Questions remain for breakthrough drug that can clear severe eczema

    5 October 2016

    A drug can clear severe eczema in four out of 10 patients, according to a report in the New England Journal of Medicine.

    During the 16-week trial on 1,400 atopic dermatitis patients, the drug (which has to be injected every two weeks) was found to alleviate symptoms within 14 days. Symptoms disappeared entirely in almost 40 per cent of trial participants.

    Side effects included a slightly increased risk of conjunctivitis and swelling at the injection site.

    The drug works by blocking two specific molecules of the immune system that are overproduced in patients with atopic dermatitis.

    Dr George Yancopoulos, the chief scientific officer at Regeneron, the company that makes the drug, says he expects the US Food and Drug Administration to make a decision on licensing it by March.

    Instant analysis
    Atopic dermatitis, a severe form of eczema, is a significantly debilitating condition, causing itching, sores, broken skin and skin infections.

    Treatments are often poor and tend to be used in reaction to symptoms rather than preventing them in the first place. There is a heavy reliance on drugs that suppress the immune system, for example systemic or topical steroids or immunomodulators.

    This study looked at the impact of dupilumab, a monoclonal antibody, in two randomised, double-blind, parallel trials in North America, Europe and Asia. The antibody was injected weekly (or fortnightly for one group) for 16 weeks.

    The antibody targets two main inflammatory mediators, or cytokines, which drive the condition forward: interleukin-4 and interleukin-13.

    In early trials it was shown to be effective in allergic conditions.

    The end point was an IGA (dermatitis score) of 0 or 1 showing the eczema was almost or completely cleared, or a reduction from baseline of at least two points at week 16.

    The secondary end point was an improvement of at least 75 per cent of eczema on the EASI-75 scoring system. Other secondary end points of improvement were also identified, including quality of life and anxiety and depression scoring.

    Two batches of patients were randomised – 671 in SOLO 1 and 708 in SOLO 2. In SOLO 1 the eczema was almost or completely cleared in 85 patients (38 per cent) receiving dupilumab on alternate weeks and in 87 receiving weekly dupilumab, compared with 23 receiving placebo.

    This result was comparable in SOLO 2 with 84 patients (36 per cent) showing the result on alternate weeks and 87 patients (36 per cent) receiving weekly dupilumab, compared with only 20 placebo patients.

    For the secondary end points of improvement, a similar marked improvement compared to placebo was seen, with rates around 70 per cent change from baseline compared to 37 per cent with placebo in SOLO 1 and 30 per cent in SOLO 2, as were quality of life scoring and depression and anxiety scores. Adverse events in each of the groups were similar and of low number.

    The study notes that there were two deaths in the dupilumab groups in the study, the first in an asthmatic who had an attack around 84 days after the last dose of the drug, the second a suicide in a man with a history of depressive disorder requiring hospitalisation. One of the reasons the study looked at anxiety and depression was that this condition significantly affects patients’ mood and wellbeing to the point where, perhaps for some people, this study represented a final throw of the dice. Suicidal thoughts in this condition are common. According to the New York Times, one sufferer spent close to $100,000 to be included in the trial.

    Herpes viral infections were seen to be more prevalent in the dupilumab groups, as were nasopharyngitis and conjunctivitis, for which an explanation is still sought. Skin infections were more prevalent in placebo groups.

    The study showed that dupilumab was better than placebo in treating atopic dermatitis and may be an effective treatment for some patients with this significantly debilitating condition. However, longer duration and larger studies are required to investigate safety concerns and gain further information on adverse events.

    My reservation, though, is that a ‘treatment versus nothing’ trial is rather unhelpful. It is unethical to demonstrate superiority over a placebo when really you ought to show it works better than the current best treatment. Pharmaceutical companies created outrage when they did this in Africa with treatments for meningitis. The incredibly sad case of suicide should be looked into – the danger is that trial participants can be given false hope and end up thinking that their problem can be fixed.

    I would like a comparison between dupilumab and commonly used treatments for the condition and am keen to see how this develops.
    Research score: 3/5