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 nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.

BACKGROUND: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. OBJECTIVE: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. METHODS: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. RESULTS: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5). LIMITATIONS: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. CONCLUSION: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.

Association between clinical factors and dose modification strategies in the treatment with ustekinumab for moderate-to-severe plaque psoriasis.

PURPOSE: The aim of this study was to identify clinical factors associated with dose reduction and dose escalation in the treatment with ustekinumab in patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: An observational, longitudinal and retrospective study was conducted using patients with moderate-to-severe plaque psoriasis. We reviewed clinical histories and variables were recorded on a database (patients' characteristics, pharmacotherapeutics, effectiveness and safety). We evaluated correlation between dose reduction, dose escalation and used dose with other variables. RESULTS: Of the study's 62 patients, Ustekinumab dose was adjusted in 45.2% (22.6% with reduced doses and 22.6% with increased doses). We found a statistically significant correlation between extending the dosing interval and the absence of psoriatic arthritis, no concomitant systemic therapies, treatment time with ustekinumab, lower PASI at week 28 and achieving PASI75 at week 28. There was also a statistically significant correlation between dose escalation and diabetes mellitus, psoriatic arthritis, prior biological treatments, concomitant systemic therapies, concomitant phototherapy and not achieving PASI75 at week 28. CONCLUSIONS: Dose-reduction strategies would increase ustekinumab efficiency in patients that achieve PASI 75 without psoriatic arthritis, diabetes mellitus, previous BT and concomitant treatment with conventional systemic drugs.

Efficiency of biological therapies in patients with moderate to severe psoriasis: impact of a pharmacotherapeutic protocol.

BACKGROUND: It is not clear how to best use biologics in the treatment of psoriasis. Our objective was to assess use of a protocol for biological therapies (BT) in psoriasis. METHODS: A consensus protocol was established that included the indications for BT and dose optimization. Patient's characteristics, effectiveness, and cost of BT were analyzed before and after the implementation with two cross-sectional studies to assess its impact. RESULTS: About 106 were treated before the protocol and 118 patients were treated after. After implementing the protocol, the dose was reduced in 43.4% of the patients receiving adalimumab, in 37.5% for etanercept, in 28.6% for infliximab, and in 14.7% for ustekinumab. No statistically significant differences were found in PASI score after the implementation of the protocol, except for the percentage of patients that achieved PASI 75 with ustekinumab, which was slightly higher. The global yearly savings achieved with the protocol implementation were 115,969 €. CONCLUSIONS: The protocol helped to increase the efficiency of BT, with decreasing doses of BT without affecting treatment effectiveness.