Management of acne

,

Applied Evidence

Management of acne

J Fam Pract. 2003 January;52(1):43-51

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References

1. Thiboutot DM. An overview of acne and its treatment. Cutis 1996;57:8-12.

2. Leyden JJ. Therapy for acne vulgaris. N Engl J Med 1997;336:1156-62.

3. Issued by funding/sponsoring agency: Management of Acne Volume 1: Evidence Report and Appendixes. Rockville, Md: Dept. of Health and Human Services (US), Public Health Service; 2001 Sep. Report No.: 01-E019. Issued by performing agency: Lehmann HP, Andrews JS, Robinson KA, Holloway VL, Goodman SN. Johns Hopkins Evidence-based Practice Center. Contract No.: 290-97-006. Sponsored by the Agency for Healthcare Research and Quality.

4. Eady EA, Burke BM, Pulling K, Cunliffe WJ. The benefit of 2% salicylic acid lotion in acne—A placebo-controlled study. J Dermatol Treat 1996;7:93-6.

5. Basset OB, Pannowitz DL, Barnetson RS. A comparative study of tea-tree oil versus benzoyl peroxide in the treatment of acne. Med J Aust 1990;153:455-8.

6. Hughes BR, Norris JF, Cunliffe WJ. A double-blind evaluation of topical isotretinoin 0.05%, benzoyl peroxide gel 5% and placebo in patients with acne. Clin Exp Dermatol 1992;17:165-8.

7. Ede M. A double-blind, comparative study of benzoyl peroxide, benzoyl peroxide-chlorhydroxyquinoline, benzoyl peroxide-chlorhydroxyquinolone-hydrocortisone, and placebo lotions in acne. Curr Ther Res Clin Exp 1973;15:624-9.

8. Mills OH, Jr, Kligman AM, Pochi P, Comite H. Comparing 2.5%, 5%, and 10% benzoyl peroxide on inflammatory acne vulgaris. Int J Dermatol 1986;25:664-7.

9. Pedace FJ, Stoughton R. Topical retinoic acid in acne vulgaris. Br J Dermatol 1971;84:465-9.

10. Christiansen JV, Gadborg E, Ludvigsen K, et al. Topical tretinoin, vitamin A acid (Airol) in acne vulgaris. A controlled clinical trial. Dermatologica 1974;148:82-9.

11. Berson DS, Shalita AR. The treatment of acne: the role of combination therapies. J Am Acad Dermatol 1995;32:531-41.

12. Shalita A, Weiss JS, Chalker DK, et al. A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris: a multicenter trial. J Am Acad Dermatol 1996;34:482-5.

13. Cunliffe W, Caputo R, Dreno B, et al. Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S.multicenter trials. J Am Acad Dermatol 1997;36:S126-34.

14. Galvin SA, Gilbert R, Baker M, et al. Comparative tolerance of adapalene 0.1% gel and six different tretinoin formulations. Br J Dermatol 1998;139:S34-40.

15. Clucas A, Verschoore M, Sorba V, et al. Adapalene 0.1% gel is better tolerated than tretinoin 0.025% gel in acne patients. J Am Acad Dermatol 1997;36:S116-8.

16. Cavicchini S, Caputo R. Long-term treatment of acne with 20% azelaic acid cream. Acta Derm Venereol Suppl. 1989;143:40-4.

17. Katsambas A, Graupe K, Stratigos J. Clinical studies of 20% azelaic cream in the treatment of acne vulgaris. Comparison with vehicle and topical tretinoin. Acta Derm Venereol Suppl 1989;143:35-9.

18. Shalita AR, Chalker DK, Griffith RF, et al. Tazarotene gel is safe and effective in the treatment of acne vulgaris: a multicenter, double blind, vehicle-controlled study. Cutis 1999;63:349-53.

19. Becker LE, Bergstresser PR, Whiting DA, et al. Topical clindamycin therapy for acne vulgaris. A cooperative clinical study Arch Dermatol 1981;117:482-5.

20. Ellis CN, Gammon WR, Stone DZ, Heezen-Wehner JL. A comparison of Cleocin T Solution, Cleocin T Gel, and placebo in the treatment of acne vulgaris. Cutis 1988;42:245-7.

21. Pochi PE, Bagatell FK, Ellis CN, et al. Erythromycin 2 percent gel in the treatment of acne vulgaris. Cutis 1988;41:132-6.

22. Lesher JL, Jr, Chalker DK, Smith JG, Jr, et al. An evaluation of a 2% erythromycin ointment in the topical therapy of acne vulgaris. J Am Acad Dermatol 1985;12:526-31.

23. Dobson RL, Belknap BS. Topical erythromycin solution in acne. Results of a multiclinic trial. J Am Acad Dermatol 1980;3:478-82.

24. Leyden JJ, Shalita AR, Saatjian GD, Sefton J. Erythromycin 2% gel in comparison with clindamycin phosphate 1% solution in acne vulgaris. J Am Acad Dermatol 1987;16:822-7.

25. Shalita AR, Smith EB, Bauer E. Topical erythromycin v clindamycin therapy for acne. A multicenter, double-blind comparison. Arch Dermatol 1984;120:351-5.

26. Lookingbill DP, Chalker DK, Lindholm JS, et al. Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: combined results of two double-blind investigations. J Am Acad Dermatol 1997;37:590-5.

27. Sykes NL, Webster GF. Acne: a review of optimum treatment. Drugs 1994;48:59-70.

28. Gammon WR, Meyer C, Lantis S, et al. Comparative efficacy of oral erythromycin versus oral tetracycline in the treatment of acne vulgaris. A double-blind study. J Am Acad Dermatol 1986;14:183-6.

29. Eady EA, Jones CE, Tipper JL, et al. Antibiotic resistant Propionibacteria in acne: need for policies to modify antibiotic usage. Br Med J 1993;306:555-6.

30. McEvoy GK, editor. AHFS Drug Information. Bethesda, Md: American Society of Health System Pharmacists; 1996.

31. Blaney DJ, Cook CH. Topical use of tetracycline in the treatment of acne: a double-blind study comparing topical and oral tetracycline therapy and placebo. Arch Dermatol 1976;112:971-3.

32. Lane P, Williamson DM. Treatment of acne vulgaris with tetracycline hydrochloride: a double-blind trial with 51 patients. Br Med J 1969;2:76-9.

33. Wong RC, Kang S, Heezen JL, et al. Oral ibuprofen and tetracycline for the treatment of acne vulgaris. J Am Acad Dermatol 1984;11:1076-81.

34. Plewig G, Petrozzi JW, Berendes U. Double-blind study of doxycycline in acne vulgaris. Arch Dermatol 1970;101:435-8.

35. Shapiro LE, Knowles SR, Shear NH. Comparative safety of tetracycline, minocycline, and doxycycline. Arch Dermatol 1997;133:1224-30.

36. Garner SE, Eady EA, Popescu C, Newton J, Li Wan Po A. Minocycline for acne vulgaris: efficacy and safety (Cochrane Review). In: The Cochrane Library., Issue 4, 2001.

37. Lucky AW. Hormonal correlates of acne and hirsutism. Am J Med 1995;98:89S-94S.

38. Lucky AW, Henderson TA, Olson WH, et al. Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris. J Am Acad Dermatol 1997;37:746-54.

39. Peck GL, Olsen TG, Butkus D, et al. Isotretinoin versus placebo in the treatment of cystic acne. A randomized double-blind study. J Am Acad Dermatol 1982;6:735-45.

40. Hanson N, Leachman S. Safety Issues in Isotretinoin Therapy. Semin Cutan Med Surg 2001;20:166-83.

41. Layton AM, Knaggs H, Taylor J, Cunliffe WJ. Isotretinoin for acne vulgaris—10 years later: a safe and successful treatment. Br J Dermatol 1993;129:292-6.

42. Accutane prescribing information. Nutley, N.J.: Roche Pharmaceuticals, 1998.

43. Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, et al. Retinoic acid embryopathy. N Engl J Med 1985;313:837-41.

44. Helms SE, Bredle DL, Zajic J, et al. Oral contraceptive failure rates and oral antibiotics. J Am Acad Dermatol 1997;36:705-10.

Adapalene (Differin) is a synthetic naphthoic acid derivative with retinoid activity. Several large, randomized studies have shown that adapalene gel 0.1% and tretinoin concentrations ranging from 0.025% to 0.1% were comparable in reducing total lesion counts by 50% in 4 to 12 weeks (SOR: A).^12-14 One trial found that adapalene 0.1% produced a statistically significant reduction greater than that with tretinoin 0.025% in both noninflammatory and inflammatory lesions at 12 weeks (SOR: A).¹² Adapalene was also significantly better tolerated than tretinoin, as evidenced by less erythema, scaling, and dryness.^12,15 Thus far, there have been no significant studies comparing adapalene to other topical agents such as benzoyl peroxide.

Azelaic acid (Azelex) is a dicarboxylic acid that possesses bacteriostatic properties and is structurally unrelated to any of the conventional acne therapies. In a single-blind trial of 309 patients comparing 20% AZA with 5% benzoyl peroxide and placebo, AZA yielded a significant decrease in papulo-pustular lesion counts by 35% compared with placebo. There was equivalent efficacy between AZA and benzoyl peroxide (SOR: B).¹⁶ Patients tolerated AZA better than benzoyl peroxide, with 9% of AZA recipients reporting a burning sensation that subsided after 2 weeks, and 15% of the benzoyl peroxide group reporting local side effects. In another controlled comparison, 20% AZA cream used twice daily for 5 to 6 months was comparable in efficacy to 0.05% tretinoin cream for patients with comedonal acne but statistically more effective in reducing the number of papules (SOR: B).¹⁷ Tretinoin caused significantly more erythema and scaling than did AZA.

Tazarotene (Tazorac) is the first of a family of receptor-selective acetylenic retinoids. In a multicenter, randomized controlled trial including 334 patients, tazarotene 0.1% and 0.05%, applied once daily for mild-to-moderate acne significantly reduced noninflammatory acne and total lesion counts when compared with placebo at 4 to 8 weeks (SOR: B).¹⁸ The 0.1% gel also significantly reduced inflammatory lesions at 12 weeks. Adverse effects were dose related, ranging from 5% to 13% and included erythema and burning. There are no published trials comparing tazarotene with other retinoids or benzoyl peroxide. Tazarotene is 30% to 70% more expensive than comparable topical agents such as tretinoin, benzoyl peroxide, and antibiotics.

FIGURE
Treatment of acne according to type and severity

TABLE 4
Medication options for acne vulgaris

Evidence Strength*	Medication	Cost per month**	Relative efficacy	Comparator	Comment
Comedonal, papulopustular, or nodulocystic
A	Norgestimate/ethinyl estradiol	$31.08	>	Placebo	Decreases comedone and inflammatory lesion counts
Comedonal or papulopustular
A	Adapalene	$34.47 (gel)	=	Tretinoin	Adapalene has better side-effect profile
A	Benzoyl peroxide	$7.99–$16.19	>	Placebo	Price depends on generic vs brand, not concentration
A	Clindamycin	$34.73 (gel)	>	Placebo	Topical
A	Erythromycin	$18.31 (gel)	>	Placebo	Topical
A or B	Tretinoin	$23.91	>	Placebo	Evidence strength A for noninflammatory and B for inflammatory
B	Azelaic acid	$44.40	>	Placebo	Topical
B	Azelaic acid	$44.40	=	Benzoyl peroxide	Azelaic acid has better side-effect profile
B	Azelaic acid	$44.40	=	Tretinoin	Azelaic acid has better side-effect profile
B	Clindamycin	$34.73	=	Erythromycin	Topical
B	Clindamycin	$34.73	=	Benzoyl peroxide	Topical
B	Salicylic Acid		>	Placebo	Topical
B	Tazarotene	$64.75 (.05%) $68.74 (0.1%)	>	Placebo	Side effects similar to those of topical retinoids
B	Tretinoin	$23.91	>	Benzoyl peroxide	Tretinoin: stronger effect on comedones; BPO: stronger effect on papules
Papulopustular or nodulocystic
A	Tetracycline	$8.38	>	Placebo	Oral
B	Doxycycline	$24.82	>	Placebo	Oral
B	Erythromycin	$27.15	=	Tetracycline	Oral. Higher resistance levels of P acnes to erythromycin
B	Minocycline	$21.90	>	Placebo	Oral
B	Minocycline	$21.90	=	Tetracycline	Oral
KEY: > is more effective than; < is less effective than; = is equivalent to.
*Evidence Strength:
A = At least two trials of acceptable quality showing moderate to strong statistical evidence for clinically meaningful endpoint and effect.
B = Evidence is of modest strength, such as when only one trial addresses a comparison, there is significant heterogeneity, large differences are not statistically significant, or poor trial quality prevents accepting strong statistical evidence at face value.
**Cost: Referenced from a major on-line retail pharmacy.

Topical antibiotics

Topical antibiotics are effective in the treatment of mild-to-moderate inflammatory acne by reducing the population of P acnes in sebaceous follicles and by suppressing chemotaxis.¹¹ Several large randomized controlled trials demonstrated that topical clindamycin 1% and topical erythromycin 2% applied twice daily were consistently superior to placebo in reducing the number of papules and pustules in patients with moderate-to-severe acne (SOR: A).^19-23 Erythema and peeling were rare, comparable to that seen with placebo. Moreover, a randomized trial of 102 patients comparing 1% clindamycin with 2% erythromycin demonstrated that both medications significantly reduced the number of papules and comedones with no significant differences between the two (SOR: B).^24,25 Furthermore, in two double-blind, randomized trials involving 334 patients, a combination gel containing clindamycin 1% and benzoyl peroxide 5% proved superior to each component alone in reducing inflammatory lesions, and superior to the clindamycin-only gel in reducing noninflammatory lesions (SOR: B).²⁶ Trial data on the combination gel containing erythromycin 3% and benzoyl peroxide 5% are of poor quality; thus the same conclusion cannot be made.

Oral antibiotics

Oral antibiotics are most often used for moderate-to-severe inflammatory acne. They work by suppressing P acnes growth, thereby reducing the production of inflammatory mediators.²⁷ However, as systemicagents, they cause more significant and diverse side effects than do topical agents. Unfortunately there are no head-to-head trials comparing different oral antibiotics, or comparing oral and topical antibiotics.