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

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

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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  • 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

  • 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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  • 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

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

25. Rx files: topical corticosteroids: comparison chart., accessed June 28-2023

Authors do not have any conflicts of interest to declare.