Introduction

Oral isotretinoin is considered as the mainstay of treatment for acne due to its efficacy, ability to target all the four pathophysiologic factors, high rates of permanent remission, and prevention of permanent scarring in acne. There are few comparative studies on low‑dose regimens of oral isotretinoin in the Indian literature.

Aim

To assess and compare the efficacy and tolerability of two low-dose oral isotretinoin treatment regimens (20 mg daily and 20 mg alternate days) in Indian patients with moderate to severe acne vulgaris.

Patient Profile

Patients with moderate to severe acne vulgaris

• Patients were graded into mild, moderate, and severe acne based on criteria described by Pochi.

  Table 1: Pochi et al. criteria for grading of acne vulgaris

  Severity	Papules/pustules	Nodules
  Mild	Few to several	None
  Moderate	Several to many	Few to several
  Severe	Numerous and/or extensive	Many

  Number of lesions <5 = few, 5-15 = many and >15 lesions = several

  Methods

• Prospective randomized comparative study
• 234 patients were randomized into two groups
  • Group A: Daily; n=118
  • Group B: Alternate days; n=116

  Study Treatment

• Groups A and B were treated with a fixed dose of 20 mg of oral isotretinoin daily and alternate days, respectively, for a total period of 24 weeks and followed up for 12 weeks post-therapy.
• Patients were instructed to apply topical 1% clindamycin gel twice daily and white petroleum jelly on lips when required.

  Assessment parameters

• Treatment response was analysed on the basis of mean percentage decrease in total acne load (TAL), response criteria, and disease severity.
• Patients were evaluated at an interval of two weeks for 24 weeks then six weekly interval for 12 weeks after completion of treatment.

• Total acne load (TAL) was calculated with the help of Definition Severity index

Table 2: Definition severity index

Total acne load = [(number of severity index 0.5 lesions) × 0.5] + [(number of severity index 1 lesions) × 1] + [(number of severity index 2 lesions) × 2] + [(number of severity index 3 lesions) × 3]

• Response criteria was define as follows:

• 1+ = Poor response (<30% reduction in the lesion counts)
• 2+ = Fair response (30%–60% reduction in the lesion counts)
• 3+ = Good response (60%–90% reduction in the lesion counts)
• 4+ = Excellent response (>90% reduction in the lesion counts).

• Complete blood cell counts, liver function tests, and serum lipid profile were done initially & repeated at four and eight weeks thereafter.
• Adverse effects were recorded at each visit

Results

• Treatment response based on mean percentage decrease in TAL

• A statistically significant decrease in TAL was observed in both groups (P < 0.001 at each follow up)
• Mean percentage decrease in TAL was significantly better in group A as compared with Group B during the entire study period (P < 0.01 at each follow up). (Table 1)
• The mean percentage decrease in TAL in Group A and Group B at 24 weeks was 98.99% and 97.69%, respectively ((P < 0.01), which decreased to 96.03% and 92.82%, respectively, at 36 weeks ((P < 0.01).

Table 1: Mean percentage decrease in TAL at different time intervals in both groups

• Treatment response based on severity of acne
  • In the severe acne, Group A performed significantly better than Group B at the end of 36 weeks (P < 0.005)
  • While in the moderate acne, significant difference in the response between both groups was observed only up to 12 weeks (P value < 0.02)
• Treatment response based on response criteria
  • At the end of 24 weeks, the excellent response in treatment groups A and B was seen in 98.3% and 93.96% patients, respectively (P=0.166), which at the end of 36 weeks decreased to 90.6% and 74.1% patients, respectively (P=0.004)

  Figure 1: Mean percentage decrease in TAL in Group A and Group B at 24 weeks

  

  P

• At 24 weeks, 68.64% (Group A) and 56.03% (Group B) patients were acne free, which decreased to 50.84% and 39.65%, respectively (P= 0.51) at the end of 36 weeks. However, the patients developing acne recurrence had mild‑grade acne.
• No serious side effects were observed.
  • Most common adverse effects observed were cheilitis (Group A, 97.46% and Group B, 95.69%), and dry skin (Group A, ‑ 16.9% and Group B, 10.3%).
  • Pruritus, dry eyes, hair fall, urticaria, dry mouth, dry nose, facial redness on sun exposure, menstrual irregularities, headache, myalgia, arthralgia, oral aphthous, moderately increased triglycerides level, abnormal liver function test, forgetfulness, dermographism, and pigmentation of face were less frequent adverse events
  • Group A showed higher frequency of adverse events as compared with Group B but, the difference was not statistically significant (P > 0.05)
  • All the adverse effects were managed successfully; none of the patients required discontinuation of therapy because of adverse effects.

Conclusion

• Both daily and alternate isotretinoin regimens were well tolerated and were an effective treatment for moderate to severe acne vulgaris.
• For moderate acne 20 mg alternate day regimen may be preferred
• A 20 mg daily regimen was a better choice for severe acne in terms of response.

Reference

Indian Dermatol Online J 2016;7:378-85.