Serum Concentrations of Infliximab and IL-6 for Predicting One-Year Discontinuation of Infliximab Treatment Owing to Secondary Non-response in Patients with Rheumatoid Arthritis.

Secondary non-response to infliximab (IFX) occurs in some patients with rheumatoid arthritis (RA). Although therapeutic drug monitoring (TDM) is a useful tool to optimize IFX therapy, it is unclear whether it can help to identify the risk of secondary non-response. This study aimed to explore the utility of serum levels of IFX or other biomarkers to predict IFX discontinuation owing to secondary non-response. A single-center, retrospective study was conducted using the Kyoto University Rheumatoid Arthritis Management Alliance cohort database between 2011 and 2020. Serum IFX levels were measured using liquid chromatography-tandem mass spectrometry. An electrochemiluminescence assay was used to quantify serum levels of tumor necrosis factor-α and interleukin-6 and detect anti-drug antibodies. Eighty-four out of 310 patients were eligible for this study. The cutoff levels of biomarkers were determined by receiver operating characteristic analysis. IFX persistence was similar between groups stratified using IFX levels, tumor necrosis factor-α levels, interleukin-6 levels, and anti-drug antibodies positivity. The group with lower IFX and higher interleukin-6 levels had the worst therapy persistence (p = 0.017) and the most frequent disease worsening (90.0%, p < 0.001). Evaluating both interleukin-6 and IFX levels, not just IFX alone, enabled us to identify patients at risk of discontinuing IFX treatment. These findings support the utility of measuring IFX and interleukin-6 levels for successful maintenance therapy for RA.

Persistence with Early-Line Abatacept versus Tumor Necrosis Factor-Inhibitors for Rheumatoid Arthritis Complicated by Poor Prognostic Factors.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling and destruction that leads to severe disability. There are no clear guidelines regarding the order of therapies. Gathering data on treatment patterns outside of a clinical trial setting can provide useful context for clinicians. Objectives: To assess real-world treatment persistence in early-line abatacept versus tumor necrosis factor-inhibitors (TNFi) treated patients with RA complicated by poor prognostic factors (including anti-cyclic citrullinated peptide antibodies [ACPA] and rheumatoid factor [RF] seropositivity). Methods: We performed a multi-center retrospective medical record review. Adult patients with RA complicated by poor prognostic factors were treated with either abatacept or TNFis as the first biologic treatment at the clinic. Poor prognostic factors included ACPA+, RF+, increased C-reactive protein levels, elevated erythrocyte sedimentation rate levels, or presence of joint erosions. We report 12-month treatment persistence, time to discontinuation, reasons for discontinuation, and risk of discontinuation between patients on abatacept versus TNFi. Select results among the subgroup of ACPA+ and/or RF+ patients are presented. Results: Data on 265 patients (100 abatacept, 165 TNFis) were collected. At 12 months, 83% of abatacept patients were persistent versus 66.1% of TNFi patients (P=0.003). Median time to discontinuation was 1423 days for abatacept versus 690 days for TNFis (P=0.014). In adjusted analyses, abatacept patients had a lower risk of discontinuing index treatment due to disease progression (0.3 [95% confidence interval (CI): 0.1-0.6], P=0.001). Among the subgroup of ACPA+ and/or RF+ patients (55 abatacept, 108 TNFis), unadjusted 12-month treatment persistence was greater (83.6% versus 64.8%, P=0.012) and median time to discontinuation was longer (961 days versus 581 days, P=0.048) in abatacept versus TNFi patients. Discussion: Patients with RA complicated by poor prognostic factors taking abatacept, including the subgroup of patients with ACPA and RF seropositivity, had statistically significantly higher 12-month treatment persistence and a longer time to discontinuation than patients on TNFis. Conclusions: In a real-world setting, RA patients treated with abatacept were more likely to stay on treatment longer and had a lower risk of discontinuation than patients treated with TNFis.

Patterns and Persistence of Pharmacotherapy for Children and Adolescents with Attention Deficit Hyperactivity Disorder in South Korea

OBJECTIVE: This study aimed to assess treatment persistence in Korean children and adolescents with attention deficit hyperactivity disorder (ADHD) and the factors influencing their adherence to ADHD pharmacotherapy. METHODS: The study included patients between 6 and 18 years of age with ADHD who were taking various formulations of methylphenidate and atomoxetine on June 1, 2014. Patients were dichotomized as “persistent” or “non-persistent”, depending on whether they continued ADHD therapy for 6 months (therapy persistence). We also investigated if the patients were taking the same medication(s) as before and also classified the patients as “medication persistent” or “non-persistent”. Patient' characteristics were correlated with therapy persistence and medication persistence. Multiple logistic regression analyses were performed to assess potential risk factors for treatment persistence. RESULTS: Overall, 3,317 patients were included in the analysis. A majority of patients were taking stimulants (82.0%), 16.2% were taking non-stimulants and 1.8% were taking a combination therapy of stimulants and non-stimulants. After 6 months, 2,290 patients (69.0%) continued to take medication for ADHD with 1,953 patients taking the same medication(s) as 6 months previously. Common positive factors for therapy persistence and medication persistence were identified as younger age, retardation, and developmental delay, and long-acting formulations of methylphenidate as either monotherapy or in a combination therapy may be used. CONCLUSION: ADHD medications were proven to improve academic performance and social skills of children. Collaboration between patients, parents, school staffs, and prescribers is required to improve the persistent use of ADHD medications.

Baseline predictors of persistence to first disease-modifying treatment in multiple sclerosis.

OBJECTIVES: Patients with multiple sclerosis (MS) require lifelong therapy. However, success of disease-modifying therapies is dependent on patients' persistence and adherence to treatment schedules. In the setting of a large multicenter observational study, we aimed at assessing multiple parameters for their predictive power with respect to discontinuation of therapy. MATERIALS AND METHODS: We analyzed 13 parameters to predict discontinuation of interferon beta-1b treatment during a 2-year follow-up period based on data from 395 patients with MS who were treatment-naïve at study onset. Besides clinical characteristics, patient-related psychosocial outcomes were assessed as well. RESULTS: Among patients without clinically relevant fatigue, males showed a higher persistence rate than females (80.3% vs 64.7%). Clinically relevant fatigue scores decreased the persistence rate in men and especially in women (71.4% and 51.2%). Besides gender and fatigue, univariable and multivariable analyses revealed further factors associated with interferon beta-1b therapy discontinuation, namely lower quality of life, depressiveness, and higher relapse rate before therapy initiation, while higher education, living without a partner, and higher age improved persistence. CONCLUSIONS: Patients with higher grades of fatigue and depressiveness are at higher risk to prematurely discontinue MS treatment; especially, women suffering from fatigue have an increased discontinuation rate.

The impact of persistence with therapy on inpatient admissions and emergency room visits in the US among patients with multiple sclerosis.

OBJECTIVE: Disease-modifying therapy (DMT) for multiple sclerosis (MS) can reduce relapses and delay progression; however, poor adherence and persistence with DMT can result in sub-optimal outcomes. The associations between DMT adherence and persistence and inpatient admissions and emergency room (ER) visits were investigated. METHODS: Patients with MS who initiated a DMT in a US administrative claims database were followed for 1 year. Persistence to initiated DMT was measured as the time from DMT initiation to discontinuation (a gap of >60 days without drug 'on hand') or end of 1-year follow-up. Adherence to initiated DMT was measured during the persistent period and was operationalized as the medication possession ratio (MPR). Patients with an MPR <0.80 were considered non-adherent. Claims during the 1-year follow-up period were evaluated for the presence of an all-cause inpatient admission or an ER visit. Adjusted odds ratios (AORs) for inpatient admission or ER visit comparing persistent vs non-persistent and adherent vs non-adherent patients were estimated using logistic regression models adjusted for patient characteristics. RESULTS: The final sample included 16,218 patients. During the 1-year follow-up period, 35.3% of patients discontinued their initiated DMT and 13.9% were not adherent while on therapy. During that same period, 10.0% of patients had an inpatient admission and 24.9% had an ER visit. The likelihoods of inpatient admission and ER visit were significantly decreased in persistent patients (AOR [95% CI] = 0.50 [0.45, 0.56] and 0.65 [0.60, 0.69], respectively) and in adherent patients (AOR [95% CI] = 0.83 [0.71, 0.97] and 0.86 [0.77, 0.95], respectively). CONCLUSIONS: Persistence and adherence with initiated DMT are associated with decreased likelihoods of inpatient admission or ER visit, which may translate to improved clinical outcomes.