Hidradenitis suppurativa and pulmonary diseases, the efficacy of tofacitinib in severe alopecia areata, new sequencing technology to screen for genetic diseases
Dr Christian Derancourt
The hidden cost of systemic treatments (poster 3651): the goal of this cost analysis carried out in North Carolina was to compare the administrative and follow-up costs over one year (medications, consultation, and biological analyses, assuming no anomalies) for the main traditional systemic treatments used in dermatology, according to the American recommendations and reimbursement data in force in 2016. The results were very much in favour of methotrexate (€576) then acitretin (€592), azathioprine (€845), mycophenolate mofetil (€1231) and finally cyclosporine (€1641). The high costs of cyclosporine and mycophenolate mofetil are partly explained by the need for monthly follow-up, unlike the other treatments. This global approach, which is not limited to the cost of the product, is interesting and is worth developing, to help in public decision making. However, let's not forget that for the patient and therefore the practitioner's prescription, it is consideration of the risk/benefit ratio that is most important, within, of course, the recommendations on the cost/effectiveness ratio.
For the first time, a study has analysed the link between hidradenitis suppurativa and lung diseases with a view to determining the comorbidities of this inflammatory disease. The study, carried out in Israel, was particularly impressive due to the number of subjects involved: 3207 carriers of hidradenitis suppurativa and 6412 controls. The methodology of choice for the carriers and the controls was not, however, clearly specified in this national study based on data. The study found a link with asthma (OR=1.3; CI95% 1.1-1.6]) and chronic obstructive pulmonary disease (OR=1.1; CI95% 1.0-1.8]). It is worth confirming the reality of this link as it could have a clinical benefit for the practitioner.
Dr Rémi Maghia
Oral tofacitinib in severe alopecia areata
The tremendous success of small molecules in treating psoriasis leads us to wonder if, in the long term, this approach could be used in the very difficult treatment of alopecia areata.
Tofacitinib is an oral 1/3 JAK inhibitor, being developed for psoriasis and rheumatoid polyarthritis.
Justin Ko, from the Stanford University School of Medicine, presented a study assessing the efficacy and tolerance of this JAK inhibitor in patients suffering from severe alopecia areata.
There was the observation* ("Killing two birds with one stone") for which Ko showed photos, of a patient treated with tofacitinib citrate for psoriasis on the body and scalp, but also suffering from alopecia universalis. Remarkably, the patient's psoriasis cleared up and the alopecia regrew completely in less than 6 months.
According to Ko, the initial hypothesis was to target the JAK-STAT signalling pathway within the NK T cells and the follicle cells, with a view to obtaining a reversal of the alopecia process with hair regrowth. It is indeed thought that the JAK-STAT signalling pathway plays a key role in the pathogenesis of alopecia.
Open, single-arm study: the patients took 5-mg tofacitinib tablets twice a day for three months. The primary objective was hair regrowth, assessed by the SALT (Severity of Alopecia Tool) score. 66 patients completed the study, presenting various types of alopecia: universalis (71%), in patches (17%), total (7.5%), and ophiasis (4.5%). Note: peribulbar inflammation was significant in 82% of cases, and minimal in 18% of cases. The results after 3 months: significant median change of 21% in the SALT score. Broadly speaking, three groups, equal in size: group 1: change in score of 0% to 5%, group 2: change in score of 6% to 50%, group 3: change in score of 50% to 100%. The best clinical response was correlated with peribulbar inflammation upon biopsy of the scalp. A lengthy evolution in the disease was correlated with a less remarkable therapeutic response. The response to treatment after 3 months of tofacitinib was not maintained, with an average relapse time of 8.5 months. Side effects: minor grade I and II infections; higher hepatic constants in NASH patients, reversible when the medication is discontinued; no leukopenia, anaemia, rise in lipids; no rise in cancers.
In conclusion: the authors suggest that oral tofacitinib is an effective treatment which is not dangerous but simply suspends the advanced and recalcitrant forms of alopecia areata. The limitations of the study are its small scale, the absence of double blind and the bias of the advanced or recalcitrant forms.
What does the future hold for this treatment, what will the maintenance methods be? That remains to be seen.
It is certain that we can't remain indifferent to the photos of Ko's patient, a patient whose life was turned upside down by the total loss of her hair, but who experienced complete regrowth after treatment.
Several studies are ongoing in the United States.
* Craiglow J Invest Dermatol 2014,134: 2988-90
Prof Frédéric Caux
Bullous pemphigoid is rarely of medicinal origin. Many years ago, it was suspected that this bullous dermatosis was induced by spironolactone, as shown in an epidemiological study. More recently, a new generation of oral antidiabetics, dipeptidyl peptidase-4 inhibitors, also called gliptins, were linked to the appearance of bullous pemphigoid. A poster (P3493) showed a Spanish series of 5 cases of bullous pemphigoid induced by gliptins collected from 3 specialised hospital departments over 3 years. The patients were 3 women and 2 men with an average age of 76. On average, gliptin was started 8 months before the bullous pemphigoid appeared. Vildagliptin was involved in 4 cases, and sitagliptin in 1. From a clinical and biological point of view, the only peculiarity was the absence of hypereosinophilia. After stopping gliptin, 2 patients were treated with local corticosteroids and 3 with a systemic treatment with rapid remission and discontinuation of treatment in 6 months. In the literature, 17 cases were described as clinical or short-series cases, and a pharmacovigilance study reported on 41 cases. Dermatologists must therefore know to suspect a medicinal original when bullous pemphigoid occurs in a diabetic patient taking gliptin, and must consider stopping the treatment.
During the plenary session, Amy Paller, a paediatric dermatology specialist in Chicago, showed the power of the new sequencing technologies for diagnosing genetic diseases. Exome sequencing (WES) is a technique in which all the coding regions of the genome are analysed. This method means that only 1% of the genome needs to be sequenced to identify about 90% of the mutations. Whole genome sequencing (WGS) makes it possible to identify all the mutations, in particular the duplications and translocations present in the intronic and promoter regions which are not detected in WES. WGS also makes it possible to carry out phenotype-genotype correlations based on the analysis of multiple genes. The price of these two techniques has dropped significantly ($1000) and is much lower than that for traditional Sanger sequencing ($12,000) which must be accessible in clinics. The techniques are used to identify mutations in new genes, describe new diseases or decipher complex clinical tables (mosaicism). However, the analysis of all the genes can sometimes lead to difficulties such as the unexpected discovery of non-paternity or susceptibility to other diseases (a predisposition to cancer, or to a neurodegenerative disease). However, these new technologies will lead to a major breakthrough in treating patients by making it easier to reach an accurate diagnosis and therefore ensure that the right treatment is chosen within the framework of personalised medicine.