Oral isotretinoin confirmed as most effective treatment for acne in network meta-analysis

27th July 2023

A network meta-analysis of 221 randomised controlled trials with over 65,000 patients, has confirmed that oral isotretinoin is the most effective acne treatment.

Acne is extremely common, affecting virtually everyone between the ages of 15 and 17 years to some extent, but is moderate to severe in up to 20% of cases. Acne can be managed with broad range of topical and oral agents including antibiotics and even aldosterone receptor antagonists such as spironolactone.

Now, in the largest network meta-analysis into pharmacological interventions in acne vulgaris to date, published in the Annals of Family Medicine, researchers from Taiwan and the US concluded that oral isotretinoin is the most effective treatment.

The team sought to provide broad and detailed comparative efficacy data for a range of pharmacological interventions in acne to reduce both inflammatory and noninflammatory lesions. The primary outcome of interest was the mean percentage reduction in total, inflammatory, and noninflammatory lesions, and the mean absolute reduction in lesion counts were secondary outcomes.

Oral isotretinoin and reduction in lesion count

The analysis included a total of 210 articles describing 221 trials, which enrolled a total of 65,601 patients. Across all of the trials, the mean age of patients was 20 years and the median duration of treatment was 12 weeks. In addition, the median baseline lesion counts were 71.5 for the total lesions, 27 for inflammatory lesions and 44 for noninflammatory lesions.

The comprehensive analysis compared 37 treatment nodes, which included six oral antibiotics, five topical antibiotics, oral isotretinoin, five topical retinoids, six combined oral contraceptives, topical clascoterone, 10 combination therapies, benzoyl peroxide (BPO), azelaic acid and placebo.

The most effective treatment, compared to placebo, was oral isotretinoin (mean difference, MD = 48.41, p = 1.0). The second most effective option was triple therapy containing a topical antibiotic, a topical retinoid and BPO (MD = 38.15, p = 0.95). This was followed closely by triple therapy with an oral antibiotic, a topical retinoid and BPO (MD = 34.83, p = 0.90).

The researchers also found a similar ranking of treatment efficacy in the analysis of absolute reduction in total lesion count.

When examining mono-therapies, both oral and topical antibiotics had comparable efficacy to topical retinoids for inflammatory lesions. In contrast, oral or topical antibiotic therapy was far less effective for noninflammatory lesions and the researchers advised against monotherapy due to the risk of developing bacterial resistance.

Another comparison revealed how the combination of a topical retinoid and BPO was as effective as a combination of an oral antibiotic with a topical retinoid at reducing inflammatory lesion counts.

Survival benefit from carboplatin in children with high risk medulloblastoma

3rd August 2021

The use of carboplatin but not isotretinoin in children with high-risk medulloblastoma led to an increase in event-free survival at 5 years.

Medulloblastoma is the second most common, malignant brain tumour in children. It develops in between 250 and 400 children each year and more than 70% of cases occur in those younger than 10 years of age. It is a highly invasive cancer that arises in the cerebellum and disseminates throughout the central nervous system. Survival depends to a large extent on whether or not the disease has spread. For example, among children without disseminated disease, the event-free survival at 5 years has been shown to be around 80%. However, the cancer can return and the 3-year survival rate for relapsed cancer is low at around 18%. Medulloblastomas are categorised into different groups, with group 3 being more aggressive and therefore high-risk, with a 5-year survival of approximately 20%–30%. The use of carboplatin as a radiosensitiser has been found to be a promising strategy in patients with high-risk medulloblastoma and isotretinoin has been shown to induce apoptosis of medulloblastoma cells. There is also data showing that the addition of isotretinoin to carboplatin, enhances tumour sensitivity in squamous cell carcinoma xenografts.

With some evidence suggesting that the combination of isotretinoin and carboplatin may be of greater value in the treatment of medulloblastoma, a team from the Cancer and Blood Disorders Centre, Seattle, US, decided to undertake a randomised trial to examine the impact on survival of combination therapy in children with high-risk (group 3) medulloblastoma. Included patients were randomised to chemotherapy with 36-GY craniospinal radiation therapy and weekly vincristine with or without daily carboplatin, followed by 6 cycles of maintenance chemotherapy with or without 12 cycles of isotretinoin. The primary outcome of the trial was event-free survival.

Findings
There were 261 children with a mean age of 8.6 years (70% male), 72% of whom at metastatic disease included in the analysis and the median follow-up time was 6.7 years. For all participants, the 5-year overall survival was 73.4% (95% CI 66.7–80.1%). The overall 5-year event-free survival with carboplatin was 66.4% (95% CI 56.4%–76.4%) vs 59.2% (95% CI 48.8%–69.6%) without carboplatin. However, in the subgroup of patients with group 3 medulloblastoma, the 5-year event-free survival for patients given carboplatin was even higher, 73.2% vs 53.7% without carboplatin. In addition, the overall survival with carboplatin was 82.8% vs 63.7% without the drug. The isotretinoin arm was closed early due to an interim analysis finding that addition of the drug was unlikely to have a positive effect on event-free survival, i.e., 68.6% with isotretinoin vs 67.8% without.
The authors concluded that the use of carboplatin and radiotherapy should be recommended for paediatric patients with high risk medulloblastoma although use of isotretinoin added little value.

Citation
Leary SES et al. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma. A Randomised Clinical Trial from the Children’s Oncology Group. JAMA Oncol 2021