Uncovering the burden of hidradenitis suppurativa misdiagnosis and underdiagnosis: a machine learning approach.

Hidradenitis suppurativa (HS) is a chronic inflammatory follicular skin condition that is associated with significant psychosocial and economic burden and a diminished quality of life and work productivity. Accurate diagnosis of HS is challenging due to its unknown etiology, which can lead to underdiagnosis or misdiagnosis that results in increased patient and healthcare system burden. We applied machine learning (ML) to a medical and pharmacy claims database using data from 2000 through 2018 to develop a novel model to better understand HS underdiagnosis on a healthcare system level. The primary results demonstrated that high-performing models for predicting HS diagnosis can be constructed using claims data, with an area under the curve (AUC) of 81%-82% observed among the top-performing models. The results of the models developed in this study could be input into the development of an impact of inaction model that determines the cost implications of HS diagnosis and treatment delay to the healthcare system.

Impact of psoriasis disease severity and special area involvement on patient-reported outcomes in the real world: an analysis from the CorEvitas psoriasis registry.

BACKGROUND: The impact of psoriasis in special areas (i.e., scalp, nails, palms, soles, genitals) on patient physical functioning, health-related quality of life (HRQoL), and work abilities has not been fully characterized. We assessed associations between disease severity and special area involvement in psoriasis symptoms, HRQoL, and work/activity impairment. METHODS: Patients with psoriasis from the CorEvitas Psoriasis Registry who initiated systemic treatment between 04/2015-06/2020 were included. Outcomes were change from baseline in psoriasis symptoms, Dermatology Life Quality Index (DLQI), and work/activity impairment at 6 months stratified by baseline disease severity and special area involvement. RESULTS: Among 2620 patients, increasing disease severity was associated with worsening patient-reported outcomes. Patients with (46.0%; N = 1205) versus without (54.0%; N = 1415) psoriasis in special areas reported greater HRQoL and work/activity impairment. Over 6 months, patients with unchanged or worsening disease severity had reduced HRQoL and increased symptom severity; incremental increases in patient HRQoL and decreases in symptom severity were associated with improved disease severity. CONCLUSIONS: Higher disease severity and special area involvement was associated with worse outcomes and impaired work abilities. These data highlight the significant impact that adequate treatment of severe psoriasis and/or special area involvement may have on patient HRQoL and function.

Real-world effectiveness of risankizumab in patients with moderate-to-severe psoriasis using the CorEvitas Psoriasis Registry.

BACKGROUND: Psoriasis, an inflammatory skin disease, is often treated with biologic therapeutics. OBJECTIVE: To determine the real-world treatment effectiveness of risankizumab, an interleukin-23 inhibitor, in the treatment of moderate-to-severe plaque psoriasis. METHODS: A retrospective, observational study was conducted using the CorEvitas Psoriasis Registry for eligible adults with a diagnosis of moderate-to-severe psoriasis and persistent use of risankizumab at 12 (±3) months after initiation. Skin clearance measures and patient-reported outcomes were analyzed for the entire study population and by prior biologic treatment. RESULTS: Among 287 patients with persistent risankizumab use at 1 year, most achieved clear or clear/almost clear skin and reported significant reductions in Dermatology Life Quality Index scores, psoriasis symptoms (fatigue, skin pain, and overall itch), and work and activity impairment. LIMITATIONS: The CorEvitas Psoriasis Registry is not necessarily representative of all adults with psoriasis in the United States and Canada and does not measure patient adherence. CONCLUSION: Patients treated with risankizumab, regardless of prior treatment, achieved high levels of clear and clear/almost clear skin, Dermatology Life Quality Index scores of 0/1, and significant reductions in psoriasis symptoms (fatigue, skin pain, and overall itch) and work and activity impairment 1 year after initiation.

Real-world switching patterns and associated characteristics in patients with psoriasis treated with biologics in the United States.

BACKGROUND: Switching therapies is common for patients with psoriasis. OBJECTIVE: To quantify real-world switching rates and characteristics among patients initiating biologics over 24 months. METHODS: Patients aged ≥18 years with ≥2 confirmed psoriasis diagnoses who initiated a new biologic were identified from a US-payer claims database (Merative® MarketScan®) Switching rates were reported over 24 months using Kaplan-Meier survival analysis, and multivariable Cox regression analyses were performed to identify associated patient characteristics. RESULTS: A total of 7997 patients were included, with overall treatment switch rates at 14.4% at 12 months and 26.0% at 24 months. IL-23 inhibitors were associated with the lowest risk of switching compared with TNF, IL-17, and IL-12/23 inhibitors over 24 months (p < 0.0001). Switch rates varied between specific biologics, with the lowest switch rates observed for patients treated with risankizumab at 8.5% followed by guselkumab at 15.7% over 24 months. Prior targeted immune modulator use, age, and female gender were predictors of switching (adjusted hazard ratio; 1.23, 1.31, and 1.40, respectively; p ≤ 0.0005). LIMITATIONS: Claims data may be subject to data errors and reasons for switching cannot be determined. CONCLUSION: Switching was common in psoriasis patients using biologics over 24 months, with the lowest risk of switching observed with IL-23 inhibitors.

Real-world dose escalation of biologics for moderate-to-severe psoriasis in the United States.

AIM: To compare real-world dose escalation of risankizumab with other US Food and Drug Administration (FDA)-approved biologic treatments for management of moderate-to-severe psoriasis (PsO) in the United States. METHODS: The Merative® MarketScan® Research Database was used to identify adults with ≥2 medical claims for PsO, ≥3 claims of the index biologic medication in the maintenance period, and ≥6 months continuous enrollment pre-induction and ≥6 months after initiation of the maintenance period. Dose escalation was defined as ≥2 dosing intervals where the average daily dose was ≥30% higher than the expected daily dose (per FDA-approved dosing). Comparisons between risankizumab and other cohorts were made using chi-square tests and logistic regression models. RESULTS: At the 30% threshold, the percentage of patients with dose escalation in the full maintenance period was significantly lower with risankizumab (2.0%) compared with other drug classes (tumor necrosis factor, interleukin (IL)-12/23, IL-17, or other IL-23 inhibitors: 17.6%, 10.0%, 18.3%, or 7.1%, respectively; p < 0.0001 for each) and individual biologics (adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab; 17.9%, 10.0%, 15.7%, 18.0%, and 7.2%, respectively; p < 0.0001). CONCLUSION: A significantly lower proportion of risankizumab-treated patients with PsO had dose escalations compared with patients treated with other biologics.

Healthcare Resource Use in Patients with Immune-Mediated Conditions Treated with Targeted Immunomodulators During COVID-19 Pandemic: A Retrospective Claims Analysis.

INTRODUCTION: The impact of the COVID-19 pandemic on routine medical care may result in altered healthcare resource use in patients with immune-mediated conditions. The aim of this study was to determine the impact of treatment interruptions in patients with and without COVID-19 infections who were treated with targeted immunomodulators (TIMs) in the USA. METHODS: Data from the IBM® MarketScan® Research Databases were analyzed in patients with immune-mediated conditions from January 1, 2018, through December 31, 2020. Healthcare resource use (HCRU) including hospitalizations, emergency department (ED) visits, in-person outpatient visits, and respiratory outcomes was assessed in a cohort of patients without COVID-19 who had uninterrupted versus interrupted TIM use. The impact of treatment interruption on HCRU and respiratory outcomes was also evaluated in a cohort of patients with COVID-19. Results from adjusted logistic regression were reported as adjusted odds ratios (aORs) with 95% confidence intervals. RESULTS: Approximately 25% of patients in both the COVID-19 (N = 787) and non-COVID-19 cohorts (N = 77,178) experienced interruptions in TIM therapy. In the non-COVID-19 cohort, the likelihood of being hospitalized was 20% less in patients with uninterrupted versus interrupted TIM use (aOR = 0.80, 95% CI 0.71-0.90). Patients with uninterrupted TIM use had a similar likelihood of an ED visit (aOR = 0.99, 95% CI 0.91-1.08) and respiratory outcome (aOR = 0.97, 95% CI 0.71-1.31) versus patients with interrupted TIM use. The likelihood of having an in-person outpatient visit was 87% greater in patients with uninterrupted versus interrupted TIM use (aOR = 1.87, 95% CI 1.81-1.94). Similar findings were observed in the COVID-19 cohort. CONCLUSION: This analysis of real-world claims data showed that uninterrupted TIM use was not associated with an increased likelihood of hospitalizations, ED visits, or negative respiratory outcomes compared to interrupted TIM use among patients with immune-mediated conditions, regardless of COVID-19 diagnosis.

A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis.

INTRODUCTION: Upadacitinib and tofacitinib are Janus kinase inhibitors approved for moderate-to-severe rheumatoid arthritis (RA). In the absence of head-to-head trials comparing their effectiveness, this study assessed the efficacy of upadacitinib 15 mg once-daily monotherapy/combination therapy against tofacitinib 5 mg twice-daily combination therapy among patients with RA using matching-adjusted indirect comparisons (MAICs). METHODS: The first of two MAICs used individual patient data (IPD) from the 14-week SELECT-MONOTHERAPY trial (upadacitinib [n = 217] vs. methotrexate [n = 216]) and published data from the ORAL Standard trial (tofacitinib + methotrexate [n = 204] vs. methotrexate [n = 108]). The second MAIC used IPD from the 26-week SELECT-COMPARE trial (upadacitinib + methotrexate [n = 647] vs. adalimumab + methotrexate [n = 324]) and published data from ORAL Strategy (tofacitinib + methotrexate [n = 376] vs. adalimumab + methotrexate [n = 386]). Data from patients in the upadacitinib trials were re-weighted based on age, sex, race, swollen joint count 66/28, tender joint count 68/28, C-reactive protein (CRP), and patients' global assessments to match the patient characteristics in tofacitinib trials. After matching, ACR20/50/70 and clinical remission (SDAI[CRP] ≤ 3.3, CDAI ≤ 2.8, DAS28-ESR/CRP < 2.6) were compared for upadacitinib vs. tofacitinib + methotrexate at month 3 and upadacitinib + methotrexate vs. tofacitinib + methotrexate at months 3 and 6 using Wald tests. RESULTS: At month 3, upadacitinib monotherapy patients experienced significantly larger improvement in ACR70 compared to tofacitinib + methotrexate (mean difference in difference [DID]: 9.9%; p = 0.019), while upadacitinib + methotrexate was associated with higher ACR50 compared to tofacitinib + methotrexate (DID: 12.9%; p = 0.011). At month 6, upadacitinib + methotrexate patients experienced significantly larger improvement in SDAI/CDAI/DAS28-ESR clinical remission compared to tofacitinib + methotrexate, with DIDs of 9.1% (p = 0.011), 7.5% (p = 0.038), and 11.3% (p = 0.002), respectively. CONCLUSIONS: Compared to tofacitinib combination therapy, treatment with upadacitinib monotherapy and combination therapy were associated with improved outcomes at 3/6 months (monotherapy: ACR70; combination: ACR50, SDAI, CDAI, and DAS28-ESR remission).

Economic Impact of Non-Medical Switching from Originator Biologics to Biosimilars: A Systematic Literature Review.

INTRODUCTION: A systematic literature review was conducted to review and summarize the economic impact of non-medical switching (NMS) from biologic originators to their biosimilars (i.e., switching a patient's medication for reasons irrelevant to the patient's health). METHODS: English publications reporting healthcare resource utilization (HRU) or costs associated with biosimilar NMS were searched in PubMed and EMBASE over the past 10 years and from selected scientific conferences over the past 3 years, along with gray literature for all biologics with an approved biosimilar (e.g., tumor-necrosis factor inhibitors, erythropoiesis-stimulating agents, insulin and hormone therapies). RESULTS: A total of 1311 publications were retrieved, where 54 studies met the selection criteria. Seventeen studies reported increased real-world HRU or costs related to biosimilar NMS, e.g., higher rates of surgery (11%), steroid use (13%) and biosimilar dose escalating (6-35.4%). Among the studies that the estimated cost impact associated with NMS, 33 reported drug costs reduction, 12 reported healthcare costs post-NMS without a detailed breakdown, and 5 reported NMS setup and managing costs. Cost estimation/simulation studies demonstrated the cost reduction associated with NMS. However, variation across studies was substantial because of heterogeneity in study designs and assumptions (e.g., disease areas, scenarios of drug price discount rates, cost components, population size, study period, etc.). CONCLUSION: Real-world studies reporting the economic impact of biosimilar NMS separately from drug costs are emerging, and those that reported such results found increased HRU in patients with biosimilar NMS. Studies of cost estimation have been largely limited to drug prices. Comprehensive evaluation of the economic impact of NMS should incorporate all important elements of healthcare service needs such as drug price, biologic rebates, HRU, NMS program setup, administration and monitoring costs. FUNDING: AbbVie.

Risk of Developing Additional Immune-Mediated Manifestations: A Retrospective Matched Cohort Study.

INTRODUCTION: Immune-mediated inflammatory diseases (IMIDs) cause significant impairment in quality of life. Although they share similar genetic factors, environmental precipitants, and pathophysiological mechanisms, there is little evidence on the risk of developing subsequent IMIDs after an initial IMID diagnosis. We sought to assess the risk of developing subsequent IMIDs among patients diagnosed with an initial IMID. METHODS: This retrospective matched cohort study used a large US commercial health insurance claims database (01/01/2006-09/30/2015). The risks of developing secondary IMIDs among patients aged 18-64 years with a diagnosis of one of nine IMIDs of interest (ankylosing spondylitis, celiac disease, hidradenitis suppurativa [HS], inflammatory bowel disease, lupus, psoriatic arthritis [PsA], psoriasis, rheumatoid arthritis, and uveitis) as identified from diagnosis codes on medical claims were compared with up to 1000 matched controls without the primary IMID using Cox proportional hazards models. RESULTS: Across the nine IMIDs of interest, there were 398,935 unique case patients matched to 256,795,796 non-unique control patients. Case patients with an initial IMID had higher risks of developing each, any one, and any two of the other eight secondary IMIDs compared to their matched controls. Hazard ratios [95% confidence intervals] for the risk of developing any one secondary IMID ranged from 5.4 [5.0, 5.8] (initial IMID: HS) to 62.2 [59.9, 64.6] (initial IMID: PsA), and hazard ratios for developing any two secondary IMIDs ranged from 3.0 [2.3, 3.8] (HS) to 75.2 [69.3, 81.7] (PsA). CONCLUSIONS: This study demonstrates that the risk of developing a second IMID is significantly higher for individuals who have already experienced a first IMID in a large and contemporary US claims database. Certain pairs of IMIDs co-occur more frequently than others. The risk of developing subsequent IMIDs may be an important consideration for clinicians when selecting treatment strategies. FUNDING: Abbvie.

Systematic review and network meta-analysis: effect of biologics on radiographic progression in rheumatoid arthritis.

AIM: To evaluate the comparative effectiveness of biologics in inhibiting radiographic progression among rheumatoid arthritis (RA) patients. MATERIALS & METHODS: Bayesian network meta-analysis of published trials investigating the USA FDA approved biologics treatment in RA patients, using methotrexate (MTX) as the reference comparator. RESULTS: Nine trials met the inclusion criteria for base case analysis. Compared with MTX, most biologics (except golimumab) + MTX had significantly lower rates of radiographic progression at 1 year. Mean difference in radiographic progression rates between MTX monotherapy and biologics + MTX was highest for adalimumab + MTX (-3.8) and lowest for tocilizumab + MTX (-0.7). Inhibition of radiographic progression was sustained. CONCLUSION: Biologics inhibit radiographic progression in patients with RA at 1 year; however, published evidence beyond 1 year is limited.

Is Patient Support Program Participation Associated with Longer Persistence and Improved Adherence Among New Users of Adalimumab? A Retrospective Cohort Study.

INTRODUCTION: Adalimumab (ADA) is a medication used in the treatment of several autoimmune diseases. Despite the beneficial effects of ADA, its adherence and persistence rates are low. Patients treated with ADA from Clalit Health Services (CHS) can enroll in AbbVie's patient support program (PSP), which aims to improve ADA adherence and persistence. Therefore, we examine whether PSP participation is associated with a longer persistence and/or an improved adherence to ADA. METHODS: A real-world retrospective cohort study of all new ADA users from CHS, comparing those enrolled in the offered PSP to those not enrolled. The data regarding PSP users can be tracked using CHS's data warehouse. The index date was defined as the date of the patients' first purchase of ADA occurring between August 1, 2012 and December 31, 2014. The follow-up data were collected at 12, 24, and 36 months. Persistence was assessed using survival analyses of time until discontinuation, and adherence was assessed using medication possession ratio (MPR). RESULTS: There were 1520 patients in the study, 755 (49.7%) of whom were PSP users. PSP users were 54.3% female vs. 51.9% among non-PSP users (p = 0.355) and they were significantly younger than non-PSP users (mean age 42.3 vs. 45.0 years, p = 0.002) The PSP and non-PSP users' persistence was 673 and 574 days, respectively (p < 0.001). Further, the PSP users were more likely than the non-PSP users to be persistently taking medication at the 12-month follow-up (57.5% vs. 45.6%, p < 0.001). The 12-month mean adherence rate among those with at least 12 months of persistence was significantly improved for the PSP users compared to the non-PSP users (94.1% vs. 92.9%, p = 0.026). CONCLUSION: The AbbVie PSP provided to CHS patients was associated with a longer persistence among new users of ADA. It was also associated with significantly higher adherence rate within the first 12 months. FUNDING: AbbVie Inc.

Similar Improvements in Patient-Reported Outcomes Among Rheumatoid Arthritis Patients Treated with Two Different Doses of Methotrexate in Combination with Adalimumab: Results From the MUSICA Trial.

INTRODUCTION: In patients with rheumatoid arthritis (RA), combination treatment with methotrexate (MTX) and adalimumab is more effective than MTX monotherapy. From the patients' perspective, the impact of reduced MTX doses upon initiating adalimumab is not known. The objective was to evaluate the effects of low and high MTX doses in combination with adalimumab initiation on patient-reported outcomes (PROs), in MTX-inadequate responders (MTX-IR) with moderate-to-severe RA. METHODS: MUSICA was a randomized, double-blind, controlled trial evaluating the efficacy of 7.5 or 20 mg/week MTX, in combination with adalimumab for 24 weeks in MTX-IR RA patients receiving prior MTX ≥ 15 mg/week for ≥ 12 weeks. PROs were recorded at each visit, including physical function, health-related quality-of-life, work productivity, quality-of-sleep, satisfaction with treatment medication, sexual impairment due to RA, patient global assessment of disease activity (PGA), and patient pain. Last observation carried forward was used to account for missing values. RESULTS: At baseline, patients in both MTX dosage groups had similar demographics, disease characteristics, and PRO scores. Overall, initiation of adalimumab led to significant improvements from baseline in the PROs assessed for both MTX dosage groups. Improvements in presenteeism from baseline were strongly correlated with corresponding improvements in SF-36 (vitality), pain, and physical function. Physical and mental well-being had a good correlation with improvement in sleep. Overall, improvements in disease activity from baseline were correlated with improvements in several PROs. CONCLUSIONS: The addition of adalimumab to MTX in MTX-IR patients with moderate-to-severe RA led to improvements in physical function, quality-of-life, work productivity, quality of sleep, satisfaction with treatment medication, and sexual impairment due to RA, regardless of the concomitant MTX dosage. FUNDING: AbbVie. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT01185288.

Clinical and economic analysis of outcomes of dose tapering or withdrawal of tumor necrosis factor-α inhibitors upon achieving stable disease activity in rheumatoid arthritis patients.

OBJECTIVE: To compare the real-world, 5-year clinical and cost impact of maintaining treatment with the tumor necrosis factor-α inhibitors (anti-TNFs) adalimumab, etanercept, or infliximab vs dose tapering or withdrawal in rheumatoid arthritis (RA) patients who have achieved remission (defined as a 28-joint count Disease Activity Score [DAS28] < 2.6) or low disease activity (LDA; DAS28 < 3.2). METHODS: Using a 5-year Markov model with 1-month cycle length, we examined the clinical and cost impact of three treatment strategies: withdrawal, tapering, or maintenance of anti-TNFs among RA patients in remission or who have achieved LDA. This model assessed the time to loss of disease control, time to regaining control after treatment reinitiation, and associated medical and anti-TNF costs. To determine the risk of losing disease control, 14 studies (2309 patients) were meta-analyzed, adjusted for treatment strategy, anti-TNF, RA patient type (early or established RA), and model entry criterion (remission or LDA). RESULTS: Anti-TNF withdrawal and tapering incurred comparable 5-year total costs (€37,900-€59,700 vs €47,500-€59,200), which were lower than those incurred by anti-TNF maintenance (€67,100-€72,100). Established RA patients had higher total costs than early RA patients (€45,900-€72,100 vs €37,900-€71,700). Maintenance was associated with the longest time to loss of disease control (range, 27.3-47.1 months), while withdrawal had the shortest (range, 6.9-30.5 months). CONCLUSION: Dose tapering or withdrawal of anti-TNFs results in similar reduction of health care costs but less time in sustained disease control compared to maintaining therapy. Future research is needed to understand the long-term clinical consequences of these strategies and patient preferences for treatment withdrawal.

Long-Term Effectiveness of Adalimumab in Patients with Rheumatoid Arthritis: An Observational Analysis from the Corrona Rheumatoid Arthritis Registry.

INTRODUCTION: Current recommendations for the management of rheumatoid arthritis (RA) focus on a treat-to-target approach with the objective of maximizing long-term health-related quality-of-life in patients with RA. Published studies from randomized clinical trials have reported limited data regarding the long-term efficacy and safety of adalimumab in patients with RA. This study aims to evaluate the long-term (10+ years) persistency and effectiveness of adalimumab in patients with RA in a real-world setting. METHODS: Included in this study were biologic-naïve adults with RA initiating adalimumab during follow-up enrolled in the Corrona RA registry. More than 10 years of data on persistency of adalimumab and rheumatologist-supplied reasons for discontinuation were examined. Among patients who persisted on adalimumab over the years, clinical [e.g., clinical disease activity index scores (CDAI), physician global assessment, tender joint count, and swollen joint count] and patient-reported outcomes (PRO), such as physical function, pain, fatigue, and morning stiffness, were examined. RESULTS: Of 1791 biologic-naive patients treated with adalimumab who had ≥1 follow-up registry visit, 64.1% were still on therapy at 1 year and 10.2% were still on therapy by the end of year 12. Among patients who persisted on adalimumab for at least 1 year (77.1% female, mean age 53.9 years), 67.0% were in low disease activity (LDA)/remission (CDAI ≤10) and had clinically meaningful improvements from baseline in all clinical assessments and PROs. Initial improvements in LDA/remission and in clinical and PRO assessments observed at year 1 were sustained in those patients who remained on adalimumab over 10 years of follow-up. Among patients who discontinued adalimumab, 61.6% were not in LDA/remission and 41.9% switched to another biologic within 12 months after discontinuing adalimumab. CONCLUSIONS: Real-world data demonstrate a sustained effectiveness of adalimumab in the treatment of RA for patients who remained on therapy for 10 years. FUNDING: Corrona, LLC and AbbVie.

Real-world Effectiveness of Biologic Disease-modifying Antirheumatic Drugs for the Treatment of Rheumatoid Arthritis After Etanercept Discontinuation in the United Kingdom, France, and Germany.

PURPOSE: The purpose of this study was to assess the real-world effectiveness of patients with rheumatoid arthritis (RA) who discontinued etanercept treatment and subsequently received another tumor necrosis factor α (TNF-α) inhibitor or a non-TNF-α biologic in the United Kingdom, France, and Germany. METHODS: Medical record data of patients with RA were collected from a panel of rheumatologists in the United Kingdom, France, and Germany. Patients were required to have a diagnosis of RA, be ≥18 years old, and have initiated use of another TNF-α inhibitor (adalimumab, certolizumab pegol, golimumab, or infliximab) or a non-TNF-α biologic (abatacept or tocilizumab) between January 2014 and May 2015 after discontinuing use of etanercept. Reasons for discontinuing use of etanercept and selecting a second biologic disease-modifying antirheumatic drug (DMARD) were described. Study outcomes included European League Against Rheumatism (EULAR) response and change in Clinical Disease Activity Index (CDAI) score. The study outcomes were compared among treatment groups (ie, TNF-α inhibitors and non-TNF-α biologics) using descriptive and multivariable-adjusted analyses. As a secondary analysis, the study outcomes were also descriptively compared between each of the TNF-α inhibitors. Because adalimumab is one of the most commonly used TNF-α inhibitor to treat RA, a secondary analysis was conducted to compare the outcomes among adalimumab, other TNF-α inhibitors, and non-TNF-α inhibitors. FINDINGS: Patient characteristics before initiating treatment with a second DMARD were similar across treatment groups (all TNF-α inhibitors [n = 296] and non-TNF-α biologics [n = 276]). The most common reasons for discontinuing etanercept treatment were inadequate response, adverse effects, and patient preference. After etanercept, TNF-α inhibitors overall were associated with a significantly lower EULAR good response rate (56.0% vs. 64.4%, P < 0.05) and smaller CDAI score change (-6.3 vs -7.3, P = .06) relative to non-TNF-α biologics. However, the proportion of patients achieving an EULAR good response was numerically higher for adalimumab versus other TNF-α inhibitors (61.1% vs 51.6%, P = 0.11) and comparable versus non-TNF-α biologics (61.1% vs 64.4%, P = 0.52). Adalimumab was also associated with a CDAI score change significantly greater than that of other TNF-α inhibitors (-7.1 vs -5.8, P < 0.05) and comparable to that of non-TNF-α biologics (-7.1 vs -7.3, P = 0.79). The results were consistent in the multivariable-adjusted analysis and secondary analysis. IMPLICATIONS: In this retrospective analysis of patients with RA in the United Kingdom, France, and Germany, after discontinuation of etanercept treatment, TNF-α inhibitors as a class were overall less effective as second biologic DMARDs relative to non-TNF-α biologics; however, adalimumab was more or as effective as other TNF-α inhibitors and non-TNF-α biologics.

Costs of Providing Infusion Therapy for Rheumatoid Arthritis in a Hospital-based Infusion Center Setting.

PURPOSE: Many hospital-based infusion centers treat patients with rheumatoid arthritis (RA) with intravenous biologic agents, yet may have a limited understanding of the overall costs of infusion in this setting. The purposes of this study were to conduct a microcosting analysis from a hospital perspective and to develop a model using an activity-based costing approach for estimating costs associated with the provision of hospital-based infusion services (preparation, administration, and follow-up) in the United States for maintenance treatment of moderate to severe RA. METHODS: A spreadsheet-based model was developed. Inputs included hourly wages, time spent providing care, supply/overhead costs, laboratory testing, infusion center size, and practice pattern information. Base-case values were derived from data from surveys, published studies, standard cost sources, and expert opinion. Costs are presented in year-2017 US dollars. The base case modeled a hospital infusion center serving patients with RA treated with abatacept, tocilizumab, infliximab, or rituximab. FINDINGS: Estimated overall costs of infusions per patient per year were $36,663 (rituximab), $36,821 (tocilizumab), $44,973 (infliximab), and $46,532 (abatacept). Of all therapies, the biologic agents represented the greatest share of overall costs, ranging from 87% to $91% of overall costs per year. Excluding infusion drug costs, labor accounted for 53% to 57% of infusion costs. IMPLICATIONS: Biologic agents represented the highest single cost associated with RA infusion care; however, personnel, supplies, and overhead costs also contributed substantially to overall costs (8%-16%). This model may provide a helpful and adaptable framework for use by hospitals in informing decision making about services offered and their associated financial implications.

Impact of Participation in the Adalimumab (Humira) Patient Support Program on Rheumatoid Arthritis Treatment Course: Results from the PASSION Study.

INTRODUCTION: Patients with rheumatoid arthritis (RA) who are treated with adalimumab (ADA) are offered a proprietary patient support program (PSP, AbbVie Care®). The main objective of this study was to examine the effectiveness of ADA on RA treatment course over time in the context of PSP utilization. METHODS: PASSION was a 78-week post-marketing observational study of RA patients with an insufficient response to ≥1 DMARD newly initiating ADA in routine clinical care that was conducted in Europe, Israel, Mexico, Puerto Rico, and Australia. One prior biologic DMARD was allowed. The primary endpoint was percentage of patients achieving the minimal clinically important difference (MCID; improvement of ≥0.22 compared to baseline) in Health Assessment Questionnaire (HAQ) Disability Index (HAQ-DI) at week 78. Additionally, multiple clinical and patient-reported outcomes (PROs) were evaluated over time. Patients were categorized based on their participation in the PSP: ever (PSP users) vs. never (PSP non-users). Safety events were monitored throughout the study. RESULTS: Overall, 42.8% of PSP users achieved the MCID in HAQ-DI at week 78 (improvement of at least 0.22 compared to baseline). From 1025 enrolled, 48.7% of patients were PSP users while treated with ADA. The percentage of patients achieving MCID in the HAQ-DI was higher in PSP users vs. PSP non-users (48.1 vs. 37.8%) at week 78 (p < 0.001, NRI). Most of the studied clinical outcomes and PROs showed significant improvements (p < 0.05) from baseline to week 78 favoring PSP users over PSP non-users. CONCLUSIONS: In patients with moderate-to-severe RA who initiated ADA, improvements in clinical, functional, and PROs were achieved in real-world settings with significantly greater improvements among PSP users in comparison with PSP non-users. FUNDING: AbbVie. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01383421.

Effectiveness and healthcare costs among stabilised rheumatoid arthritis patients with dose reduction of adalimumab or etanercept in real world.

OBJECTIVES: We assessed the level of maintained effectiveness and associated healthcare costs in stabilised rheumatoid arthritis (RA) patients who reduced doses of adalimumab or etanercept. METHODS: Eligible patients were identified from a U.S. commercial insurance database using the following criteria: adults with ≥2 RA diagnoses; effectively treated on standard dose of adalimumab or etanercept for a 6-month baseline period; and ≥3 months of dose reduction within a 6-month assessment period following the index date (date of the first reduced dose). Effectiveness was estimated using a validated claims-based algorithm. Multivariate regression models were used to assess maintained effectiveness and healthcare costs in the short-term (months 7-12) and long-term (months 13-24) following the index date, while adjusting for baseline characteristics. Cost per patient maintaining effective treatment (CPME) was calculated as the average total healthcare costs divided by the proportion of patients with maintained effectiveness. RESULTS: Both groups (etanercept=375; adalimumab=610) had 70% females and a mean age of 48 years. Adjusted rates of maintained effectiveness for etanercept vs. adalimumab were 57.5% vs. 64.7% (p=0.028) in the short-term and 44.3% vs. 51.9% (p=0.047) in the long-term. Adjusted healthcare costs were similar for etanercept- and adalimumab-treated patients (short-term: $15,043 vs. $15,041; long-term: $31,461 vs. $30,449). The CPME was $2,915 higher with etanercept-treated patients in short-term and $12,349 higher in long-term compared with adalimumab-treated patients. CONCLUSIONS: Among stabilised RA patients who reduced biologic dosing, a greater proportion of adalimumab-treated patients maintained effectiveness than etanercept-treated patients. Adalimumab was associated with a lower total CPME than etanercept.

Impact of Treatment With Biologic Agents on the Use of Mechanical Devices Among Rheumatoid Arthritis Patients in a Large US Patient Registry.

OBJECTIVE: To assess trends and predictors of mechanical devices/aids use by rheumatoid arthritis (RA) patients since the introduction of biologic disease-modifying antirheumatic drugs (DMARDs). METHODS: Sociodemographic characteristics, disease characteristics, and mechanical aid use (assessed using the Health Assessment Questionnaire) were compared among RA patients ages >17 years at diagnosis, enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry during January 2001 to December 2003 and January 2010 to December 2012. Univariate and multivariate logistic regression analyses were used to identify predictors of mechanical aid use among patients in both cohorts. RESULTS: Sociodemographic characteristics were similar between 1,096 patients in the 2001-2003 cohort and 11,140 patients in the 2010-2012 cohort. Disease activity was significantly lower among patients in the 2010-2012 cohort (mean ± SD Clinical Disease Activity Index score 10.1 ± 11.1 versus 17.0 ± 13.8; P < 0.001). A greater proportion of patients in the 2010-2012 cohort received biologic DMARDs (50.7% versus 32.5%; P < 0.001) and fewer were biologic-naive (39.1% versus 61.6%; P < 0.001). Fewer patients in the 2010-2012 cohort used any mechanical devices/aids (31.1% versus 40.8%; P < 0.001). In multivariate analysis, patients in the 2010-2012 cohort and those with a history of biologic agent use were less likely to use devices/aids (odds ratio [OR] 0.77 [95% confidence interval (95% CI) 0.66-0.90] and OR 0.68 [95% CI 0.62-0.75], respectively). Predictors of greater devices/aids usage included older age, female sex, higher disease activity, and less employment. Effect sizes were greatest for disease activity and employment. CONCLUSION: Mechanical devices/aids use among patients with RA was significantly lower during 2010-2012 versus 2001-2003 and among biologic-experienced patients, suggesting reduced disability.