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.

Drug survival and safety of biosimilars and originator adalimumab in the treatment of psoriasis: a multinational cohort study.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease. Adalimumab is an effective but previously expensive biological treatment for psoriasis. The introduction of biosimilars following the patent expiry of the originator adalimumab Humira has reduced the unit cost of treatment. However, the long-term effectiveness and safety of adalimumab biosimilars for treating psoriasis in real-world settings are uncertain and may be a barrier to widespread usage. METHODS AND ANALYSIS: This study aims to compare the drug survival and safety of adalimumab biosimilars to adalimumab originator for the treatment of psoriasis. We will use both routinely collected healthcare databases and dedicated pharmacovigilance registries from the PsoNet initiative, including data from the UK, France and Spain. We will conduct a cohort study using a prevalent new user design. We will match patients on previous adalimumab exposure time to create two equal-sized cohorts of biosimilar and originator users. The coprimary outcomes are drug survival, defined by the time from cohort entry to discontinuation of the drug of interest; and risk of serious adverse events, defined by adverse events leading to hospitalisation or death. Cox proportional hazards models will be fitted to calculate HRs as the effect estimate for the outcomes. ETHICS AND DISSEMINATION: The participating registries agree with the Declaration of Helsinki and received approval from local ethics committees. The results of the study will be published in scientific journals and presented at international dermatology conferences by the end of 2023.

Effectiveness and safety of Methotrexate in psoriasis: an eight-year experience with 218 patients.

BACKGROUND: Methotrexate (MTX), a traditional antipsoriatic drug, is very frequently used either as monotherapy or in combination with other systemic drugs. OBJECTIVES: To assess the effectiveness and safety of MTX in psoriasis in usual clinical practice. METHODS: We conducted a retrospective study. We performed an electronic and manual chart review of patients treated with MTX in the Psoriasis Unit of our Hospital from January 2007 to December 2014. Demographic and clinical data, PASI/DLQI scores and reasons for suspension of all patients treated with MTX in usual clinical practice were recorded. RESULTS: Two hundred and eighteen patients were included. MTX was administered in 67% of cases as the first systemic treatment. The average treatment duration was 17.2 ± 13.6 months. All patients were subjected to clinical and laboratory monitoring. About 33.5% of them achieved a reduction of 75% or more of the initial PASI at week 12, 34.9% at week16, 44.7% at week 24, and 52.8% at week 48. A 3.3% had to discontinue the therapy due to analytical hepatic (2.8%) or renal (0.5%) abnormalities. Only one patient experienced severe interstitial pneumonitis and none required liver biopsy. CONCLUSIONS: MTX is an effective and safe option for the treatment of psoriasis in the real-world clinical practice.

Maternal obesity in early pregnancy and risk of adverse outcomes.

OBJECTIVES: To assess the role of the health consequences of maternal overweight and obesity at the start of pregnancy on gestational pathologies, delivery and newborn characteristics. METHODS: A cohort of pregnant women (n = 6.558) having delivered at the Maternal & Child University Hospital of Gran Canaria (HUMIGC) in 2008 has been studied. Outcomes were compared using multivariate analyses controlling for confounding variables. RESULTS: Compared to normoweight, overweight and obese women have greater risks of gestational diabetes mellitus (RR = 2.13 (95% CI: 1.52-2.98) and (RR = 2.85 (95% CI: 2.01-4.04), gestational hypertension (RR = 2.01 (95% CI: 1.27-3.19) and (RR = 4.79 (95% CI: 3.13-7.32) and preeclampsia (RR = 3.16 (95% CI: 1.12-8.91) and (RR = 8.80 (95% CI: 3.46-22.40). Obese women have also more frequently oligodramnios (RR = 2.02 (95% CI: 1.25-3.27), polyhydramnios. (RR = 1.76 (95% CI: 1.03-2.99), tearing (RR = 1.24 (95% CI: 1.05-1.46) and a lower risk of induced deliveries (RR = 0.83 (95% CI: 0.72-0.95). Both groups have more frequently caesarean section (RR = 1.36 (95% CI: 1.14-1.63) and (RR = 1.84 (95% CI: 1.53-2.22) and manual placenta extraction (RR = 1.65 (95% CI: 1.28-2.11) and (RR = 1.77 (95% CI: 1.35-2.33). Newborns from overweight and obese women have higher weight (p<0.001) and a greater risk of being macrosomic (RR = 2.00 (95% CI: 1.56-2.56) and (RR = 2.74 (95% CI: 2.12-3.54). Finally, neonates from obese mother have a higher risk of being admitted to special care units (RR = 1.34 (95% CI: 1.01-1.77). Apgar 1 min was significantly higher in newborns from normoweight mothers: 8.65 (95% CI: 8.62-8.69) than from overweight: 8.56 (95% CI: 8.50-8.61) or obese mothers: 8.48 (95% CI: 8.41-8.54). CONCLUSION: Obesity and overweight status at the beginning of pregnancy increase the adverse outcomes of the pregnancy. It is important to promote the normalization of bodyweight in those women who intend to get pregnant and to provide appropriate advice to the obese women of the risks of obesity at the start of the pregnancy.

Correction: Maternal Obesity in Early Pregnancy and Risk of Adverse Outcomes.

[This corrects the article DOI: 10.1371/journal.pone.0080410.].

[Prevalence of obesity in pregnant women of Canary Islands, Spain]. / Prevalencia de obesidad en la población gestante de Gran Canaria.

BACKGROUND AND OBJECTIVE: Different epidemiological studies have shown that maternal excess of weight during pregnancy is associated with adverse outcomes of pregnancy, childbirth and morbidity of the neonate. Prevalence of obesity in a pregnant population of Canary Islands is reported here. SUBJECTS AND METHODS: The group studied was an integrated cohort of all the pregnant women being followed-up at the Materno-Infant University Hospital of the Canarias [Hospital Universitario Materno-Infantil de Canarias; HUMIC] and who concluded their gestation during the year 2008 (n=6693). BMI was measured at the beginning of the pregnancy. RESULTS: 25.0% of the sample of pregnant women were overweight and 17.1% were obese, increasing both with age and not influenced with the educational level. CONCLUSIONS: The prevalence of obesity and overweight among pregnant women from the Canary Islands is high. Among the values available from other European countries, only the UK reported values greater than our study sample.