Abstract
BackgroundModerate to severe psoriasis is a systemic inflammatory disease associated with insulin resistance, obesity and type 2 diabetes (T2DM). Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that improves glycaemia and has a marketing authorisation for the treatment of T2DM. Non-immunosuppressive therapies that are effective for psoriasis and its associated comorbidities would be a significant advance in the treatment of this chronic disease.Methods/DesignThis is a single centre, 39-week, prospective, randomised, open label, clinical trial of oral sitagliptin (Januvia®) in psoriasis patients who are due to undergo a course of narrow-band ultraviolet-B (NB-UVB) phototherapy. We plan to enrol 120 participants and allocate participants on a random and 1:1 basis to receive sitagliptin 100 mg daily for 24 weeks combined with NB-UVB or NB-UVB monotherapy. Participants will be followed up for 12 weeks after sitagliptin therapy is discontinued. The primary endpoint is the change in Psoriasis Area and Severity Index (PASI) 24 weeks after treatment initiation. Secondary endpoints include cumulative NB-UVB dose, number of NB-UVB treatments required to clear psoriasis, proportions of participants who achieve PASI-50 (50 % reduction in PASI from baseline), PASI-75, PASI-90 and the proportion of participants who relapse in each group. We will also analyse changes in cardiovascular disease risk factors, serum cytokine and hormone levels and peripheral blood mononuclear expression of immune proteins at 24 and 36 weeks. A subgroup of participants will have skin biopsies taken and analysed for skin levels and expression of immune cells, receptors, hormones and immune proteins. The genetic or epigenetic profile that predicts best response to DPP-4 inhibitor therapy will be analysed. The safety endpoints include the rate and severity of adverse events.DiscussionThis is the first randomised clinical trial assessing dipeptidyl peptidase-4 inhibition therapy in psoriasis. We hypothesise that sitagliptin therapy in combination with NB-UVB improves psoriasis severity compared to NB-UVB monotherapy.Trial registrationClinicalTrials.gov Identifier NCT02347501 (Date of registration: 27 January 2015).
Highlights
Moderate to severe psoriasis is a systemic inflammatory disease associated with insulin resistance, obesity and type 2 diabetes (T2DM)
We hypothesise that sitagliptin therapy in combination with narrow-band ultraviolet-B (NB-UVB) improves psoriasis severity compared to NB-UVB monotherapy
Psoriasis is characterised by keratinocyte hyperproliferation, by aberrant keratinocyte differentiation and by cutaneous inflammation [10]
Summary
Moderate to severe psoriasis is a systemic inflammatory disease associated with insulin resistance, obesity and type 2 diabetes (T2DM). Non-immunosuppressive therapies that are effective for psoriasis and its associated comorbidities would be a significant advance in the treatment of this chronic disease. Treatment options for severe psoriasis include systemic immunosuppressant therapies such as methotrexate and fumaric acid esters which are effective but associated with potential toxicities. Moderate to severe psoriasis is associated with smoking, alcohol excess, obesity and type 2 diabetes (T2DM) [5]. These comorbidities likely contribute to increased cardiovascular risk and premature mortality [6] as does the systemic inflammation associated with psoriasis [7]. An effective treatment for psoriasis that is non-immunosuppressive and treats comorbidities such as diabetes would, be very welcome
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