Isotretinoin use for acne in obese and overweight young people: A retrospective study
Authors: Maggie Tallmadge, Ashaki Patel, Melodee Nugent Liegl, Amy Pan, Jody Barbeau, Leah Lalor
Journal: Journal of the American Academy of Dermatology (2021)

To the Editor: The response of obese and overweight young people to isotretinoin is understudied. This study compares isotretinoin treatment for acne in overweight and obese young people with their normal-weight peers to evaluate whether current dosing strategies (0.5-1 mg/kg/day for 120-150 mg/kg cumulative dose) are appropriate.1Zaenglein A.L. Pathy A.L. Schlosser B.J. et al.Guidelines of care for the management of acne vulgaris.J Am Acad Dermatol. 2016; 74: 945-973.e33https://doi.org/10.1016/j.jaad.2015.12.037Abstract Full Text Full Text PDF PubMed Scopus (700) Google Scholar We hypothesize that young people with a higher body mass index (BMI) may be effectively underdosed due to physicians' reluctance to prescribe higher daily doses of isotretinoin, potentially prolonging the treatment and impacting side effects. We hypothesize that there will be differences in daily dose (mg/kg), treatment length, and side effect incidence among the groups.A retrospective chart review was conducted on patients aged 10 to 24 years from 1 academic center who completed at least 2 months of isotretinoin therapy for acne from November 1, 2012, to October 31, 2019. The BMI was calculated for each patient. Centers for Disease Control growth charts were used to compute BMI percentiles and sort patients into BMI groups, as is the standard in pediatrics.Of the 550 patients eligible for analysis, 367 (67%) were normal weight or underweight, 101 (18%) were overweight, and 82 (14.9%) were obese (Table I). Overweight and obese patients had lower daily doses (mg/kg) than other participants during the first 2 months of treatment, although all fell in the 0.5 to 1.0 mg/kg/day range (P ≤ .001). Although alanine aminotransferase and triglyceride levels increased significantly as the BMI increased, only 1 instance of triglyceride elevation was clinically meaningful.2Barbieri J.S. Shin D.B. Wang S. Margolis D.J. Takeshita J. The clinical utility of laboratory monitoring during isotretinoin therapy for acne and changes to monitoring practices over time.J Am Acad Dermatol. 2020; 82: 72-79https://doi.org/10.1016/j.jaad.2019.06.025Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Table II summarizes the treatment outcomes. Headaches were the only complication that differed significantly: 29% of normal-weight patients versus 40% each of overweight and obese patients reported headaches (P = .035). Overweight and obese patients' total cumulative doses (138.2 mg/kg and 140.6 mg/kg, respectively) were smaller than those of the normal-weight patients (143.7 mg/kg) (P < .001). Obese patients' length of treatment (6 months) was longer than that of the normal-weight (5 months) and overweight patients (5 months) (P = .031). Acne clearance, acne recurrence, and the time to recurrence after treatment discontinuation did not vary among the groups (P > .05). Relapse rates were 25% for normal-weight, 27% for overweight, and 35% for obese patients (P = .19).Table IEnrollment data, daily dose, and laboratory values stratified by BMI cohortNormal weight (N = 367)Overweight (N = 101)Obese (N = 82)P valueN (%) or median (interquartile range)Sex.29 Male261 (71)64 (63)55 (67) Female106 (29)37 (37)27 (33)Age (years) when first diagnosed13 (12-14)13 (12-14)13 (11.8-14)≤.001†Bold indicates statistical significance.Age (years) when first treated13 (12-15)13 (12-14)13 (12-14).001†Bold indicates statistical significance.Age (years) at the start of isotretinoin16 (15-17)16 (14.5-17)15 (14-16).004†Bold indicates statistical significance.Acne location∗Patient can have more than 1 location. Face367 (100)101 (100)82 (100)- Back321 (88)86 (85)76 (93).28 Chest259 (71)76 (75)70 (85).018†Bold indicates statistical significance.Month 1 daily dose (mg/kg)0.85 (0.65-0.97)0.77 (0.51-0.91)0.77 (0.59-0.87)≤.001†Bold indicates statistical significance.Month 2 daily dose (mg/kg)0.96 (0.87-1.04)0.90 (0.84-1.03)0.83 (0.71-0.94)≤.001†Bold indicates statistical significance.Pretreatment AST26 (22-33)27 (23-32)27 (23-33.3).53 ALT25 (20-31)27 (19.5-33.5)30 (23.8-39)≤.001†Bold indicates statistical significance. TRG82 (60-111.5)93 (67-130)96 (77-155)≤.001†Bold indicates statistical significance.On-treatment AST29 (24-35)29 (26-38.5)30 (24-37).24 ALT24 (19-30)27 (19-35)30 (24-38)≤.001†Bold indicates statistical significance. TRG109 (78.5-147)118 (94-154.5)136 (97-194.8)≤.001†Bold indicates statistical significance.ALT, Alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; TRG, triglyceride.∗ Patient can have more than 1 location.† Bold indicates statistical significance. Open table in a new tab Table IITreatment outcomes stratified by BMI cohortNormal weight (N = 367)Overweight (N = 101)Obese (N = 82)P valueN (%) or median (interquartile range)Acne clearance Face227 (62)61 (60)48 (59).84 Chest234 (90)67 (88)57 (81).16 Back265 (83)65 (76)57 (75).17Month of clearance Face4 (3-5)5 (4-6)5 (4-6).036†Bold indicates statistical significance. Chest3 (2-4)3 (2-4)3 (2-5).19 Back3 (2-4)3 (2-4)3 (2-5).20Change in management87 (24)32 (32)28 (35).06 Addition of topical steroids1 (<1)0 (0)0 (0).99 Addition of topical antibiotics3 (1)2 (2)1 (1).47 Addition of oral antibiotics1 (<1)1 (1)2 (2).07 Addition of oral steroids4 (1)3 (3)2 (2).22 Dose change81 (22)31 (31)24 (29).11 Other∗Other: azelaic acid cream, benzoyl peroxide, and topical retinoid.2 (1)2 (2)0 (0).26Complications Acne fulminans2 (1)2 (2)0 (0).26 Acne flaring53 (14)13 (13)10 (12).88 Depression/mood symptoms58 (16)20 (20)18 (22).30 Headaches106 (29)40 (40)33 (40).035†Bold indicates statistical significance. Double vision13 (4)6 (6)5 (6).35 Myalgias125 (34)43 (43)31 (38).27 Backache190 (52)56 (55)43 (52).82 Dry eyes171 (47)46 (46)34 (42).72 Cheilitis367 (100)101 (100)82 (100)- Nosebleeds218 (59)56 (55)49 (60).76 Xerosis349 (95)99 (98)81 (99).23 Other119 (32)42 (42)27 (33).23Cumulative dose (mg/kg)143.7 (124.0-160.4)138.2 (119.1-154.4)140.6 (117.9-156.1)≤.001†Bold indicates statistical significance.Length of treatment (months)5 (5-6)5 (4.5-6)6 (5-6).031†Bold indicates statistical significance.Acne relapse80 (25)21 (27)25 (35).19Time to relapse (months)5 (2.3-8)6 (3-9.5)4 (2-6.5).40BMI, Body mass index.∗ Other: azelaic acid cream, benzoyl peroxide, and topical retinoid.† Bold indicates statistical significance. Open table in a new tab Due to our large sample size, the small differences in daily and cumulative doses were statistically significant. However, they did not appear clinically meaningful, as clearance, remission, and side effects did not vary significantly. All median doses fell in the 0.5 to 1 mg/kg/day and 120 to 150 mg/kg standard dosing ranges, although alternative dosing strategies exist.1Zaenglein A.L. Pathy A.L. Schlosser B.J. et al.Guidelines of care for the management of acne vulgaris.J Am Acad Dermatol. 2016; 74: 945-973.e33https://doi.org/10.1016/j.jaad.2015.12.037Abstract Full Text Full Text PDF PubMed Scopus (700) Google Scholar,3Fallah H. Rademaker M. Isotretinoin in the management of acne vulgaris: practical prescribing.Int J Dermatol. 2021; 60: 451-460https://doi.org/10.1111/ijd.15089Crossref PubMed Scopus (8) Google Scholar Some studies support that acne clearance for at least 2 months before discontinuing isotretinoin is more meaningful than cumulative dose.3Fallah H. Rademaker M. Isotretinoin in the management of acne vulgaris: practical prescribing.Int J Dermatol. 2021; 60: 451-460https://doi.org/10.1111/ijd.15089Crossref PubMed Scopus (8) Google Scholar,4Rademaker M. Making sense of the effects of the cumulative dose of isotretinoin in acne vulgaris.Int J Dermatol. 2016; 55: 518-523https://doi.org/10.1111/ijd.12942Crossref PubMed Scopus (22) Google Scholar The reported relapse rates range from 20% to 60%, in line with the relapse rate we observed.5Blasiak R.C. Stamey C.R. Burkhart C.N. Lugo-Somolinos A. Morrell D.S. High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris.JAMA Dermatol. 2013; 149: 1392-1398https://doi.org/10.1001/jamadermatol.2013.6746Crossref PubMed Scopus (82) Google Scholar Our results suggest that current treatment strategies may be appropriate and safe for overweight and obese young people.The strength of our study is its large study population, whereas the weaknesses include incomplete follow-up and the limited number of providers. We may have missed relapses due to follow-up at outside facilities or inadequate time between treatment cessation and the start of data collection. However, given our extended study period and large referral center status, we expect to have captured most relapses. Future research should include a prospective study of different dosing strategies in overweight and obese young people. To the Editor: The response of obese and overweight young people to isotretinoin is understudied. This study compares isotretinoin treatment for acne in overweight and obese young people with their normal-weight peers to evaluate whether current dosing strategies (0.5-1 mg/kg/day for 120-150 mg/kg cumulative dose) are appropriate.1Zaenglein A.L. Pathy A.L. Schlosser B.J. et al.Guidelines of care for the management of acne vulgaris.J Am Acad Dermatol. 2016; 74: 945-973.e33https://doi.org/10.1016/j.jaad.2015.12.037Abstract Full Text Full Text PDF PubMed Scopus (700) Google Scholar We hypothesize that young people with a higher body mass index (BMI) may be effectively underdosed due to physicians' reluctance to prescribe higher daily doses of isotretinoin, potentially prolonging the treatment and impacting side effects. We hypothesize that there will be differences in daily dose (mg/kg), treatment length, and side effect incidence among the groups. A retrospective chart review was conducted on patients aged 10 to 24 years from 1 academic center who completed at least 2 months of isotretinoin therapy for acne from November 1, 2012, to October 31, 2019. The BMI was calculated for each patient. Centers for Disease Control growth charts were used to compute BMI percentiles and sort patients into BMI groups, as is the standard in pediatrics. Of the 550 patients eligible for analysis, 367 (67%) were normal weight or underweight, 101 (18%) were overweight, and 82 (14.9%) were obese (Table I). Overweight and obese patients had lower daily doses (mg/kg) than other participants during the first 2 months of treatment, although all fell in the 0.5 to 1.0 mg/kg/day range (P ≤ .001). Although alanine aminotransferase and triglyceride levels increased significantly as the BMI increased, only 1 instance of triglyceride elevation was clinically meaningful.2Barbieri J.S. Shin D.B. Wang S. Margolis D.J. Takeshita J. The clinical utility of laboratory monitoring during isotretinoin therapy for acne and changes to monitoring practices over time.J Am Acad Dermatol. 2020; 82: 72-79https://doi.org/10.1016/j.jaad.2019.06.025Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Table II summarizes the treatment outcomes. Headaches were the only complication that differed significantly: 29% of normal-weight patients versus 40% each of overweight and obese patients reported headaches (P = .035). Overweight and obese patients' total cumulative doses (138.2 mg/kg and 140.6 mg/kg, respectively) were smaller than those of the normal-weight patients (143.7 mg/kg) (P < .001). Obese patients' length of treatment (6 months) was longer than that of the normal-weight (5 months) and overweight patients (5 months) (P = .031). Acne clearance, acne recurrence, and the time to recurrence after treatment discontinuation did not vary among the groups (P > .05). Relapse rates were 25% for normal-weight, 27% for overweight, and 35% for obese patients (P = .19). ALT, Alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; TRG, triglyceride. BMI, Body mass index. Due to our large sample size, the small differences in daily and cumulative doses were statistically significant. However, they did not appear clinically meaningful, as clearance, remission, and side effects did not vary significantly. All median doses fell in the 0.5 to 1 mg/kg/day and 120 to 150 mg/kg standard dosing ranges, although alternative dosing strategies exist.1Zaenglein A.L. Pathy A.L. Schlosser B.J. et al.Guidelines of care for the management of acne vulgaris.J Am Acad Dermatol. 2016; 74: 945-973.e33https://doi.org/10.1016/j.jaad.2015.12.037Abstract Full Text Full Text PDF PubMed Scopus (700) Google Scholar,3Fallah H. Rademaker M. Isotretinoin in the management of acne vulgaris: practical prescribing.Int J Dermatol. 2021; 60: 451-460https://doi.org/10.1111/ijd.15089Crossref PubMed Scopus (8) Google Scholar Some studies support that acne clearance for at least 2 months before discontinuing isotretinoin is more meaningful than cumulative dose.3Fallah H. Rademaker M. Isotretinoin in the management of acne vulgaris: practical prescribing.Int J Dermatol. 2021; 60: 451-460https://doi.org/10.1111/ijd.15089Crossref PubMed Scopus (8) Google Scholar,4Rademaker M. Making sense of the effects of the cumulative dose of isotretinoin in acne vulgaris.Int J Dermatol. 2016; 55: 518-523https://doi.org/10.1111/ijd.12942Crossref PubMed Scopus (22) Google Scholar The reported relapse rates range from 20% to 60%, in line with the relapse rate we observed.5Blasiak R.C. Stamey C.R. Burkhart C.N. Lugo-Somolinos A. Morrell D.S. High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris.JAMA Dermatol. 2013; 149: 1392-1398https://doi.org/10.1001/jamadermatol.2013.6746Crossref PubMed Scopus (82) Google Scholar Our results suggest that current treatment strategies may be appropriate and safe for overweight and obese young people. The strength of our study is its large study population, whereas the weaknesses include incomplete follow-up and the limited number of providers. We may have missed relapses due to follow-up at outside facilities or inadequate time between treatment cessation and the start of data collection. However, given our extended study period and large referral center status, we expect to have captured most relapses. Future research should include a prospective study of different dosing strategies in overweight and obese young people. Dr Lalor receives royalties from UpToDate.com. Authors Tallmadge, Liegl, and Barbeau and Drs Pan, Patel, and Lalor have no conflicts of interest to disclose.