Biological Retention Rates, the Reasons of Switching, and Prognostic Factors in Patients with Psoriasis Treated Biologics.

OBJECTIVE: To review patients who were treated at Tokai University Hospital with biologic agents for psoriasis vulgaris and psoriatic arthritis and analyze the biological retention rate, reasons for switching biologics, and investigate possible clinical prognostic factor which may affect whether a patient preferred one biologic to another. METHODS: Clinical courses of 63 patients who received biologic agents between Sep of 2010 to June of 2019 were investigated. Biological retention rate of each biologic agents, reasons of switching to another biologic agent, and prognostic factors, if any, between switched and non-switched patients were examined. RESULTS: The biological retention rate of ustekinumab (UST) was significantly longer than that of infliximab (IFX) or adalimumab (ADA). The major reason of switching was due to secondary loss of efficacy. Patients being treated with UST were more likely to switch to another biologic when they exhibited nail lesions. CONCLUSION: These results suggested that biological retention rate of UST was superior than that of IFX or ADA. Furthermore, with patients administered UST, nail symptom suggested possible clinical prognostic factor for switching to other biologic agents.

Health Economic Consequences of a Tightly Controlled Dose Reduction Strategy for Adalimumab, Etanercept and Ustekinumab Compared with Standard Psoriasis Care: A Cost-utility Analysis of the CONDOR Study.

A dose reduction strategy for adalimumab, etanercept and ustekinumab in patients with psoriasis who have stable and low disease activity has recently been compared with usual care in the CONDOR study (CONtrolled DOse Reduction) of biologics in patients with psoriasis with low disease activity. The aim of the current study was to perform a cost-utility analysis with a 12-month time horizon alongside this trial, using prospectively measured healthcare costs and quality-adjusted life years, based on Short-Form Six-Dimension utilities. Bootstrap analys-es were used to calculate the decremental cost-utility ratio and the incremental net monetary benefit. The dose reduction strategy resulted in a mean cost saving of €3,820 (95th percentile -€3,099 to -€4,509) per patient over a period of 12 months. There was an 83% chance that dose reduction would result in a reduction in quality adjusted life years (mean -0.02 (95th percentile -0.06 to 0.02). In conclusion, dose reduction of biologics resulted in substantial cost savings with an acceptable reduction in quality of life.

Assessment of Body Weight Changes in Patients with Inflammatory Bowel Diseases Initiating Biologic Therapy: A Prospective Cohort Study.

BACKGROUND: Prior studies have inconsistently suggested that biologic therapy may be associated with weight gain in inflammatory bowel disease patients (IBD). Our aim was to compare weight gain across different biologic therapy classes with distinct mechanisms of action. METHODS: This prospective cohort study recruited patients with moderate to severe IBD initiating outpatient biologic therapy with anti-TNF (infliximab, adalimumab), vedolizumab, or ustekinumab. Weight measurements were performed at weeks 0, 14, 30, and 54. Changes in weight between baseline and each of the follow-up visits were modeled as a continuous variable, and multivariate regression assessed the independent effect of therapeutic class on this outcome. RESULTS: Our study enrolled 269 patients (163 CD, 106 UC) initiating biologic therapy [99 anti-TNF (37%), 122 vedolizumab (45%), 48 ustekinumab (18%)]. From baseline, the weight significantly increased at week 14 with a mean of 0.36 kg (± 3.8 kg, p = 0.004) and continued to increase compared to baseline with 0.96 kg (± 3.9 kg, p < 0.001) and 1.29 kg (± 4.2 kg, p < 0.001) at week 30 and 54, respectively. On univariate and multivariable analysis, no significant differences between any of the biologic therapies for weight gain were seen at any time point (weight gain anti-TNF: 0.31 kg, 1.06 kg, 1.33 kg; VDZ: 0.30 kg, 0.83 kg, 1.10 kg; UST: 0.63 kg, 1.21 kg, 2.31 kg at wk 14, wk 30, and wk 54, respectively). None of the disease activity parameters showed any statistical association with weight gain. CONCLUSION: There was no difference in weight gain among the different biologic therapeutic classes.

Risk of malignancy with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment Registry.

BACKGROUND: The effect of systemic therapy on malignancy risk among patients with psoriasis is not fully understood. OBJECTIVE: Evaluate the impact of systemic treatment on malignancy risk among patients with psoriasis in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: Nested case-control analyses were performed among patients with no history of malignancy. Cases were defined as first malignancy (other than nonmelanoma skin cancer) in the Psoriasis Longitudinal Assessment and Registry, and controls were matched by age, sex, geographic region, and time on registry. Study therapies included methotrexate, ustekinumab, and tumor necrosis factor-α (TNF-α) inhibitors. Exposure was defined as 1 or more doses of study therapy within 12 months of malignancy onset and further stratified by duration of therapy. Multivariate conditional logistic regression, adjusted for potential confounders, was used to estimate odds ratios of malignancies associated with therapy. RESULTS: Among 12,090 patients, 252 malignancy cases were identified and 1008 controls were matched. Treatment with methotrexate or ustekinumab for more than 0 months to less than 3 months, 3 months to less than 12 months, or 12 months or longer was not associated with increased malignancy risk versus no exposure. Longer-term (≥12 months) (odds ratio, 1.54; 95% confidence interval, 1.10-2.15; P = .01), but not shorter-term treatment, with a TNF-α inhibitor was associated with increased malignancy risk. LIMITATIONS: Cases and controls could belong to 1 or more therapy categories. CONCLUSIONS: Long-term (≥12 months) treatment with a TNF-α inhibitor, but not methotrexate and ustekinumab, may increase risk for malignancy in patients with psoriasis.

A safety assessment of biological therapies targeting the IL-23/IL-17 axis in inflammatory bowel diseases.

INTRODUCTION: Many different compounds targeting the interleukin 23/17 axis have been developed and successfully studied in several autoimmune diseases, including inflammatory bowel diseases. Nevertheless, interfering with key immunological pathways raises potential safety concerns. This review focuses on the safety profile of these novel biological therapies. Areas covered: A literature search until March 2017 was performed to collect safety data on different compounds targeting this pathway, with emphasis on ustekinumab and secukinumab. Firstly, the authors discuss briefly how genetics can inform about potential safety issues. Secondly, they extensively describe safety issues (common adverse events, infections, malignancies…), immunogenicity, exposure to ustekinumab in specific populations and provide advice for vaccination. Finally, they address safety profiles of secukinumab and other biological targeting the IL-23/17 axis in IBD. Expert opinion: Current evidence suggests that ustekinumab therapy overweigh the potential drug-related risks. Additional safety data beyond randomized-controlled trials, derived from statistically powered, large prospective studies with long-term follow-up are urgently needed to assess the real-life ustekinumab-related risks and to establish the correct position of these novel class of biologicals in IBD treatment. Combining immunomodulators with ustekinumab seems to be safe, though prospective data specifically addressing this topic are currently missing. Similarly, the combination of different biological therapies still has to be studied.

To test or not to test? An updated evidence-based assessment of the value of screening and monitoring tests when using systemic biologic agents to treat psoriasis and psoriatic arthritis.

BACKGROUND: Safety profiles of systemic biologic agents for the treatment of psoriasis and psoriatic arthritis (PsA) encompass a wide spectrum of adverse events. To date, no uniform evidence-based guidelines exist regarding screening and monitoring patients who are undergoing biologic therapy. OBJECTIVE: We sought to identify studies evaluating screening and monitoring tests in the treatment of psoriasis and PsA with systemic biologic agents, and to propose evidence-based practical guidelines. METHODS: The MEDLINE database was searched to identify data on risks associated with adalimumab, etanercept, infliximab, and ustekinumab. Articles were reviewed and graded according to methods developed by the US Preventative Services Task Force. RESULTS: Evidence was strongest (grade B) for tuberculosis screening. Interferon-gamma release assay was preferable to tuberculin skin testing. Among known hepatitis B virus carriers, the evidence grade was C for monitoring liver function tests and viral load. LIMITATIONS: This study was limited by the lack of high-quality controlled trials evaluating screening and monitoring tests in patients treated with biologic agents. CONCLUSIONS: Baseline tuberculosis testing remains the only screening test with strong evidence to support its practice. Other screening and monitoring tests commonly performed in patients who are taking biologic agents are supported only in certain clinical settings or lack evidence to support or recommend against their practice.

Safety Surveillance for Ustekinumab and Other Psoriasis Treatments From the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: Safety surveillance is needed for biologic therapies for psoriasis. OBJECTIVE: To assess the risk of adverse events of special interest (AEoSIs) with ustekinumab and other psoriasis treatments in a real-world setting using 2014 Psoriasis Longitudinal Assessment and Registry (PSOLAR) data. AEoSIs included malignancy (excluding nonmelanoma skin cancer), major adverse cardiovascular events (MACE), serious infection, and all-cause mortality. METHODS: Cumulative rates of AEoSIs/100 patient-years (PY) are reported for ustekinumab, infliximab, other biologics (mostly adalimumab/etanercept), and non-biologics based on pre-specified analyses using attribution rules biased against ustekinumab. Risk factors for AEoSIs, including treatments, were determined using multivariate statistical analysis. RESULTS: A total of 12,093 patients (40,388 PY) were enrolled in PSOLAR. Overall incidence rates were 0.68/100PY for malignancy, 0.33/100PY for MACE, 1.60/100PY for serious infection, and 0.46/100PY for mortality. Unadjusted rates of serious infection for infliximab (2.91/100PY) and other biologics (1.91/100PY) were numerically higher compared with ustekinumab (0.93/100PY). Exposure to the combined group of biologics other than ustekinumab was significantly associated with serious infection (hazard ratio=1.96, P<.001). None of the biologics was associated with increased risk of malignancy, MACE, or mortality. LIMITATIONS: Observational data have inherent biases. CONCLUSION: Analysis of 2014 PSOLAR data identified no increased risk of malignancy, MACE, serious infection, or mortality with ustekinumab.