sitagliptin-phosphate and Psoriasis

Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor licensed for the treatment of type 2 diabetes mellitus (T2DM), has been reported to improve psoriasis.. We compared the effects of sitagliptin treatment, a DPP-4 inhibitor, in combination with narrow-band ultraviolet-B (NB-UVB) phototherapy compared to NB-UVB alone on psoriasis severity, quality of life, cardiovascular disease risk factors and immune parameters in people with moderate psoriasis without T2DM.. In this 39-week, single-centre, randomised controlled trial, people were allocated randomly to receive sitagliptin for 24 weeks with NB-UVB or NB-UVB alone. The primary endpoint was the change in Psoriasis Area and Severity Index (PASI) from baseline to 24 weeks. We estimated that 120 participants would be needed to have 80% power to find a significant difference between the groups.. A total of 118 patients were randomised. The median (IQR) baseline PASI was 8.8 (7.5-11.6). At 24 weeks, the mean difference from baseline in PASI (-1.0 [95% CI -2.0 to 0.0]) was significantly larger in the sitagliptin/NB-UVB arm than in the NB-UVB-alone arm (p = 0.044). There were significant differences in the change in Hospital Anxiety and Depression Scale (-2.5 [95% CI -4.0 to -1.0]; p = 0.002) and EuroQol 5-item questionnaire (0.1 [95% CI 0.0-0.1]; p = 0.036) values from baseline to 24 weeks between the sitagliptin/NB-UVB and the NB-UVB-alone arm. There were no treatment-related serious adverse events.. Sitagliptin therapy combined with NB-UVB phototherapy significantly improved psoriasis severity, albeit modestly, compared to NB-UVB phototherapy alone in patients with moderate psoriasis without T2DM.

Topics: Adult; Combined Modality Therapy; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Male; Middle Aged; Psoriasis; Severity of Illness Index; Sitagliptin Phosphate; Treatment Outcome; Ultraviolet Therapy

Moderate 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.. This 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.. This 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.. ClinicalTrials.gov Identifier NCT02347501 (Date of registration: 27 January 2015).

Topics: Clinical Protocols; Dipeptidyl-Peptidase IV Inhibitors; Humans; Prospective Studies; Psoriasis; Quality Control; Sample Size; Sitagliptin Phosphate; Ultraviolet Therapy

A patient with a 17-year history of plaque psoriasis accompanied by type 2 diabetes mellitus discontinued cyclosporine and steroid ointment given for treatment of psoriasis because she was dissatisfied with the effects of the drugs. After sitagliptin, a dipeptidyl peptidase-IV (DPP-IV) inhibitor, was administered for control of blood glucose, psoriatic skin lesions were gradually diminished, although HbA1c did not improve. Three months after the administration of sitagliptin, infiltration, scales and erythema on all psoriatic plaques disappeared, leaving pigmentation on flat skin. DPP-IV in serum degrades the incretin hormones which stimulate β-cell insulin secretion. DPP-IV inhibitors, as incretin enhancers, cause an increase in glucose-dependent insulin secretion, and are applied for the treatment of diabetes mellitus. DPP-IV is also expressed on T cells as CD26, a surface antigen which plays an important role in activating T cells. As helper T cells are involved in the pathogenesis of psoriasis, it is possible that DPP-IV inhibitors improve psoriatic skin lesions by inhibiting T cell activation, independently of glycemic control. DPP-IV inhibitors could be an alternative for the treatment of psoriasis.

Topics: Adult; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Hypoglycemic Agents; Psoriasis; Pyrazines; Sitagliptin Phosphate; T-Lymphocytes; Treatment Outcome; Triazoles

Psoriatic patients have a higher prevalence of diabetes mellitus type 2 (DM). Since dipeptidyl peptidase IV (DPP-IV) dysregulation is present in DM and psoriasis, DPP-IV inhibitors have been proposed as therapeutic agents for both conditions. We report a psoriasiform eruption induced by sitagliptin, a DPP-IV inhibitor. The role of DPP-IV in the pathogenesis of DM is well established; however data on psoriatic patients is contradictory. More studies are required to elucidate the effect of DPP-IV inhibitors and their relationship with DM and psoriasis.

Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Eruptions; Extremities; Female; Humans; Middle Aged; Psoriasis; Pyrazines; Sitagliptin Phosphate; Torso; Triazoles