.05% cream twice daily in children with atopic dermatitis. J Am Acad Dermatol 1998;39:226-31.  Back to cited text no. 8
    
9.
Mandelin JM, Rubins A, Remitz A, Cirule K, Dickinson J, Ho V, et al. Long-term efficacy and tolerability of tacrolimus 0.03% ointment in infants:* A two-year open-label study. Int J Dermatol 2012;51:104-10.  Back to cited text no. 9
    
10.
Patel RR, Vander Straten MR, Korman NJ. The safety and efficacy of tacrolimus therapy in patients younger than 2 years with atopic dermatitis. Arch Dermatol 2003;139:1184-6.  Back to cited text no. 10
    
11.
Boguniewicz M, Fiedler VC, Raimer S, Lawrence ID, Leung DY, Hanifin JM. A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric tacrolimus study group. J Allergy Clin Immunol 1998;102:637-44.  Back to cited text no. 11
    
12.
Bieber T, Vick K, Fölster-Holst R, Belloni-Fortina A, Städtler G, Worm M, et al. Efficacy and safety of methylprednisolone aceponate ointment 0.1% compared to tacrolimus 0.03% in children and adolescents with an acute flare of severe atopic dermatitis. Allergy 2007;62:184-9.  Back to cited text no. 12
    
13.
Doss N, Reitamo S, Dubertret L, Fekete GL, Kamoun MR, Lahfa M, et al. Superiority of tacrolimus 0.1% ointment compared with fluticasone 0.005% in adults with moderate to severe atopic dermatitis of the face: Results from a randomized, double-blind trial. Br J Dermatol 2009;161:427-34.  Back to cited text no. 13
    
14.
Doss N, Kamoun MR, Dubertret L, Cambazard F, Remitz A, Lahfa M, et al. Efficacy of tacrolimus 0.03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: Evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0.005% ointment. Pediatr Allergy Immunol 2010;21:321-9.  Back to cited text no. 14
    
15.
Hung SH, Lin YT, Chu CY, Lee CC, Liang TC, Yang YH, et al. Staphylococcus colonization in atopic dermatitis treated with fluticasone or tacrolimus with or without antibiotics. Ann Allergy Asthma Immunol 2007;98:51-6.  Back to cited text no. 15
    
16.
Rubio-Gomis E, Martinez-Mir I, Morales-Olivas FJ, Martorell-Aragones A, Palop-Larrea V, Bernalte-Sesé A, et al. Fluticasone in mild to moderate atopic dermatitis relapse: A randomized controlled trial. Allergol Immunopathol (Madr) 2018;46:378-84.  Back to cited text no. 16
    
17.
Cury Martins J, Martins C, Aoki V, Gois AF, Ishii HA, da Silva EM. Topical tacrolimus for atopic dermatitis. Cochrane Database Syst Rev 2015;2015:CD009864.  Back to cited text no. 17
    
18.
Hanifin J, Gupta AK, Rajagopalan R. Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients. Br J Dermatol 2002;147:528-37.  Back to cited text no. 18
    
19.
Wollenberg A, Reitamo S, Atzori F, Lahfa M, Ruzicka T, Healy E, et al. Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Allergy 2008;63:742-50.  Back to cited text no. 19
    
20.
Paller AS, Eichenfield LF, Kirsner RS, Shull T, Jaracz E, Simpson EL, et al. Three times weekly tacrolimus ointment reduces relapse in stabilized atopic dermatitis: A new paradigm for use. Pediatrics 2008;122:e1210-8.  Back to cited text no. 20
    
21.
Schmitt J, von Kobyletzki L, Svensson A, Apfelbacher C. Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema: Systematic review and meta-analysis of randomized controlled trials. Br J Dermatol 2011;164:415-28.  Back to cited text no. 21
    


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