Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Long-term Safety of Oral Systemic Therapies for Psoriasis: A Comprehensive Review of the Literature.

Oral systemic therapies are important treatment options for patients with moderate-to-severe psoriasis, either as monotherapy or in therapy-recalcitrant cases as combination therapy with phototherapy, other oral systemics or biologics. Long-term treatment is needed to maintain sufficient disease control in psoriasis, but continuous use of systemic treatments is limited by adverse events (AEs) and cumulative toxicity risks. The primary aim of this comprehensive literature review was to examine the long-term safety profiles of oral agents commonly used in the treatment of adults with psoriasis. Searches were conducted in EMBASE and PubMed up to November 2018, and 157 relevant publications were included. Long-term treatment with acitretin could be associated with skeletal toxicity and hepatotoxicity, although evidence for skeletal toxicity is mixed and hepatotoxicity is rare, particularly at low doses. Other safety issues include hyperlipidaemia and potential for teratogenicity up to 2-3 years after discontinuation of treatment. There is a paucity of data on long-term treatment with apremilast. Continued exposure to apremilast does not seem to increase the incidence of common AEs, such as gastrointestinal (GI) AEs, upper respiratory tract infections and headache, while the long-term risks for depression, suicidal thoughts and weight loss are unknown. Long-term ciclosporin treatment is associated with renal toxicity, hypertension, non-melanoma skin cancer, neurological AEs and GI AEs. Long-term methotrexate treatment is associated with hepatotoxicity, GI AEs, haematological toxicity, renal toxicity and alopecia. Finally, long-term treatment with fumaric acid esters (FAE) is associated with GI AEs, flushing, lymphocytopenia, proteinuria and elevated liver enzymes. Median drug survival estimates varied considerably: ~ 2.9-9.7 months for apremilast; ~ 5.4 months for ciclosporin; ~ 8.6 months for acitretin; ~ 12.1-21.6 months for methotrexate; and ~ 54.8 months for FAE. These long-term safety profiles may help to guide clinicians to select the optimal oral systemic treatment for the long-term treatment of psoriasis in adults.

Extraparietal or lymphatic late relapse of neoplasms: confirmation by means of EUS-FNA key for the treatment.

BACKGROUND: After treatment intended to cure systemic neoplasms, a series of monitoring strategies are followed. OBJECTIVE: To analyse our experience in confirming the cases of lymphatic or extraparietal relapse in areas accessible to endoscopic ultrasonography plus fine-needle aspiration (EUS-FNA) in long-term monitoring (>1 year of treatment for the primary neoplasm) and define what implications have been derived with regards histopathological confirmation in relation to treatment. MATERIALS AND METHODS: Retrospective analysis was made of all EUS-FNA carried out in our Endoscopy Unit during the period from 1/07/2007 to 28/02/2010 by means of searches in the Endobase (Olympus) database. Medical records of patients and drug therapy were reviewed in order to check the chemotherapy used in each case. RESULTS: From a total of 154 EUS-FNA carried out in our service, we have detected histopathological confirmation of malignancy in primary neoplasm treated with initial curative intention at least 1 year before. Locations were: esophageal extraparietal involvement of a squamous cell carcinoma (one patient), perirectal adenopathy of rectal adenocarcinoma (one patient), multiple lymphatic relapse of melanoma (two patients), perigastric adenopathy relapse of gastric adenocarcinoma (one patient), pancreatic head mass secondary to initial breast ductal carcinoma (one patient). In all cases, this fact has involved a directed treatment: surgery (one patient), radiotherapy (one patient), chemotherapy (four patients). CONCLUSIONS: Confirmation by means of EUS-FNA of late relapse in any section of the digestive tract allowed a treatment to be carried out by surgery, radiotherapy, or chemotherapy.