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#345 Fancy Creams for Scaly Skin: Topical calcineurin inhibitors for atopic dermatitis (Free)


CLINICAL QUESTION
What are the risks and benefits of topical calcineurin inhibitors for atopic dermatitis?

BOTTOM LINE
For improvement of atopic dermatitis, tacrolimus 0.1% is at least equivalent to moderate-potency topical corticosteroids. Pimecrolimus 1% is better than placebo, but likely inferior to tacrolimus 0.1% and moderate potency corticosteroids. Burning skin sensation is common early (30-50% of users) but tapers off for most (<10% at 6 months).


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EVIDENCE
  • Results statistically different unless stated.
  • 4 systematic reviews with meta-analyses in past 10 years.1-4
  • Versus vehicle/low potency topical corticosteroids:
    • Tacrolimus 0.1% (2 RCTs, 460 patients) improved atopic dermatitis for 48-67% versus 16-38% with vehicle/hydrocortisone acetate 1%, number needed to treat (NNT)=3-4 at 3 weeks.5-6
      • Other RCT showed similar.7
    • Pimecrolimus 1% (meta-analysis: 8 RCTs, 2298 patients) improved atopic dermatitis for 44% versus 22% with vehicle, NNT=5 at 6 weeks.1
  • Versus moderate/high potency topical corticosteroids:
    • Tacrolimus 0.1% in:
      • 2 RCTs (1540 patients) improved atopic dermatitis for 73-93% versus 52-88% for corticosteroids at 3-12 weeks.8,9 Other RCT showed similar.10
      • 4 RCTs (513 patients) found no difference at 2 weeks-11 months.11-14
    • Pimecrolimus 1% in:
      • 1 RCT (2418 patients) found no difference at 3 weeks.15
      • 2 RCTs (745 patients) improved atopic dermatitis for 37-53% versus 68-88% with corticosteroids at 3 weeks. Corticosteroids superior, NNT=3-4.16,17
  • Tacrolimus 0.1% versus Pimecrolimus 1%:
    • Meta-analysis (3 RCTs, 543 patients),2 good response: 35% tacrolimus versus 19% pimecrolimus at 2-6 weeks, NNT=7.
    • Network meta-analysis: No difference.18
  • Adverse effects calcineurin inhibitors versus topical corticosteroids (3-52 weeks):2
    • Skin burning: 30% versus 9%, number needed to harm=4.
    • Skin atrophy: 0% versus 0.8%, not significant.
  • Limitations: Most RCTs funded by manufacturers.2
CONTEXT
  • Tacrolimus 0.1% superior to tacrolimus 0.03% with similar side effects.2
  • Pimecrolimus 1% (cream) approved for patients >3 months old,19 tacrolimus 0.1% (ointment) for patients>15 years old.20
  • Application site reactions (skin burning, pruritus): Usually transient. Example, tacrolimus 0.1% skin burning: 51% (week 1), 17% (week 2), 7% (month 6).8
  • Inconsistent association between calcineurin inhibitors and lymphoma.21-23
    • Health Canada warning removed 2021.24
  • Cost (30 grams):25 Tacrolimus 0.1% ~$103, betamethasone valerate 0.1% ~$13.

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Author(s):

  • Emelie Braschi MD CCFP PhD
  • Samantha Moe PharmD

1. Akhtar SE, Shakil S, Farooqui SK, et al. Ann Med Surg. DOI:10.1097/MS9.0000000000000844, epub ahead of print. May 23, 2023.

2. Martins JC, Martins C, Aoki V et al. Cochrane Database Syst Rev. 2015 (7):CD009864.

3. Abędź N, Pawliczak R. Postepy Dermatol Alergol. 2019 Dec; 36(6):752-759.

4. Broeders JA, Ali AU, Fischer G et al. J Am Acad Dermatol. 2016 Aug; 75(2):410-419.e3.

5. Reitamo S, Van Leent EJM, Ho V et al. J Allergy Clin Immunol. 2002 Mar; 109(3):539-46.

6. Boguniewicz M, Fiedler VC, Raimer S et al. J Allergy Clin Immunol. 1998 Oct; 102(4 Pt 1):637-44.

7. Ruzicka T, Bieber T, Schopf E et al. N Engl J Med. 1997; 337(12):816-21.

8. Reitamo S, Ortonne JP, Sand C et al. Br J Dermatol. 2005 Jun; 152(6):1282-9.

9. Doss N, Reitamo S, Dubertret L et al. Br J Dermatol. 2009 Aug; 161(2):427-34.

10. Caproni M, Torchia D, Antiga E et al. Br J Dermatol. 2007 Feb; 156(2):312-9.

11. Reitamo S, Rustin M, Ruzicka T et al. J Allergy Clin Immunol. 2002 Mar; 109(3):547-55.

12. Mandelin J, Remitz A, Virtanen H et al. Acta Derm Venereol. 2010 Mar; 90(2):170-4.

13. Schnopp C, Remling R, Mohrenschlager M et al. J Am Acad Dermatol. 2002 Jan; 46(1):73-7.

14. Neumann E, Amtage D, Bruckner-Tuderman L et al. J Dtsch Dermatol Ges. 2008 Jul; 6(7):548-53.

15. Sigurgeirsson B, Boznanski A, Todd G et al. Pediatrics. 2015; 135:597-606.

16. Luger TA, Lahfa M, Folster-Holst R et al. J Dermatolog Treat. 2004:15, 169–178.

17. Luger T, Van Leent EJ, Graeber M et al. Br J Dermatol. 2001 Apr; 144(4):788-94.

18. Huang X, Xu B. Dermatology. 2015; 231(1):41-9.

19. Bausch Health Inc. Canada. Elidel® Product Monograph. Available at https://bauschhealth.ca/.

20. LEO Pharma Inc. Canada. Protopic® Product Monograph. Available at www.leo-pharma.ca, accessed June 28-2023.

21. Wu PC, Huang IH, Liu CW et al. J Dtsch Dermatol Ges. 2021 Sep; 19(9):1265-1269.

22. Lam M, Zhu JW, Tadrous M et al. JAMA Dermatol. 2021 May 1; 157(5):549-558.

23. Devasenapathy N, Chu A, Wong M et al. Lancet Child Adolesc Health. 2023 Jan; 7(1):13-25

24. LEO Pharma Inc. Canada. The product monograph for Protopic® has been updated. Available at www.leo-pharma.ca, accessed June 28-2023.

25. Rx files: topical corticosteroids: comparison chart. https://www.rxfiles.ca/rxfiles/, accessed June 28-2023

Authors do not have any conflicts of interest to declare.