The risk of malignancy in patients with secukinumab-treated psoriasis, psoriatic arthritis and ankylosing spondylitis: analysis of clinical trial and postmarketing surveillance data with up to five years of follow-up.

BACKGROUND: Data on the use of biologic therapy and malignancy risk are inconsistent due to limited long-term robust studies. OBJECTIVES: To assess the malignancy risk in patients with secukinumab-treated psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS). METHODS: This integrated safety analysis from both the secukinumab clinical trial programme and postmarketing safety surveillance data included any patient receiving at least one approved dose of secukinumab with a maximum of 5 years of follow-up. Safety analyses evaluated the rate of malignancy using exposure-adjusted incidence rates [EAIR; incidence rates per 100 patient treatment-years (PTY)]. Standardized incidence ratios (SIRs) were reported using the Surveillance, Epidemiology, and End Results Program (SEER) database as a reference population. Crude incidence of malignancy was also reported using postmarketing surveillance data. RESULTS: Safety data from 49 clinical trials with secukinumab-treated patients were included: 10 685 patients with psoriasis, 2523 with PsA and 1311 with AS. Across indications over a 5-year period, the EAIR of malignancy was 0·85 per 100 PTY [95% confidence interval (CI) 0·74-0·98] in secukinumab-treated patients, corresponding to 204 patients per 23 908 PTY. Overall, the observed vs. expected number of malignancies from secukinumab clinical trial data were comparable, as indicated by an SIR of 0·99 (95% CI 0·82-1·19) across indications. The estimated crude cumulative incidence reporting rate per 100 PTY for malignancy was 0·27 in the postmarketing surveillance data across indications with a cumulative exposure of 285 811 PTY. CONCLUSIONS: In this large safety analysis, the risk of malignancy was low for up to 5 years of secukinumab treatment. These data support the long-term use of secukinumab in these indications.

Effect of fibrosis on adverse events in patients with hepatitis C treated with telaprevir.

BACKGROUND: Data about adverse events are needed to optimise telaprevir-based therapy in a broad spectrum of patients. AIM: To investigate adverse events of telaprevir-based therapy in patients with and without advanced fibrosis or cirrhosis in a real-world setting. METHODS: Data on 174 hepatitis C-infected patients initiating telaprevir-based therapy at Mount Sinai and Montefiore medical centres were collected. Biopsy data and FIB-4 scores identified patients with advanced fibrosis. Multivariable fully adjusted models were built to assess the effect of advanced fibrosis on specific adverse events and discontinuation of treatment due to an adverse event. RESULTS: Patients with (n = 71) and without (n = 103) advanced fibrosis were similar in BMI, ribavirin exposure, gender, prior treatment history, haemoglobin and creatinine, but differed in race. Overall, 47% of patients completed treatment and 40% of patients achieved SVR. Treated patients with and without advanced fibrosis or cirrhosis had similar rates of adverse events; advanced fibrosis, however, was independently associated with ano-rectal discomfort (P = 0.03). Three patients decompensated and had advanced fibrosis. The discontinuation of all treatment medications due to an adverse event was significantly associated with older age (P = 0.01), female gender (P = 0.01) and lower platelets (P = 0.03). CONCLUSIONS: Adverse events were common, but were not significantly related to the presence of advanced fibrosis or cirrhosis. More critical monitoring in older and female patients with low platelets throughout treatment may reduce adverse event-related discontinuations.

Use of Tris-hydroxymethyl aminomethane in severe lactic acidosis due to highly active antiretroviral therapy: a case report.

BACKGROUND: Lactic acidosis is a rare, yet life-threatening adverse drug effect of highly active antiretroviral therapy (HAART), specifically stavudine and lamivudine. These nucleoside analogue reverse transcriptase inhibitors (NRTIs) are commonly used to treat patients infected with the human immunodeficiency virus (HIV). CASE: We report the use of Tris-hydroxymethyl aminomethane (THAM) to treat severe lactic acidosis due to HAART in a 50-year-old African-American woman. NRTIs can cause hyperlactinaemia by interfering with mitochondrial oxidative phosphorylation function, which normally removes H(+) generated by the hydrolysis of adenosine triphosphate. This side-effect is associated with a high mortality in patients infected with HIV. One explanation for this high mortality is that lactic acidosis is typically refractory to treatment with commonly used buffering agents. CONCLUSION: THAM generates serum bicarbonate, and reduces the level of carbon dioxide in arterial blood. Both of these qualities appear to make THAM an ideal agent for treating lactic acidosis caused by HAART.