David Rosmarin

Cyclosporine and psoriasis: 2008 National Psoriasis Foundation∗ Consensus Conference

BACKGROUND Cyclosporine is a valuable option for the treatment of psoriasis. This report summarizes studies regarding the use of cyclosporine since the last guidelines were published in 1998. OBJECTIVE A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options. Our aim was to achieve a consensus on new updated guidelines for the use of cyclosporine in the treatment of psoriasis. METHODS Reports in the literature were reviewed regarding cyclosporine therapy. LIMITATIONS There are few evidence-based studies on the treatment of psoriasis with cyclosporine. RESULTS A consensus was achieved on the use of cyclosporine in psoriasis including specific recommendations on dosing, monitoring, and use of cyclosporine in special situations. The consensus received approval from members of the National Psoriasis Foundation Medical Board. CONCLUSIONS Cyclosporine is a safe and effective drug for the treatment of psoriasis. It has a particularly useful role in managing psoriatic crises, treating psoriasis unresponsive to other modalities, bridging to other therapies, and treating psoriasis within a rotational scheme of other medications. Appropriate patient selection and monitoring will significantly decrease the risks of side effects.

Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib

Background Existing therapies for vitiligo are limited in efficacy and can be associated with undesirable side effects. Topical Janus kinase inhibitors may offer a new therapeutic option for vitiligo. Objective We sought to assess the role of topical ruxolitinib 1.5% cream, a Janus kinase inhibitor, in vitiligo treatment. Methods This 20‐week, open‐label, proof‐of‐concept trial of twice‐daily topical ruxolitinib 1.5% cream was conducted in 12 patients with a minimum of 1% affected body surface area of vitiligo. The primary outcome was percent improvement in Vitiligo Area Scoring Index from baseline to week 20. Results Of 12 patients screened, 11 were enrolled and 9 completed the study (54.5% men; mean age, 52 years). Four patients with significant facial involvement at baseline had a 76% improvement in facial Vitiligo Area Scoring Index scores at week 20 (95% confidence interval, 53‐99%; P = .001). A 23% improvement in overall Vitiligo Area Scoring Index scores was observed in all enrolled patients at week 20 (95% confidence interval, 4‐43%; P = .02). Three of 8 patients responded on body surfaces and 1 of 8 patients responded on acral surfaces. Adverse events were minor, including erythema, hyperpigmentation, and transient acne. Limitations Limitations of the study include the small sample size and open‐label study design. Conclusions Topical ruxolitinib 1.5% cream provided significant repigmentation in facial vitiligo and may offer a valuable new treatment for vitiligo.

Patch testing a patient with allergic contact hand dermatitis who is taking infliximab

We report the case of a patient who developed allergic contact hand dermatitis while receiving infliximab infusions for psoriasis and psoriatic arthritis. Patch testing showed multiple positive allergens. To our knowledge, this is the first case report of successful patch testing in a patient receiving tumor necrosis factor-alpha (TNF-alpha) blockade therapy. TNF-alpha blockers do not necessarily suppress allergic contact hypersensitivity and are not an absolute contraindication to patch testing.

Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study

BACKGROUND Guselkumab, a human monoclonal antibody that binds to the p19 subunit of interleukin 23, has been approved for the treatment of moderate-to-severe psoriasis. Psoriatic arthritis is a common comorbidity of psoriasis with an umet need for novel treatments. We assessed the efficacy and safety of guselkumab in patients with active psoriatic arthritis. METHODS We did a randomised, double-blind, placebo-controlled, phase 2a trial at 34 rheumatology and dermatology practices in Canada, Germany, Poland, Romania, Russia, Spain, and the USA. Eligible participants were aged 18 years or older with active psoriatic arthritis and plaque psoriasis affecting at least 3% of their body surface area, with three or more of 66 tender joints and three or more of 68 swollen joints, who had an inadequate response or intolerance to standard treatments. We randomly assigned patients (2:1) via a central interactive web-response system using computer-generated permuted blocks with a block size of six, stratified by previous anti-tumour necrosis factor-α use, to receive subcutaneous guselkumab 100 mg or placebo at week 0, week 4, and every 8 weeks thereafter for 24 weeks. Patients, investigators, and site staff were masked to treatment assignment until final database lock at week 56. At week 16, patients with less than 5% improvement in swollen and tender joint counts were eligible for early escape to ustekinumab. At week 24, the remaining placebo-treated patients crossed over to receive guselkumab 100 mg at weeks 24, 28, 36, and 44 and guselkumab-treated patients received a placebo injection at week 24, followed by guselkumab injections at weeks 28, 36, and 44. The primary endpoint was the proportion of patients with at least 20% improvement at week 24 in signs and symptoms of psoriatic arthritis according to American College of Rheumatology criteria (ACR20) in the modified intention-to-treat population (ie, all randomly assigned patients who received at least one dose of study treatment). Safety analyses included patients according to the study drug received. This study is registered with ClinicalTrials.gov, number NCT02319759. FINDINGS Between March 27, 2015, and Jan 17, 2017, we randomly assigned 149 patients to treatment: 100 to guselkumab and 49 to placebo. 17 (35%) of 49 patients in the placebo group and ten (10%) of 100 patients in the guselkumab group were eligible for early escape to ustekinumab at week 16. 29 (59%) of 49 patients in the placebo group crossed over and received guselkumab at week 24. Three (6%) of 49 patients in the placebo group, one (3%) of 29 patients who crossed over from placebo to guselkumab, and six (6%) of 100 patients in the guselkumab group discontinued study treatment before week 44. 58 (58%) of 100 patients in the guselkumab group and nine (18%) of 49 patients in the placebo group achieved an ACR20 response at week 24 (percentage difference 39·7% [95% CI 25·3-54·1]; p<0·0001). Between week 0 and week 24, 36 (36%) of 100 guselkumab-treated patients and 16 (33%) of 49 placebo-treated patients had at least one adverse event. The most frequent adverse event was infection in both groups (16 [16%] of 100 patients in the guselkumab group vs ten [20%] of 49 patients in the placebo group). The prevalence of adverse events between week 0 and week 56 in guselkumab-treated patients (51 [40%] of 129) indicated no disproportional increase with longer guselkumab exposure. No deaths occurred. INTERPRETATION Guselkumab, a novel anti-interleukin 23p19 antibody, significantly improved signs and symptoms of active psoriatic arthritis and was well tolerated during 44 weeks of treatment. The results of this study support further development of guselkumab as a novel and comprehensive treatment in psoriatic arthritis. FUNDING Janssen Research & Development.

Importance of light in the treatment of vitiligo with JAK-inhibitors

Dear Editor,Vitiligo is an autoimmune pigmentary disorder characterized by depigmented patches of skin with a selective loss of melanocytes. Given the absence or diminished numbers of melanocytes i...

Anti IL‐17 flared psoriasis in a patient on secukinumab

Dear Editor, Psoriasis is a chronic, autoimmune inflammatory disease in which cytokines tumor necrosis factor a (TNF), interleukin (IL) 23, and interleukin 17 play a pivotal role in the pathogenesis (Nestle, Kaplan, & Barker, 2009). Paradoxical or de novo psoriasis developing in patients undergoing anti-TNF therapy has been well documented in the literature (de Gannes et al., 2007). We describe a patient who developed inverse and palmoplantar psoriasis on the IL-17 antagonist secukinumab.

JAK-STAT signaling pathway inhibition: a role for treatment of various dermatologic diseases

Cutaneous inflammatory conditions such as psoriasis, atopic dermatitis, alopecia areata, vitiligo, and connective tissue diseases often remain a challenge to treat. Although there is an in-depth understanding of the clinical presentation of these diseases, much less is known regarding the pathophysiology. This has limited the effective treatment options for patients. A more detailed understanding of the pathogenesis of each disease will lead to newer targeted medications with less morbidity. Though there are different pathways involved in these diseases, the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription proteins (STAT) signaling pathway is common to them all. Therefore, this review article endeavors to substantiate the immunopathology and clinical utility of the JAK inhibitors as treatments for different chronic inflammatory diseases of the skin.Hidradenitis suppurativa (HS) is a frequently devastating inflammatory skin disorder. Although many treatments have been tried and tested to date, there is only one Food and Drug Administration-approved treatment option, adalimumab, which is currently indicated for moderateto- severe HS. Our understanding of the management of HS with biologic agents and with nonantibiotic and/ or antimicrobial systemic therapies continues to evolve. In this article, we summarize the existing data on biologics and other small-molecule systemic agents, as well as share our personal experiences with the pharmacological management of HS in the clinical setting. Continued challenges that limit our ability to study and treat this disease effectively include a lack of a universally employed scoring system for disease severity, high variability in clinical presentation, high cost of off-label therapy, and the scarcity of long-term studies on treatment response and medication safety.

Eosinophilic annular erythema treated with dupilumab

Eosinophilic annular erythema is a rare, benign, recurrent condition characterized by annular skin lesions, tissue eosinophilia, and resistance to a variety of treatments. There are fewer than 30 cases reported in the English literature, 7 of which are in children. We present a case of recurrent eosinophilic annular erythema in an adolescent that was successfully treated with dupilumab, an interleukin‐4 receptor alpha antagonist.

Response to ustekinumab in three pediatric patients with alopecia areata

Alopecia areata (AA) is relatively common and can have a significant impact on quality of life, especially in a pediatric population. Currently available treatments are often ineffective or have poor safety profiles. Recent studies have highlighted the importance of the Th1 pathway in the pathogenesis of AA, suggesting ustekinumab as a treatment modality for this disease. We present three pediatric AA patients who demonstrated hair regrowth after initiating ustekinumab.

Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib: A 32-week open-label extension study with optional narrow-band ultraviolet B

To the Editor: Janus kinase inhibitors have shown promise in the treatment of vitiligo. In our original trial of topical ruxolitinib cream, the response was predominantly seen in facial vitiligo. We carried out a 32-week extension with an objective to determine if continued use of topical ruxolitinib would cause repigmentation in locations that previously did not respond. The primary end-point was an improvement in Vitiligo Area Scoring Index (VASI) at 52 weeks. The study was approved by the Tufts institutional review board and was conducted with the same methodology as the original trial. Patients continued to be treated with twice-daily application of topical ruxolitinib 1.5% cream on areas predetermined at baseline. Application of the cream was limited to 10% of the body surface area or 3.75 g/application. On the basis of previous evidence for synergism of Janus kinase inhibitors and ultraviolet light, concomitant narrow band ultraviolet B (NB-UVB) treatment was permitted.