Long-term safety of Ixekizumab in adults with psoriasis, psoriatic arthritis, or axial spondyloarthritis: a post-hoc analysis of final safety data from 25 randomized clinical trials.

BACKGROUND: We report long-term, end-of-study program safety outcomes from 25 randomized clinical trials (RCTs) in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) [including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)] who received ≥ 1 dose of Ixekizumab (IXE) over 5 years (PsO) or up to 3 years (PsA, axSpA). METHODS: This integrated safety analysis consists of data from patients who received any dose of IXE, across 25 RCTs (17 PsO, 4 PsA, 4 axSpA). Rates of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and selected adverse events (AEs) of interest were analyzed for all pooled studies by years of therapy and overall, through March 2022. Results were reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) overall and at successive year intervals. RESULTS: Six thousand eight hundred ninety two adult patients with PsO, 1401 with PsA, and 932 with axSpA (including AS and nr-axSpA), with a cumulative IXE exposure of 22,371.1 PY were included. The most commonly reported TEAE across indications was nasopharyngitis (IRs per 100 PY: 8.8 (PsO), 9.0 (PsA), 8.4 (axSpA)). SAEs were reported by 969 patients with PsO (IR 5.4), 134 patients with PsA (IR 6.0), and 101 patients with axSpA (IR 4.8). Forty-five deaths were reported (PsO, n = 36, IR 0.2; PsA, n = 6, IR 0.3; axSpA, n = 3, IR 0.1). TEAEs did not increase during IXE exposure: IRs per 100 PY, PsO: 88.9 to 63.2 (year 0-1 to 4-5), PsA: 87 to 67.3 (year 0-1 to 2-3), axSpA: 82.1 to 55.4 (year 0-1 to > = 2). IRs per 100 PY of discontinuation from IXE due to AE were 2.9 (PsO), 5.1 (PsA), and 3.1 (axSpA). IRs per 100 PY of injection site reactions were 5.9 (PsO), 11.6 (PsA) and 7.4 (axSpA); Candida: 1.9 (PsO), 2.0 (PsA), and 1.2 (axSpA); depression, major adverse cerebro-cardiovascular events and malignancies: ≤ 1.6 across all indications. Adjudicated IRs per 100 PY of inflammatory bowel disease were ≤ 0.8 across indications (0.1 [PsO]; 0.1 [PsA]; 0.8 [axSpA]). CONCLUSIONS: In this integrated safety analysis, consisting of over 22,000 PY of exposure, the long-term safety profile of IXE was found to be consistent with previous, earlier reports, with no new safety signals identified. TRIAL REGISTRATION: NCT registration numbers for RCTs included in this integrated analysis can be found in Additional File 1.

Disease response and patient-reported outcomes among initiators of ixekizumab.

OBJECTIVES: There is limited real-world evidence on using ixekizumab in psoriasis patients. Therefore, we characterized patients with psoriasis initiating ixekizumab and report 6-month changes in disease and patient-reported outcomes. METHODS: Adult patients with psoriasis who initiated ixekizumab and completed a 6-month follow-up visit were enrolled from the Corrona Psoriasis Registry. Disease characteristics and outcomes were assessed at ixekizumab initiation. Outcomes included the mean 6-month change in Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator Global Assessment (IGA), and IGA*BSA. RESULTS: From baseline to follow-up in all patients (n = 136), means decreased for IGA*BSA (-45.5) and BSA (-12.4), and a higher % achieved an absolute PASI ≤ 5 (84.6%), BSA 0-3 (72.1%), and IGA 0/1 (50.7%). Within stratified groups, means decreased for PASI <12 for IGA*BSA (-21.1) and BSA (-6.3); PASI≥12 for IGA*BSA (-94.8) and BSA (-24.6); weight <100 kg for IGA*BSA (-45.1) and BSA (-12.4); weight ≥100 kg for IGA*BSA (-46.2) and BSA (-12.3); concomitant PsA for IGA*BSA (-56.0) and BSA (-15.3); and in no concomitant PsA for IGA*BSA (-36.9) and BSA (-10.0). CONCLUSIONS: We provide real-world evidence on the benefits of ixekizumab for treating psoriasis, regardless of baseline disease severity, weight, or concomitant PsA.

Injection Site Reactions in the Federal Adverse Event Reporting System (FAERS) Post-Marketing Database Vary Among Biologics Approved to Treat Moderate-To-Severe Psoriasis.

INTRODUCTION: Biologics used to treat moderate-to-severe plaque psoriasis may cause injection site reactions (ISRs) characterized by erythema, edema, itch, and sometimes pain. The Federal Adverse Event Reporting System (FAERS) is a repository of spontaneous post-marketing reports of adverse events (AEs) that are reported to the US Food and Drug Administration (FDA). Our objective was to perform a pharmacovigilance analysis of FAERS reports of ISRs associated with the use of subcutaneously administered biologic products approved to treat moderate-to-severe plaque psoriasis. METHODS: The products included in our assessment were adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab. Reports from the date of US approval for each biologic as treatment for plaque psoriasis through 2 years were included using the search term "injection site." RESULTS: The results show that the FAERS database contained reports of ISRs for all of the included biologics during the 2 years following FDA approval. The most common reports on ISRs were on pain, irritation, and erythema for adalimumab; reaction, pain, and erythema for etanercept; erythema, pain, and reaction for ixekizumab; bruising, pain, hemorrhage for secukinumab; and pain, induration, and swelling for ustekinumab. FAERS does not include data on total patient exposure; therefore, ISR rates could not be calculated. CONCLUSIONS: Specific ISRs varied among the biologic therapies assessed. The findings presented could be helpful when patients consider switching therapies due to ISRs. FUNDING: Eli Lilly and Company.

Racial and ethnic differences in psychotropic medication use among community-dwelling persons with dementia in the United States.

OBJECTIVES: Little is known about the patterns of psychotropic medication use in community-dwelling minority persons with dementia (PWD). The purpose of this study was to investigate racial/ethnic differences in psychotropic medication use across a diverse population of community-dwelling PWD and to examine the extent to which caregiver characteristics influence this use. METHOD: Data were drawn from the baseline assessment of the Resources for Enhancing Alzheimer's Caregiver Health II trial. Generalized linear models were used to identify racial/ethnic differences in psychotropic medication use. Akaike Information Criterion (AIC) model selection was used to evaluate possible explanations for observed differences across racial/ethnic group. RESULTS: Differences in anxiolytic and antipsychotic medication use were observed across racial/ethnic groups; however, race/ethnicity alone was not sufficient to explain those differences. Perceptions of caregiving and caregiver socioeconomic status were important predictors of anxiolytic use while PWD characteristics, including cognitive impairment, functional impairment, problem behavior frequency, pain, relationship to the caregiver, sex, and age were important for antipsychotic use. CONCLUSION: Racial/ethnic differences in psychotropic medication use among community-dwelling PWD cannot be explained by race/ethnicity alone. The importance of caregiver characteristics in predicting anxiolytic medication use suggest that interventions aimed at caregivers may hold promise as an effective alternative to pharmacotherapy.

Caregiver and care recipient characteristics as predictors of psychotropic medication use in community-dwelling dementia patients.

OBJECTIVES: The current practice of prescribing psychotropic medication for the management of dementia-related behavioral disturbances is under substantial debate. Using Pearlin's stress process model as theoretical underpinning, the aim of this investigation is to identify caregiver and care recipient characteristics as predictors of anxiolytic, antipsychotic, and antidepressant use among community-dwelling dementia patients. We hypothesized that caregiving burden and patient characteristics, particularly behavior disturbances and pain, would be positively associated with psychotropic medication use. METHODS: Data for this exploratory, cross-sectional study were drawn from the baseline assessment of the Resources for Enhancing Alzheimer's Caregiver Health II trial. Only participants with full baseline information were examined (N = 598). Caregiver characteristics, such as confidence managing problematic behaviors, and care recipient characteristics including pain, problem behaviors, cognitive impairment, and functional impairment, were examined in relation to care recipient psychotropic medication use. RESULTS: Contrary to our hypothesis, behavioral disturbances and burden associated with these disturbances were not significantly associated with psychotropic use. Rather, caregiver characteristics such as race and overall vigilance, and care recipient characteristics such as cognitive status, functional status, and pain were significantly associated with the use of psychotropic medication. Findings differed by class of medication. CONCLUSION: These exploratory findings suggest the utility of a holistic approach to understanding the factors associated with pharmacotherapy among community-dwelling elders with dementia. Significant associations between caregiver characteristics and care recipient psychotropic medication use suggest that educating caregivers in non-pharmacologic strategies hold promise for a more balanced biopsychosocial approach to maintaining dementia patients in the community.