Dementia Care Among United States Dialysis Providers: A Mixed Methods Study Evaluating Clinician Comfort and Knowledge.

Rationale & Objective: Given the high burden of dementia in dialysis patients, the dialysis workforce needs to be prepared to provide high-quality, person-centered dementia care. We explored comfort with and knowledge of dementia among US dialysis care providers. Study Design: Web-based survey. Setting & Participants: Emails were sent to National Kidney Foundation and National Association of Nephrology Technicians/Technologists membership listservs (September 26, 2022-October 22, 2022). In total, 1,121 respondents had complete data for analysis (57%, 35-49 years; 62% female; 62%/22% White/African American) including 81 physicians, 61 advanced practice providers, 230 nurse managers, 260 nurses, 202 social workers, 195 dietitians, and 86 dialysis patient care technicians. Exposures: Provider role, age, tenure, self-reported gender, previous dementia training, and awareness of dementia guidance. Outcomes: Dementia Knowledge (assessed using Dementia Knowledge Assessment Scale [DKAS; score range, 0-25]). Analytic Approach: Characteristics of respondents, comfort with dementia care, and dementia knowledge were summarized and tabulated overall and by role. Robust regression was used to obtain coefficients confidence intervals for the associations between characteristics and DKAS scores, adjusting for role and tenure. Free-text responses to an open-ended question about treating patients with dementia or cognitive impairment were analyzed using thematic analysis. Results: Dementia knowledge among US dialysis providers may be limited (overall DKAS score = 17; range, 13-21 across roles), despite most reporting knowing when patients had dementia (97%) and receiving training in dementia care (62%). Further, training may be inadequate: those who reported receiving dementia training had lower DKAS scores than those who reported not receiving training (ß, -3.9; 95% CI, -4.4 to -3.4). Thematic analysis of open-ended responses suggested that the impact of dementia on dialysis care and management and treatment beyond dialysis care are challenging for providers. Limitations: Data were self-reported and limited information was gathered about quality, content, and timing of dementia training received. Conclusion: Many US dialysis care providers had suboptimal dementia knowledge, despite reporting being comfortable with providing dementia care and reporting they received prior training. Qualitative findings indicate complexity among providers regarding comfort with and knowledge of treating patients with cognitive impairment. Targeted training for the dialysis workforce in dementia knowledge and best practices for person-centered dementia care is warranted.

There is a high burden of mild cognitive impairment and dementia in the US in-center hemodialysis setting. Although the prevalence of dementia is increasing, little is known about the readiness for the interdisciplinary team to provide person-centered, dementia-friendly patient care. Examining data from a US web-based survey, we found that providers felt confident in knowing when a patient had cognitive impairment, but less than two-thirds reported receiving training about dementia. Further, those who received training about dementia or had awareness of dementia guidelines had lower scores for dementia knowledge. This information can be used to develop training and guidance for interdisciplinary team to reduce staff burden and improve quality of care for patients living with cognitive impairment.

Progression of Coronary Artery Calcification and Risk of Clinical Events in CKD: The Chronic Renal Insufficiency Cohort Study.

RATIONALE & OBJECTIVE: Coronary artery calcification (CAC) progresses rapidly in people with chronic kidney disease (CKD) compared with the general population. We studied the association between CAC progression and higher risks of atherosclerotic cardiovascular disease (CVD), congestive heart failure, and all-cause mortality among adults with CKD. STUDY DESIGN: Prospective cohort study. SETTING: & Participants: 1,310 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had at least one CAC scan with no prior history of CVD and with observed or imputed data on changes in CAC over time. EXPOSURE: Observed or imputed CAC progression, categorized as incident CAC among participants with zero CAC on the baseline scan, or progressive CAC when the baseline scan demonstrated CAC and there was an increase in CAC ≥50 Agatston units per year. OUTCOMES: Atherosclerotic CVD (myocardial infarction or stroke), congestive heart failure, and all-cause mortality. ANALYTICAL APPROACH: Cause-specific Cox proportional hazards regression, stratified by presence of CAC at baseline. RESULTS: A total of 545 participants without and 765 with prevalent CAC at baseline were included. During a mean 3.3 years between CAC assessments, 177 (32.5%) participants without baseline CAC developed incident CAC while 270 participants (35.3%) with baseline CAC developed a ≥50 Agatston units per year increase in CAC. After multivariable adjustment, incident CAC was associated with 2.42-fold higher rate of atherosclerotic CVD (95% confidence interval [CI]: 1.23-4.79) and 1.82-fold higher rate of all-cause mortality (95% CI: 1.03-3.22). Progressive CAC (≥50 units per year) was not associated with atherosclerotic CVD (hazard ratio [HR]: 1.42; 95% CI: 0.85-2.35) but was associated with a 1.73-fold higher rate of all-cause mortality (95% CI: 1.31-2.28). Progressive CAC was not associated with incident heart failure. LIMITATIONS: Residual confounding and limited statistical power for some outcomes. CONCLUSIONS: Among adults with CKD stages 2-4, CAC progression over a mean 3.3 years was associated with higher risk of atherosclerotic CVD and all-cause mortality. The associations were strongest among participants without CAC at baseline.

Real-Life Experience on the Effect of SGLT2 Inhibitors vs. Finerenone vs. Combination on Albuminuria in Chronic Kidney Disease.

BACKGROUND: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these treatments in real-world experience. The aim of this retrospective study is to report the effects of SGLT2 inhibitors, finerenone, and their combination in CKD patients in our community-based setting. METHODS: Ninety-eight patients with CKD with an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min per 1.73 m2 and a urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g were included. Patients were divided into three groups: two monotherapy groups of SGLT2 inhibitors or finerenone and a third combination group of therapy with SGLT2 inhibitors for the first 4 months and SGLT2 inhibitors and finerenone subsequently. The primary outcomes were the timing and percentage of patients achieving a >50% reduction in UACR from baseline. RESULTS: Group 1 comprised 52 patients on SGLT2i, group 2 had 22 patients on finerenone, and group 3 had 24 patients on combination therapy. The baseline median UACR and mean eGFR were 513 mg/g and 47.9 mL/min per 1.73 m2 in group 1, 548.0 mg/g and 50.5 mL/min per 1.73 m2 in group 2, and 800 mg/g and 60 mL/min per 1.73 m2 in group 3. At baseline, 71 (72.4%) patients were on the angiotensin-converting enzyme inhibitor (ACEi) or the angiotensin receptor blocker (ARB), and 78 (79.5%) patients had type 2 diabetes. After 8 months of follow-up, a >50% decrease in albuminuria was achieved in 96% of patients in group 3, compared to 50% in group 1 and 59% in group 2 (p-values were <0.01 and <0.01, respectively). There was a statistically but not clinically significant change in mean potassium levels in group 2 (+0.4 mmol/L) compared to either group 1 (0.0 mmol/L with p-value: <0.01) or group 3 (-0.01 mmol/L with p-value: <0.01). However, there was no difference in potassium levels when comparing groups 1 and 3. At the end of the follow-up, the average difference in eGFR was -3.4 (8.8), -5.3(10.1), and -7.8 (11.2) mL/min per 1.73 m2 in groups 1, 2, and 3, respectively, without a statistically significant difference between groups. CONCLUSIONS: In this real-world experience in our community setting, the combination of SGLT2 inhibitors and finerenone in our adult patients with CKD was associated with a very significant and clinically relevant reduction in UACR, without an increased risk of hyperkalemia. Combination therapy of SGLT2 inhibitor and finerenone regarding background use of ACEi/ARB is feasible and should be encouraged for further albuminuria reductions in CKD patients.

Kidney Care in Times of Crises: A Review.

The global burden of kidney disease is increasing, paralleled by a rising number of natural and man-made crises. During these tumultuous times, accessing vital health care resources becomes challenging, posing significant risks to individuals, particularly those with kidney disease. This review delves into the impact of crises on kidney disease, with a particular focus on acute kidney injury (AKI), kidney failure, and kidney transplant. Patients experiencing crush injuries leading to AKI may encounter delayed diagnosis due to the chaotic nature of disasters and limited availability of resources. In chronic crises such as conflicts, patients with kidney failure are particularly affected, and deviations from dialysis standards are unfortunately common, impacting morbidity and mortality rates. Additionally, crises also disrupt access to kidney transplants, potentially compromising transplant outcomes. This review underscores the critical importance of preparedness measures and proactive management for kidney disease in crisis settings. Collaborative efforts among government bodies, rescue teams, health care providers, humanitarian agencies, and nongovernmental organizations are imperative to ensure equitable and reasonable care for kidney disease patients during times of crises, with the aim of saving lives and improving outcomes.

[Which octogenarians benefit from the intensive care unit? A proposal for triage]. / Welke tachtigplussers profiteren van intensive care?

Intensive care unit (ICU) treatment can be associated with substantial suffering of patients, and those over eighty years old carry a much worse prognosis than younger ICU patients. Nevertheless, in the Netherlands we admit many people over the age of eighty to the ICU. Is this good practice? Whilst some elderly people may benefit, others don't. ICU treatment without mechanical ventilation is associated with less suffering, can still lead to a good outcome, and thus can often be justified in patients over eighty years. Full ICU treatment including prolonged mechanical ventilation, however, should only be used in selected cases.

Motor learning and performance in schizophrenia and aging: two different patterns of decline.

Psychomotor slowing has consistently been observed in schizophrenia, however research on motor learning in schizophrenia is limited. Additionally, motor learning in schizophrenia has never been compared with the waning of motor learning abilities in the elderly. Therefore, in an extensive study, 30 individuals with schizophrenia, 30 healthy age-matched controls and 30 elderly participants were compared on sensorimotor learning tasks including sequence learning and adaptation (both explicit and implicit), as well as tracking and aiming. This paper presents new findings on an explicit motor sequence learning task, an explicit verbal learning task and a simple aiming task and summarizes all previously published findings of this large investigation. Individuals with schizophrenia and elderly had slower Movement Time (MT)s compared with controls in all tasks, however both groups improved over time. Elderly participants learned slower on tracking and explicit sequence learning while individuals with schizophrenia adapted slower and to a lesser extent to movement perturbations in adaptation tasks and performed less well on cognitive tests including the verbal learning task. Results suggest that motor slowing is present in schizophrenia and the elderly, however both groups show significant but different motor skill learning. Cognitive deficits seem to interfere with motor learning and performance in schizophrenia while task complexity and decreased movement precision interferes with motor learning in the elderly, reflecting different underlying patterns of decline in these conditions. In addition, evidence for motor slowing together with impaired implicit adaptation supports the influence of cerebellum and the cerebello-thalamo-cortical-cerebellar (CTCC) circuits in schizophrenia, important for further understanding the pathophysiology of the disorder.

The Role of Cerebellar Intrinsic Neuronal Excitability, Synaptic Plasticity, and Perineuronal Nets in Eyeblink Conditioning.

Evidence is strong that, in addition to fine motor control, there is an important role for the cerebellum in cognition and emotion. The deep nuclei of the mammalian cerebellum also contain the highest density of perineural nets-mesh-like structures that surround neurons-in the brain, and it appears there may be a connection between these nets and cognitive processes, particularly learning and memory. Here, we review how the cerebellum is involved in eyeblink conditioning-a particularly well-understood form of learning and memory-and focus on the role of perineuronal nets in intrinsic membrane excitability and synaptic plasticity that underlie eyeblink conditioning. We explore the development and role of perineuronal nets and the in vivo and in vitro evidence that manipulations of the perineuronal net in the deep cerebellar nuclei affect eyeblink conditioning. Together, these findings provide evidence of an important role for perineuronal net in learning and memory.

Long-acting second-generation injectable antipsychotics for the maintenance treatment of bipolar disorder: a narrative review.

INTRODUCTION: Non-adherence to medication significantly affects bipolar disorder outcomes. Long-Acting Injectable antipsychotics show promise by ensuring adherence and averting relapses. AREAS COVERED: This narrative review sought to evaluate the efficacy of second-generation injectable antipsychotics in bipolar disorder through searches in Embase, MEDLINE, and PsycInfo for randomized controlled trials and mirror-image studies.Risperidone and aripiprazole Long-Acting Injectables demonstrated effectiveness in preventing mood recurrences compared to placebos in adults with bipolar disorder. They showed superiority in preventing mania/hypomania relapses over placebos but did not appear to significantly outperform active oral controls. Notably, active controls seem to be more effective in preventing depression relapses than Long-Acting Injectables. Mirror-Image studies point toward the reduction of hospitalization rates following LAI initiation. EXPERT OPINION: The available evidence points thus toward the efficacy of LAIs, especially in managing manic episodes and reducing hospitalizations, The current evidence does not however immediately support prioritizing LAIs over oral medications in bipolar disorder treatment. More high-quality studies, especially comparing LAIs directly with active controls, are crucial to gain a comprehensive understanding of their efficacy. These findings highlight the need for further research to guide clinicians in optimizing treatment strategies for bipolar disorder.

Patient Care Technician Staffing and Outcomes Among US Patients Receiving In-Center Hemodialysis.

Importance: Dialysis patient care technicians (PCTs) play a critical role in US in-center hemodialysis (HD) care, but little is known about the association of PCT staffing with patient outcomes at US HD facilities. Objective: To estimate the associations of in-center HD patient outcomes with facility-level PCT staffing. Design, Setting, and Participants: This was a retrospective cohort study, with data analysis performed from March 2023 to January 2024. Data on US patients with end-stage kidney disease and their treatment facilities were obtained from the US Renal Data System. Participants included patients (aged 18-100 years) initiating in-center HD between January 1, 2016, and December 31, 2018, who continued receiving in-center HD for 90 days or more and had data on PCT staffing at their initial treating HD facility. Exposure: Facility-level patient-to-PCT ratios (number of HD patients divided by the number of PCTs reported by the treating facility in the prior year), categorized into quartiles (highest quartile denotes the highest PCT burden). Main Outcomes and Measures: Patient-level outcomes included 1-year patient mortality, hospitalization, and transplantation. Associations of outcomes with quartile of patient-to-PCT ratio were estimated using incidence rate ratios (IRRs) from mixed-effects Poisson regression, with adjustment for patient demographics and clinical and facility factors. Results: A total of 236 126 patients (mean [SD] age, 63.1 [14.4] years; 135 952 [57.6%] male; 65 945 [27.9%] Black; 37 777 [16.0%] Hispanic; 153 637 [65.1%] White; 16 544 [7.0%] other race; 146 107 [61.9%] with diabetes) were included. After full adjustment, the highest vs lowest quartile of facility-level patient-to-PCT ratio was associated with a 7% higher rate of patient mortality (IRR, 1.07; 95% CI, 1.02-1.12), a 5% higher rate of hospitalization (IRR, 1.05; 95% CI, 1.02-1.08), an 8% lower rate of waitlisting (IRR, 0.92; 95% CI, 0.85-0.98), and a 20% lower rate of transplant (IRR, 0.80; 95% CI, 0.71-0.91). The highest vs lowest quartile of patient-to-PCT ratio was also associated with an 8% higher rate of sepsis-related hospitalization (IRR, 1.08; 95% CI, 1.03-1.14) and a 15% higher rate of vascular access-related hospitalization (IRR, 1.15; 95% CI, 1.03-1.28). Conclusions and Relevance: These findings suggest that initiation of treatment in facilities with the highest patient-to-PCT ratios may be associated with worse early mortality, hospitalization, and transplantation outcomes. These results support further investigation of the impact of US PCT staffing on patient safety and quality of US in-center HD care.

The effect of the cultural formulation interview on therapeutic working alliance: a study protocol.

Background: The Cultural Formulation Interview (CFI) is designed to improve understanding of patients' mental health care needs. The lack of empirical evidence on the impact and effectiveness of CFI use in clarifying people's perspectives, experiences, context, and identity, and in preventing cultural misunderstandings between migrant patients and clinicians, inspired this study. The objective is to examine the effect of the CFI on the strength of therapeutic working alliances, and the potential mediating or moderating role of perceived empathy. Materials and methods: A multicenter randomized controlled trial will be conducted, involving migrant patients, their confidants, and clinicians. The CFI will be administered in the intervention group, but not in the control group. Validated questionnaires will be used to assess therapeutic working alliances and perceived empathy. T-tests and linear regression analyses will be conducted to investigate between-group differences and possible mediating or moderating effects. Results: This study will indicate whether or not the CFI strengthens the therapeutic working alliance between patients and clinicians, as moderated and/or mediated by perceived empathy. Discussion: Research on the effect and impact of using the CFI in mental health care for migrant patients is important to clarify whether its use strengthens the therapeutic working alliance with clinicians. This can lead to a reduction in cultural misunderstandings and improve mental health care for migrant patients. The results may also be important for the implementation of the CFI as a standard of care. Ethics and dissemination: This research protocol was tailored to the needs of patients in collaboration with experts by experience. It was approved by the Ethical Review Board of the Tilburg Law School and registered in the Clinical Trials Register under number NCT05788315. Positive results may stimulate further implementation of the CFI in clinical practice, and contribute to improving the impact of the CFI on the therapeutic working alliances.

Patient Care Technician Staffing in US Hemodialysis Facilities: An Ecological Study.

Rationale & Objective: Technicians caring for patients receiving dialysis play a critical, frontline role in the care of patients receiving dialysis in the United States. We sought to provide a comprehensive description and identify correlates of US in-center hemodialysis facility patient care technician staffing patterns. Study Design: This was an ecological study. Setting & Participants: US facilities providing hemodialysis and reporting patient care technician staffing, identified using the US Renal Data System. Exposures: Geography, year, and facility characteristics, including aggregated patient characteristics. Outcomes: The study outcome was facility-reported patient-to-patient care technician ratio. Analytical Approach: We examined patient-to-patient care technician ratios by US state and over time and also estimated the differences in patient-to-patient care technician ratios associated with facility characteristics, using robust regression with adjustment for facility-level covariates. Results: The median patient-to-patient care technician ratio among 6,862 US facilities in 2019 was 9.9 (25th-75th percentiles, 8.2-12.0). Median 2019 patient-to-patient care technician ratios varied substantially by US state and region. There was an overall decline (from 10.6 to 9.9) in median patient-to-patient care technician ratios from 2004 to 2019, whereas the percentage of positions that were unfilled increased (from 2.8% to 3.5%). After adjustment, large dialysis organization status (ß, -0.42; 95% CI, -0.61 to -0.23) and larger facility size (ß, -0.51; 95% CI, -0.68 to -0.33) were associated with lower patient-to-patient care technician ratios. Higher patient-to-registered nurse (ß, 0.80; 95% CI, 0.65-0.94) and patient-to-social worker (ß, 0.53; 95% CI, 0.37-0.70) ratios, presence of licensed vocational nurses or licensed practical nurses at the clinic (ß, 0.83; 95% CI, 0.53-1.12), and location in a poverty area (ß, 0.29; 95% CI, 0.13-0.44) were all associated with higher patient-to-patient care technician ratios. Aggregated patient characteristics of patients treated at the facilities were generally not associated with patient-to-patient care technician ratio after adjustment. Limitations: Limited causal inference and potential shifts in staffing after 2019. Conclusions: US dialysis facilities vary considerably in their patient care technician staffing by geography, over time, and by various facility characteristics. Further investigation of US patient care technician staffing is warranted and could lead to better, more stable dialysis staffing, improved staff and patient satisfaction, and higher quality of care.

In the United States, patient care technicians play an important role in hemodialysis care. Although ongoing staffing shortages and turnover among other hemodialysis care providers have been described, little is known about US patient care technician staffing. Examining national data reported by dialysis facilities, we found variability in patient care technician staffing by geography, over time (with fewer patients per patient care technician in more recent years), and by various facility characteristics. This information can be used to target staff recruitment and retention interventions at facilities where patient care technician staffing may be more challenging.

Patient-centric Comparability Assessment of Biopharmaceuticals.

The comparability assessment of a biological product after implementing a manufacturing process change should involve a risk-based approach. Process changes may occur at any stage of the product lifecycle: early development, clinical manufacture for pivotal trials, or post-approval. The risk of the change to impact product quality varies. The design of the comparability assessment should be adapted accordingly. A working group reviewed and consolidated industry approaches to assess comparability of traditional protein-based biological products during clinical development and post-approval. The insights compiled in this review article encompass topics such as a risk-evaluation strategy, the design of comparability studies, definition of assessment criteria for comparability, holistic evaluation of data, and the regulatory submission strategy. These practices can be leveraged across the industry to help companies in design and execution of comparability assessments, and to inform discussions with global regulators.

Factors Associated With Non-vaccination for Influenza Among Patients With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Vaccination for influenza is strongly recommended for people with chronic kidney disease (CKD) due to their immunocompromised state. Identifying risk factors for not receiving an influenza vaccine (non-vaccination) could inform strategies for improving vaccine uptake in this high-risk population. STUDY DESIGN: Longitudinal observational study. SETTING & PARTICIPANTS: 3,692 Chronic Renal Insufficiency Cohort Study (CRIC) participants. EXPOSURE: Demographic factors, social determinants of health, clinical conditions, and health behaviors. OUTCOME: Influenza non-vaccination, which was assessed based on a receipt of influenza vaccine ascertained during annual clinic visits in a subset of participants who were under nephrology care. ANALYTICAL APPROACH: Mixed-effects Poisson models to estimate adjusted prevalence ratios (APRs). RESULTS: Between 2009 and 2020, the pooled mean vaccine uptake was 72% (mean age, 66 years; 44% female; 44% Black race). In multivariable models, factors significantly associated with influenza non-vaccination were younger age (APR, 2.16 [95% CI, 1.85-2.52] for<50 vs≥75 years), Black race (APR, 1.58 [95% CI, 1.43-1.75] vs White race), lower education (APR, 1.20 [95% CI, 1.04-1.39 for less than high school vs college graduate]), lower annual household income (APR, 1.26 [95% CI, 1.06-1.49] for <$20,000 vs >$100,000), formerly married status (APR, 1.22 [95% CI, 1.09-1.35] vs currently married), and nonemployed status (APR, 1.13 [95% CI, 1.02-1.24] vs employed). In contrast, participants with diabetes (APR, 0.80 [95% CI, 0.73-0.87] vs no diabetes), chronic obstructive pulmonary disease (COPD) (APR, 0.80 [95% CI, 0.70-0.92] vs no COPD), end-stage kidney disease (APR, 0.64 [0.56 to 0.76] vs estimated glomerular filtration rate≥60mL/min/1.73m2), frailty (APR, 0.86 [95% CI, 0.74-0.99] vs no frailty), and ideal physical activity (APR, 0.90 [95% CI, 0.82-0.99] vs. physically inactive) were less likely to have non-vaccination status. LIMITATIONS: Possible residual confounding. CONCLUSIONS: Among adults with CKD receiving nephrology care, younger adults, Black individuals, and those with adverse social determinants of health were more likely to have the influenza non-vaccination status. Strategies are needed to address these disparities and reduce barriers to vaccination. PLAIN-LANGUAGE SUMMARY: Identifying risk factors for not receiving an influenza vaccine ("non-vaccination") in people living with kidney disease, who are at risk of influenza and its complications, could inform strategies for improving vaccine uptake. In this study, we examined whether demographic factors, social determinants of health, and clinical conditions were linked to the status of not receiving an influenza vaccine among people living with kidney disease and receiving nephrology care. We found that younger adults, Black individuals, and those with adverse social determinants of health were more likely to not receive the influenza vaccine. These findings suggest the need for strategies to address these disparities and reduce barriers to vaccination in people living with kidney disease.

Health Disparities in Appalachian and Other Rural Communities.

Rural areas are home to a larger proportion of older adults and populations who age within these locales and suffer disproportionately from health, mental health, and economic disparities compared to their urban counterparts. This article will explore the disparities faced by persons that reside in rural communities across the lifespan. It will briefly discuss what is meant by rural. As a rural region at specific risk, the issues confronting those aging in Appalachia will be examined. Finally, best practices and future directions to combat health disparities among rural residents and elders will be discussed. This includes the Appalachian Gerontology Experiences: Advancing Diversity in Aging Research training program which recruits and trains minority and first-generation undergraduate students in aging and health disparity research.

Prime time for chronic kidney disease.

Chronic kidney disease (CKD) represents a public health burden worldwide and is associated with significant morbidity and mortality. Most patients with CKD are managed by primary care practitioners and this educational series hope to improve knowledge and delivery of care to this high-risk patient population with CKD.

Prevention of Radiographic Progression in Higher-Risk Patients with Rheumatoid Arthritis Using Filgotinib in Phase III Studies: Narrative Review of Post Hoc Analyses.

Filgotinib is an oral preferential Janus kinase 1 inhibitor that demonstrated significant reductions in radiographic progression, with an acceptable tolerability and safety profile, vs placebo in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR; FINCH 1) and vs MTX in MTX-naïve patients with RA (FINCH 3). International treatment guidelines identify multiple poor prognostic factors (PPFs) associated with worse disease outcomes among patients with RA. However, questions remain both about the clinical utility of considering PPFs and about which PPFs should drive treatment decisions. Additionally, the role of radiographic findings in clinical practice continues to be discussed and to evolve. This review examines radiographic results from post hoc analyses of phase 3 trials of filgotinib that examined subgroups with 4 PPFs or with baseline estimated rapid radiographic progression (e-RRP). In MTX groups, there were trends toward greater progression among patients with 4 PPFs or e-RRP, suggesting these subgroups may comprise a higher-risk population. Results show general consistency for the efficacy of filgotinib 200 mg plus MTX vs placebo plus MTX/MTX monotherapy on radiographic assessments, including change from baseline in modified total Sharp score and proportions without radiographic progression, even among MTX-IR or MTX-naïve patients with 4 PPFs or e-RRP who may be at higher risk of bone damage. Multivariate analysis identified multiple factors associated with baseline e-RRP status. This summary of the current understanding of benefits associated with filgotinib on radiographic progression and the relevance of baseline factors to these benefits may help inform treatment decisions for patients facing high risk of radiographic progression.