Acne vulgaris is chronic inflammatory disease affecting the skin, and one of the most common dermatological conditions worldwide. In addition to the bacterial component of acne, a combination of disrupted sebaceous gland activity, dysregulated hormone microenvironment and immune cell dysfunction are thought to drive the condition.
Since the 1970s, minocycline, a semi-synthetic drug derived from tetracycline, has been used to treat a range of infections, including acne. Nowadays, it is considered for the treatment of moderate-to-severe disease, where it appears to be effective at killing Propionibacterium acnes, the bacterial species that thrives in the hair follicle environment and which contributes to acne development. In addition to minocycline’s bacteriostatic properties, this drug also has other effects which likely contribute to its efficacy in treating acne. These include anti-inflammatory effects such as modulating cytokines in the skin and inhibiting T-cell activation and proliferation, in addition to inhibitory effects on matrix metalloproteinases (MMPs) which can play a role in skin remodelling and hyper-proliferation.
Weighing benefit vs risk
When considering its use in acne, balancing the benefits of minocycline with the risk of rare yet potentially serious systemic adverse effects associated with the drug is important.
On one hand, minocycline has a better pharmacokinetic profile compared to first-generation tetracyclines, with excellent absorption (not impaired by milk or food) and tissue penetration, and a half-life that allows for once-daily dosing. Its efficacy in treating acne seems to be as good if not better than other tetracycline options (limited data exists by way of head-to-head comparisons in controlled trials), and a recent comparison of tetracycline, doxycycline and minocycline in 22 clinical isolates of P. acnes showed minocycline to have the lowest minimum inhibitory concentration (MIC) of the three drugs, in all cases (Kim et al 2016).
On the other hand, short-term use of minocycline is historically associated with adverse effects such as hyper-pigmentation, CNS-effects such as vertigo and dizziness, and hypersensitivity affecting the liver, lungs and kidney. Long-term use can cause the development of auto-immune hepatitis or systemic lupus erythematosus.
Formulating towards improved outcomes
Since 2006, an extended-release (ER) version of minocycline has been available (currently versions such as Minocin SA (Meda AB) and Minosil (Pinewood Healthcare) are available in Ireland). ER-minocycline formulations aim to lower the maximum concentration of drug in the blood (and the drug concentration crossing the blood-brain barrier) in an attempt to reduce the adverse effects profile. Available data suggests that ER-minocycline carries the same risk of vestibular adverse effects as placebo (i.e. low risk of these events occurring) (Torok HM, 2013), but randomised, controlled comparisons of adverse effects profiles between ER-minocycline and immediate-release (IR) minocycline have proved difficult to find. A topical minocycline foam (FMX-101 by Foamix Pharmaceuticals Ltd) is currently under development which aims to further reduce systemic exposure to minocycline.
Combating antibiotic resistance in acne
With antibiotic resistance in P. acnes becoming a widespread issue globally, a recent systematic review recommends that oral antibiotics should not be used as a monotherapy in acne (instead combine with a topical retinoid) and should be limited to short periods where possible, in order to limit the spread of resistance (Walsh et al 2016). Another review studied the prescribing behaviour for oral antibiotics in the treatment of acne among GPs in the UK and found that antibiotic use is not aligned with current guideline recommendations. For example, 29 per cent of courses of oral tetracyclines prescribed by GPs in the UK exceeded 6 months, and 62 per cent did not include topical retinoids (Barbieri et al 2016).
Combating antibiotic resistance in acne relies on responsible prescription of oral antibiotics, whilst careful monitoring of patients on minocycline can help mitigate against potential side-effects and maximise the clinical utility of this antibiotic in the treatment of acne.