Treating atopic dermatitis: tacrolimus seems to be effective and safe

Atopic dermatitis (atopic eczema) is a common skin condition that can have a big impact on the quality of life of both children and adults. I’ve been there, managing it for myself and for my children. We’ve been through wet wraps, preparations to put in the bath and to wash with; we’ve read about animals called Itchy and Scratchy who are supposed to make my child feel better about it all; and of course we’ve been through an awful lot of different creams. There are always two pressing questions, once you get onto medicated stuff, usually steroid creams – does it work and is it safe? Possible side effects, such as skin thinning, are quick to be mentioned.

Is there any evidence to back concerns about the safetyRefers to serious adverse effects, such as those that threaten life, require or prolong hospitalization, result in permanent disability, or cause birth defects. of tacrolimus?

A possible alternative to the topical corticosteroids (TCS) which form the mainstay of treating atopic dermatitis is tacrolimus ointment which, along with pimecrolimus, is from a class of drugs called topical calcineurin inhibitors. It comes in two strengths, 0.1% and 0.03%. Newer than corticosteroids, it is important to know about its effectivenessThe ability of an intervention (for example a drug, surgery, or exercise) to produce a desired effect, such as reduce symptoms. and safety. Concerns have been raised about an increased riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of cancers such as skin cancer and lymphomas, based on the possible risk of absorption into the blood stream, but this is controversial, with no strong supporting evidence.

A Cochrane review has now been updated with the latest evidence from 20 randomizedRandomization is the process of randomly dividing into groups the people taking part in a trial. One group (the intervention group) will be given the intervention being tested (for example a drug, surgery, or exercise) and compared with a group which does not receive the intervention (the control group).   controlled trialsA trial in which a group (the ‘intervention group’) is given a intervention being tested (for example a drug, surgery, or exercise) is compared with a group which does not receive the intervention (the ‘control group’). with almost 6000 children and adults with moderate to severe atopic dermatitis, comparing topical tacrolimus with other active treatments. Previous research has shown that tacrolimus is better than placeboAn intervention that appears to be the same as that which is being assessed but does not have the active component. For example, a placebo could be a tablet made of sugar, compared with a tablet containing a medicine. (a similar preparation without any drug). To find out as much as possible about side effects, the reviewers not only looked at dataData is the information collected through research. in the trialsClinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. but also looked for other types of research, safety letters and industry warnings.

Here’s what they found:

• Tacrolimus 0.1% was better than low-potency TCS on the face and neck and moderate-potency TCS on the trunk and extremities
• Tacrolimus 0.03% more than doubled the chance of improvement compared with mild TCS or pimecrolimus 1%. In most trials, there was no difference between tacrolimus 0.03% and moderate strength TCS but in two studies TCS were slightly better
• Side effects:
  • Burning and itching were more common with tacrolimus than TCS but symptoms were mild and short-lived
  • There was no difference in skin infection
  • Local (happening where applied) side effects were more common with tacrolimus than pimecrolimus and lasted longer: between 30 minutes and 12 hours compared with less than 30 minutes.
  • Serious side effects were rare in all groups and not thought to be related to treatmentSomething done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes.
  • It was rare to find the drug entering the bloodstream and only in diseases with severe skin barrier problems
  • No evidence was found to support the possible increased risk of skin thinning or cancer

How reliable is the evidence?

The evidence was of variableA factor that differs among and between groups of people. Examples include people’s age, sex, depression score or smoking habits.   quality. The drugs, doses and outcomesOutcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise). In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’. varied between studies so it was not always possible to combine the results, which is done whenever possible in a systematic review. There’s good evidence that tacrolimus 0.1% is better than the milder 0.03% preparation and mild TCS. The evidence is less reliable when comparing both strengths of tacrolimus with moderate to potent TCS.

The research reported objective measures of improvement and doctor’s assessments of improvement but few reported patient’s self-assessments; shame!

The bottom line?

The reviewers say: “Tacrolimus ointment seems to be safe and effective for the treatment of moderate to severe atopic dermatitis in both children and adults.”

Looking ahead to more research on safety

Research was started in 2005 to assess the risk of cancers in children associated with topical tacrolimus ointment use, following a large cohort of children over ten years. The APPLES project will contribute valuable data on the long term safety of topical tacrolimus.

Links:

Cury Martins J, Martins C, Aoki V, Gois AFT, Ishii HA, da Silva EMK. Topical tacrolimus for atopic dermatitis. Cochrane Database of Systematic ReviewsIn systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. 2015, Issue 7. Art. No.: CD009864. DOI: 10.1002/14651858.CD009864.pub2.

Plain language summary of this review: http://www.cochrane.org/CD009864/SKIN_topical-tacrolimus-for-atopic-dermatitis