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Isotretinoin and antibiotics’ role in the treatment of acne vulgaris
By: Grant Jerkovich, Ben Gardner, Jake Felckowski, Bre May
Outline
◼ Antibiotics and Acne▪ Resistance▪ Role in therapy
◼ Acne in Society▪ Mental Health Comorbidities▪ Cost to society
◼ Isotretinoin: The Facts▪ Side Effects▪ Efficacy
◼ Isotretinoin: surrounding controversy▪ Litigation▪ Link to Irritable Bowel Disease (IBD)
Antibiotics and acne
◼ https://www.aad.org/practicecenter/quality/clinical-guidelines/acne▪ Extremely comprehensive PDF of accepted guidelines
◼ Global Alliance to Improve Outcomes in Acne. Antibiotic stewardship in dermatology: limiting antibiotic use in acne. PubMed PMID: 24721547.▪ Indication/recommendations versus actual usage
Resistance
◼ Andersson, D. I. & Hughes, D. (2010). Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol 8, 260– 271.
◼ Björkman J, Hughes D, Andersson DI. Virulence of antibiotic-resistant
Microbiome
◼ Jernberg, Cecilia, et al. "Long-term impacts of
antibiotic exposure on the human intestinal
microbiota." Microbiology 156.11 (2010): 3216-3223.
◼ Jakobsson, H. E., Jernberg, C., Andersson, A. F., Sjo¨
lund-Karlsson, M., Jansson, J. K. & Engstrand, L.
(2010). Short-term antibiotic treatment has differing
long-term impacts on the human throat and gut
microbiome. PLoS ONE 5, e9836.
Current Role in therapy
◼ Prevention of scarring◼ Treat until it resolves on its own◼ https://www.aad.org/practicecente
r/quality/clinical-guidelines/acne◼ Chon SY, Doan HQ, Mays RM:
Antibiotic overuse and resistance in
dermatology. Dermatologic
Therapy, 25: 55–69.
Anxiety, Depression and Suicidal Ideation
◼ “No evidence that use of isotretinoin is associated with an
increased risk for depression, suicide, or other psychiatric
disorders.”
◼ S.S. Jick, H.M. Kremers, C. Vasilakis-Scaramozza | Isotretinoin
use and risk of depression, psychotic symptoms, suicide, and
attempted suicide | Arch Dermatol, 136 (2000), pp. 1231–1236
◼ A.L. Marqueling, L.T. Zane | Depression and suicidal behavior in
acne patients treated with isotretinoin: a systematic review |
Semin Cutan Med Surg, 26 (2007), pp. 210–220
◼ Studies actually found less depressive symptoms after use of
isotretinoin
◼ Insufficient data to correlate suicidal ideation with the use of
Isotretinoin.
Dollar Cost to Society
◼ D. Bickers, T. Dall, E. Faulkner, E. Gemmen, C. Goodman, C. Gould, H. Lim, D. Margolis, M. Weinstock. “The burden of skin diseases: 2004: A joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology.” J Am Acad Dermatol. 2006 Sep;55(3):490-500.
◼ Total Direct Cost of Acne (cystic and vulgaris) in 2004: $2500 million
◼ Indirect Costs: $619 Million
◼ Total: $3,119 million
Side Effects
◼ Side effects that have an occurrence rate >5% ▪ dry lips, dry skin, back pain, dry eye, arthralgia, epistaxis,
headache, nasopharyngitis, dermatitis, blood creatine kinase increased, chelitis, musculoskeletal discomfort, upper respiratory tract infection, visual acuity reduced
Side Effects
◼Many side effects are dose dependent and are reversible upon discontinuation
◼Lasting side effects include:▪ Dermatological dryness▪ Mucosal dryness
Goulden V, Layton AM, Cunliffe WJ. Long-term safety of isotretinoin as a treatment for acne vulgaris. Br J Dermatol. 1994;131:360–3
Side Effects
◼Elevation of lipoproteins and hepatic enzymes▪ Direct correlation between dose and elevation▪ Elevation is returned to baseline upon
discontinuation
Zane LT, Leyden WA, Marqueling AL, et al. A population-based analysis of laboratory abnormalities during isotretinoin therapy for acne vulgaris. Arch Dermatol. 2006;142:1016-1022
Side Effects
◼Teratogenicity:▪ iPLEDGE: Restricted distribution system to
prevent fetal exposure
Side Effects
◼Critiques of iPLEDGE:▪ Persuasion of implantable/IUD contraceptives ▪ Revision of materials to more user friendly versions▪ Reduction of commitments for men and women non-
childbearing age
Side Effects
◼Teratogenicity:
Efficacy
Vallerand, I. A., Lewinson, R. T., Farris, M. S., Sibley, C. D., Ramien, M. L., Bulloch, A. G., & Patten, S. B. (2017). Efficacy and Adverse Events of Oral Isotretinoin for Acne: A Systematic Review. British Journal of Dermatology. doi:10.1111/bjd.15668
Isotretinoin: Litigation
-Early 2000’s: Lawsuits against Roche Pharmaceuticals begin to surface. Allegations of link to IBD.
-February 2002: Roche’s patent for isotretinoin expires. Generic manufacture of isotretinoin begins.
-June 2009: Roche discontinues manufacture and distribution of Accutane, citing “low market-share, high cost of defending personal injury lawsuits.”
Isotretinoin: LitigationDisproportionate reporting by attorneys
◼ Cases reported to FAERS (2003-2011) queried for IBD + tretinoin use.
◼ 2,214 cases of IBD “resulting from isotretinoin.”
▪ Attorneys: 1,944 (87.8%)
▪ Physicians: 132 (6.0%)
▪ Consumers: 112 (5.1%)
Isotretinoin: Link to IBD
◼ IBD occurrence rate low. Clinical trials not well suited to study potential link.
◼ “Isotretinoin Is Not Associated With Inflammatory Bowel Disease: A Population-Based Case–Control Study” was published in The American Journal of Gastroenterology on July 21, 2009.
Isotretinoin: Link to IBD
◼ Results: 1.2 % of IBD cases used isotretinoin before IBD diagnosis, which was statistically similar to controls (1.1 %users). This was also similar to the number of IBD patients who used isotretinoin after a diagnosis of IBD (1.1 % ).
Conclusion
◼ Antibiotics do not provide a sustainable treatment for acne vulgaris. Resistance and alteration of the microbiome are concerning.
◼ Acne vulgaris is a disease with high societal costs that warrants effective treatment.
◼ Isotretinoin is a highly effective treatment, but its use must be effectively regulated to avoid fetal exposure.
◼ Isotretinoin has been putatively associated with IBD, but meta-analysis has not proven a link.
