Dermatology

Bissonnette, R., M. Luchi, R. Fidelus-Gort, S. Jackson, H. Zhang, R. Flores, R. Newton, P. Scherle, S. Yeleswaram, X. Chen and A. Menter (2016). “A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis.” J Dermatolog Treat: 1-7.

Full text of this article.

BACKGROUND: Chronic plaque psoriasis is partially mediated by elevation of proinflammatory cytokines, including several within the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. OBJECTIVE: To evaluate the safety and efficacy of the oral selective JAK1 inhibitor INCB039110 in stable, chronic plaque psoriasis. METHODS: This was a phase 2, randomized, double-blind, placebo-controlled, dose-escalation study of INCB039110 (100 mg once daily, 200 mg once daily, 200 mg twice daily and 600 mg once daily) for 28 days. The primary endpoint was mean percent change from baseline in the static Physician Global Assessment (sPGA) at day 28. The protocol was institutional review board approved. RESULTS: Of 50 patients, 48 completed the study. At day 28, mean percent reduction from baseline in sPGA was 22.2% for INCB039110 100 mg once daily (p = 0.270 vs. placebo), 29.4% for 200 mg once daily (p = 0.118), 35.2% for 200 mg twice daily (p = 0.053), 42.4% for 600 mg once daily (p = 0.003) and 12.5% for placebo. Across groups, 11.1% to 45.5% achieved an sPGA score of 1 versus 0% for placebo. INCB039110 was generally well tolerated; the most common treatment-emergent adverse event was nasopharyngitis (18.4%). CONCLUSION: INCB039110 produced significant improvements in sPGA, demonstrating proof of concept in chronic plaque psoriasis.

Zaghi, D., C. Weir, J. Ying, C. Carlin, T. Greene, R. DeShazo, K. Callis Duffin and G. G. Krueger (2016). “Desired Improvement Tool (DIT): A tool to assess desire for improvement in psoriasis patients.” J Dermatolog Treat 27(1): 27-30.

Full text of this article.

No validated instrument exists to measure desire for improvement in psoriasis patients. To address this void, we conducted a single-center longitudinal study of 268 moderate-to-severe psoriasis patients to psychometrically validate the Desired Improvement Tool (DIT). The DIT is a single-item instrument scored 0-5 by the patient. A 0 indicates the patient is satisfied with disease level and does not desire further treatment. A 5 indicates a large amount of improvement is desired. The DIT demonstrated high test-retest reliability (Spearman, r = 0.97). Predictive and construct validity were moderate-to-high: r = 0.70 for BSA, 0.67 for PASI, and 0.56 for PGA and r = 0.67 for Life Quality Assessment (LQA), respectively. A sensitivity analysis revealed the DIT responded to changes in BSA. As a psychometrically valid tool, the DIT may guide clinical management of psoriasis patients by capturing an important clinical construct in an expedient and quantifiable manner.

Tran, C., E. Wilder and J. R. Griffin (2015). “Stomatitis, Cutaneous Bullae, and Renal Failure.” JAMA-Journal of the American Medical Association 314(21): 2296-2297.

Full text of this article.

A 64-year-old African American woman presented to the emergency department for evaluation of bleeding mouth sores, tender crusted plaques on her scalp, and blisters on her skin. Three weeks previously, she noticed painful erosions throughout her mouth. A week later, painful blisters appeared on her upper extremities, trunk, and thighs. She also reported 2 pruritic and painful lesions on her scalp that had appeared 6 months prior, shortly after a chemical hair treatment. She had a history of alcohol, tobacco, cocaine, and marijuana use but denied current illicit drug use. She had not taken any medications prior to the appearance of the lesions. The patient reported a 2.25-kg weight loss, subjective fevers, and chills but no urinary symptoms. On admission, the patient was tachycardic (113/min), but she was afebrile and other vital signs were normal. Physical examination revealed crusted plaques on her scalp bilaterally (Figure). Erosive stomatitis involving the lower lip, buccal mucosa, hard palate, soft palate, and tongue was noted (Figure). Multiple well-circumscribed, round-to-oval bullae, erosions, and hyperpigmented patches were noted on her upper extremities, trunk, and thighs (Figure). Laboratory evaluation revealed a serum creatinine level of 7.1 mg/dL (627.6 μmol/L), up from a baseline (10 days prior) level of 0.9 mg/dL (79.6 μmol/L). Urinalysis revealed a specific gravity of 1.015 and was positive for hyaline casts and protein but negative for white blood cells, red blood cells, and bacteria. A complete blood cell count was unremarkable. Results of human immunodeficiency virus screen and urine drug screen were normal . . . A shave biopsy from a back lesion showed suprabasal acantholysis and bulla. Direct immunofluorescence testing of punch biopsies from the edges of lesions on the back and scalp showed intercellular deposition of IgG and C3 in the lower epidermis. Indirect immunofluorescence on monkey esophagus substrate revealed serum cell surface IgG antibodies. Testing with ELISA revealed elevated anti–Dsg 1 and anti–Dsg 3 antibodies (132 U and 187 U, respectively). Therapy was initiated with an oral anesthetic rinse, oral prednisone (60 mg daily), and topical corticosteroids. With intravenous fluid administration, the patient’s creatinine level corrected to 0.7 mg/dL (61.9 μmol/L), suggesting acute renal failure most likely attributable to decreased oral intake secondary to pain. The patient was discharged with follow-up in dermatology clinic to initiate azathioprine as an outpatient. (Excerpts from text; no abstract.)

Campa, M., B. Mansouri, R. Warren and A. Menter (2015). “A Review of Biologic Therapies Targeting IL-23 and IL-17 for Use in Moderate-to-Severe Plaque Psoriasis.” Dermatol Ther (Heidelb) 2015 Dec 29. [Epub ahead of print].

Full text of this article.

The development of several highly effective biologic drugs in the past decade has revolutionized the treatment of moderate-to-severe plaque psoriasis. With increased understanding of the immunopathogenesis of psoriasis, the emphasis has turned toward more specific targets for psoriasis drugs. Although the complex immunological pathway of psoriasis is not yet completely understood, current models emphasize the significant importance of interleukin (IL)-23 and IL-17. Several biologic drugs targeting these cytokines are now in various stages of drug development. Drugs targeting IL-23 include BI-655066, briakinumab, guselkumab, tildrakizumab, and ustekinumab. Drugs targeting IL-17 include brodalumab, ixekizumab, and secukinumab. While many of these have shown safety and good efficacy in clinical trials of moderate-to-severe plaque psoriasis, long-term safety is still to be established.