The impact of antifibrotic use on long-term clinical outcomes in the pulmonary fibrosis foundation registry.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease (ILD) with a high mortality rate. The antifibrotic medications pirfenidone and nintedanib have been in use since 2014 for this disorder and are associated with improved rate of lung function decline. Less is known about their long-term outcomes outside of the clinical trial context. METHODS: The Pulmonary Fibrosis Foundation Patient Registry was used for this study. Patients with an IPF diagnosis made within a year of enrollment were included. The treated group was defined as patients receiving either pirfenidone or nintedanib for at least 180 days. The untreated group did not have any record of antifibrotic use. Demographic data, comorbidities, serial lung function, hospitalization, and vital status data were collected from the registry database. The primary outcomes were transplant-free survival, time to first respiratory hospitalization, and time to 10% absolute FVC decline. Time-to-event analyses were performed utilizing Cox proportional hazards models and the log-rank test. Model covariates included age, gender, smoking history, baseline lung function, comorbidities, and oxygen use. RESULTS: The registry contained 1212 patients with IPF; ultimately 288 patients met inclusion criteria for the treated group, and 101 patients were designated as untreated. Patients treated with antifibrotics were significantly younger (69.8 vs. 72.6 years, p = 0.008) and less likely to have smoked (61.1% ever smokers vs. 72.3% never smokers, p = 0.04). No significant differences were seen in race, gender, comorbidities, or baseline pulmonary function between groups. The primary outcome of transplant-free survival was not significantly different between the two groups (adjusted HR 0.799, 95% CI 0.534-1.197, p = 0.28). Time to respiratory hospitalization was significantly shorter in the treated group (adjusted HR 2.12, 95% CI 1.05-4.30, p = 0.04). No significant difference in time to pulmonary function decline was seen between groups. CONCLUSIONS: This multicenter study demonstrated 63% of newly diagnosed IPF patients had continuous antifibrotic usage. Antifibrotics were not associated with improved transplant-free survival or pulmonary function change but was associated with an increased hazard of respiratory hospitalization. Future studies should further investigate the role of antifibrotic therapy in clinically important outcomes in real-world patients with IPF and other progressive ILDs.

Household Influenza Transmission and Healthcare Resource Utilization Among Patients Treated with Baloxavir vs Oseltamivir: A United States Outpatient Prospective Survey.

INTRODUCTION: Influenza is a common, seasonal infectious disease with broad medical, economic, and social consequences. Real-world evidence on the effect of influenza treatment on household transmission and healthcare resource utilization is limited in outpatient settings in the USA. This study examined the real-world effectiveness of baloxavir vs oseltamivir in reducing influenza household transmission and healthcare resource utilization. METHODS: This prospective electronic survey on patient-reported outcomes was conducted between October 2022 and May 2023 via CVS Pharmacy in the USA. Adult participants (≥ 18 years old) were eligible if they filled a prescription for baloxavir or oseltamivir at a CVS Pharmacy within 2 days of influenza symptom onset. Participant demographics, household transmission, and all-cause healthcare resource utilization were collected. Transmission and utilization outcomes were assessed using χ2 and Fisher exact tests. RESULTS: Of 87,871 unique patients contacted, 1346 (1.5%) consented. Of 374 eligible patients, 286 (90 baloxavir- and 196 oseltamivir-treated patients) completed the survey and were included in the analysis. Mean age of participants was 45.4 years, 65.6% were female, and 86.7% were White. Lower household transmission was observed with baloxavir compared with oseltamivir therapy (17.8% vs 26.5%; relative risk = 0.67; 95% CI 0.41-1.11). Healthcare resource utilization, particularly emergency department visits (0.0% vs 4.6%), was also numerically lower in the baloxavir-treated group; no hospitalizations were reported in either cohort. CONCLUSIONS: The findings from this real-world study suggest that antiviral treatment of influenza with baloxavir may decrease household transmission and reduce healthcare resource utilization compared with oseltamivir.

Reduced mortality, complications, and economic burden among medicare beneficiaries receiving influenza antivirals.

INTRODUCTION: Antiviral therapy may be underutilized in patients at high risk for increased clinical and economic burden (e.g. older adults). We aimed to examine the benefits associated with antiviral treatment of seasonal influenza among treated and untreated Medicare beneficiaries. METHODS: This retrospective study of Medicare Claims Research Identifiable Files identified patients ≥66 years old with an influenza diagnosis in outpatient setting between October 2016-March 2019 (flu seasons 2016-2018). Index date defined as date of first claim with influenza diagnosis; baseline as the 12 months pre-index. Treated patients received antivirals ≤2 days from index. Untreated patients had no antivirals ≤6 months post-index. Treated/untreated patients were 1:1 propensity score matched. Outcomes (death, all-cause and respiratory-related healthcare resource utilization [HCRU] and costs) were assessed until death or up to 6 months post-index. Descriptive statistics were reported; Kaplan-Meier estimation was used for survival over time. RESULTS: Among 116,901 matched patient pairs, all-cause mortality within 6 months from index diagnosis was 1.6% among treated versus 4.3% among untreated patients. Rates (treated versus untreated) of all-cause inpatient hospitalizations during follow-up were 13.9% versus 22.7% and respiratory-related hospitalizations were 4.2% versus 9.0%. Mean (SD) total all-cause and respiratory-related costs were $9,830 ($18,616.0) and $900 ($4016.4) among the treated, respectively, versus $13,207 ($24,405.1) and $2,024 ($7,623.7) among untreated, respectively. All differences were statistically significant (p < 0.001). CONCLUSIONS: Lack of antiviral treatment is associated with increased mortality, HCRU, and economic burden in older Medicare beneficiaries with seasonal influenza. Future research should investigate whether the choice of antivirals affects influenza burden.

Previous studies have shown that antiviral drugs help prevent flu-related complications and lower healthcare utilization and costs. However, these previous studies have focused on working aged people with existing health problems. Our study looks at how antiviral treatment can lower the health and financial burden caused by the flu in older adults. Using a Medicare claims database from the 2016­2018 flu season, we identified 116,901 matched (treated versus untreated) patient pairs. All-cause mortality within 6 months from the index diagnosis (defined as the first claim with a flu diagnosis) was 1.6% among treated versus 4.3% among untreated patients. Rates (treated versus untreated) of all-cause inpatient hospitalizations during follow-up (defined as 6 months after the index diagnosis date) were 13.9% versus 22.7% and respiratory-related hospitalizations were 4.2% versus 9.0%. Mean total all-cause and respiratory-related costs were $9,830 and $900 among the treated, respectively, versus $13,207 and $2,024 among untreated, respectively. All differences were statistically significant (p < 0.001). This analysis of older adults with the flu found that prompt antiviral treatment is associated with lower rates of mortality and acute complications, reduced hospitalization, and lower healthcare costs. Use of antiviral treatment for patients at high risk of flu, such as older adults, is warranted.

Mechanical ventilation for COVID-19: Outcomes following discharge from inpatient treatment.

Though mechanical ventilation (MV) is used to treat patients with severe coronavirus disease 2019 (COVID-19), little is known about the long-term health implications of this treatment. Our objective was to determine the association between MV for treatment of COVID-19 and likelihood of hospital readmission, all-cause mortality, and reason for readmission. This study was a longitudinal observational design with electronic health record (EHR) data collected between 3/1/2020 and 1/31/2021. Participants included 17,652 patients hospitalized for COVID-19 during this period who were followed through 6/30/2021. The primary outcome was readmission to inpatient care following discharge. Secondary outcomes included all-cause mortality and reason for readmission. Rates of readmission and mortality were compared between ventilated and non-ventilated patients using Cox proportional hazards regression models. Differences in reasons for readmission by MV status were compared using multinomial logistic regression. Patient characteristics and measures of illness severity were balanced between those who were mechanically ventilated and those who were not utilizing 1-to-1 propensity score matching. The sample had a median age of 63 and was 47.1% female. There were 1,131 (6.4%) patients who required MV during their initial hospitalization. Rates (32.1% versus 9.9%) and hazard of readmission were greater for patients requiring MV in the propensity score-matched samples [hazard ratio (95% confidence interval) = 3.34 (2.72-4.10)]. Rates (15.3% versus 3.4%) and hazard [hazard ratio (95% confidence interval) = 3.12 (2.32-4.20)] of all-cause mortality were also associated with MV status. Ventilated patients were more likely to be readmitted for reasons which were classified as COVID-19, infectious diseases, and respiratory diagnoses compared to non-ventilated patients. Mechanical ventilation is a necessary treatment for severely ill patients. However, it may be associated with adverse outcomes including hospital readmission and death. More intense post-discharge monitoring may be warranted to decrease this associational finding.

Association of biological antirheumatic therapy with risk for type 2 diabetes: a retrospective cohort study in incident rheumatoid arthritis.

OBJECTIVE: To explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients with rheumatoid arthritis (RA). STUDY DESIGN, SETTING AND PARTICIPANTS: Five treatment groups were selected from a United States Electronic Medical Records database of 283 756 patients with RA (mean follow-up, 5 years): never received bDMARD (No bDMARD, n=125 337), tumour necrosis factor inhibitors (TNFi, n=34 873), IL-6i (n=1884), T-cell inhibitors (n=5935) and IL-6i+T cell inhibitor abatacept (n=1213). Probability and risk for T2DM were estimated with adjustment for relevant confounders. RESULTS: In the cohort of 169 242 patients with a mean 4.5 years of follow-up and a mean 641 200 person years of follow-up, the adjusted probability of developing T2DM was significantly lower in the IL-6i (probability, 1%; 95% CI 0.6 to 2.0), T-cell inhibitor (probability, 3%; 95% CI 2.3 to 3.3) and IL-6i+T cell inhibitor (probability, 2%; 95% CI 0.1 to 2.9) groups than in the No bDMARD (probability, 5%; 95% CI 4.6 to 4.9) and TNFi (probability, 4%; 95% CI 3.7 to 4.7) groups. Compared with No bDMARD, the IL-6i and IL-6i+T cell inhibitor groups had 37% (95% CI of HR 0.42 to 0.96) and 34% (95% CI of HR 0.46 to 0.93) significantly lower risk for T2DM, respectively; there was no significant difference in risk in the TNFi (HR 0.99; 95% CI 0.93 to 1.06) and T-cell inhibitor (HR 0.96; 95% CI 0.82 to 1.12) groups. CONCLUSIONS: Treatment with IL-6i, with or without T-cell inhibitors, was associated with reduced risk for T2DM compared with TNFi or No bDMARDs; a less pronounced association was observed for the T-cell inhibitor abatacept.

Comparative Efficacy (DAS28 Remission) of Targeted Immune Modulators for Rheumatoid Arthritis: A Network Meta-Analysis.

INTRODUCTION: The objective of this study was to evaluate the relative efficacy of targeted immune modulators (TIMs) in TIM-naïve/mixed populations (≤ 20% TIM-experienced) and TIM-experienced (> 20% TIM-experienced) adults with moderate-to-severe rheumatoid arthritis with an inadequate response to or intolerance of conventional disease-modifying antirheumatic drugs (cDMARDs). METHODS: A fixed-effects Bayesian network meta-analysis (NMA) was performed using published study-level data from 41 randomized controlled trials (RCTs) identified from two recent systematic literature reviews conducted by the Institute for Clinical and Economic Review, and two additional phase III trials for filgotinib (FINCH-1, FINCH-2). RCTs that compared TIMs with each other, cDMARD therapy, or placebo were included. Treatments included Janus kinase (JAK) inhibitors, tumor necrosis factor α inhibitors (TNFi), and other non-TNFi therapies. Efficacy was defined as achieving remission with a DAS28 score < 2.6 at 12 and 24 weeks. RESULTS: In the 12-week analysis for the TIM-naïve/mixed population, all TIMs combined with cDMARD therapy were significantly more likely to achieve remission compared with a cDMARD alone, with intravenous tocilizumab showing a substantially greater magnitude of effect (odds ratio 19.36; 95% credible interval 11.01-38.16). Similarly, in the 24-week analysis, intravenous and subcutaneous tocilizumab showed the highest odds ratio of achieving DAS28 remission compared with cDMARD therapy. Similar trends were observed for the analyses on monotherapy or TIM-experienced population. CONCLUSIONS: This NMA demonstrated that tocilizumab is associated with a greater likelihood of remission (DAS28 < 2.6) at 12 and 24 weeks compared with most other TIMs, including new JAK inhibitors, when used in combination with a cDMARD or as monotherapy among TIM-naïve/mixed or TIM-experienced populations.

Treatment patterns in US patients hospitalized with COVID-19 and pulmonary involvement.

This study describes the baseline characteristics and treatment patterns of US patients hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) and pulmonary involvement. Patients hospitalized with pulmonary involvement due to COVID-19 (first hospitalization) were identified in the IBM Explorys® electronic health records database. Demographics, baseline clinical characteristics, and in-hospital medications were assessed. For evaluation of in-hospital medications, results were stratified by race, geographic region, age, and month of admission. Of 6564 hospitalized patients with COVID-19-related pulmonary involvement, 50.4% were male, and mean (SD) age was 62.6 (16.4) years; 75.2% and 23.6% of patients were from the South and Midwest, respectively, and 50.2% of patients were African American. Compared with African American patients, a numerically higher proportion of White patients received dexamethasone (19.7% vs. 31.8%, respectively), nonsteroidal anti-inflammatory drugs (NSAIDs; 27.1% vs. 34.9%), bronchodilators (19.8% vs. 29.5%), and remdesivir (9.3% vs. 21.0%). Numerically higher proportions of White patients than African American patients received select medications in the South but not in the Midwest. Compared with patients in the South, a numerically higher proportion of patients in the Midwest received dexamethasone (20.1% vs. 34.5%, respectively), NSAIDs (19.6% vs. 55.7%), bronchodilators (15.9% vs. 41.3%), and remdesivir (10.6% vs. 23.1%). Inpatient use of hydroxychloroquine decreased over time, whereas the use of dexamethasone and remdesivir increased over time. Among US patients predominantly from the South and Midwest hospitalized with COVID-19 and pulmonary involvement, differences were seen in medication use between different races, geographic regions, and months of hospitalization.

Durability of Response to Tocilizumab Therapy in Rheumatoid Arthritis: Data from the US-Based Corrona Rheumatoid Arthritis Registry.

INTRODUCTION: Understanding the durability of response to treatment and factors associated with failure to maintain response in a real-world setting can inform treatment decisions for patients with rheumatoid arthritis (RA). The aim of this study was to analyze durability of response to tocilizumab (TCZ) and factors associated with durability among US patients with RA in routine clinical practice. METHODS: TCZ initiators in the Corrona RA Registry were included. Durability of response was defined as maintaining continuous TCZ treatment and either an improvement of at least minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) score or low disease activity (LDA). Secondary analyses included patients treated with intravenous (IV) TCZ and excluded those who discontinued TCZ without reporting reasons for discontinuation. Durability was calculated with Kaplan-Meier survival analysis. Cox proportional hazards modeling identified factors associated with durability. RESULTS: Among 1789 TCZ initiators, 466, 272, and 162 were persistent (with or without durable response) with follow-up visits at 1, 2, and 3 years, respectively. Median MCID durability of response in CDAI was > 50% after 36 months overall, 26 months for TCZ-IV, and > 50% after 36 months for those with known reasons for discontinuation; longer durability was associated with increased duration of RA and higher baseline CDAI score and shorter durability with history of malignancy and history of diabetes. Median LDA durability of response was 13.0 months overall, for TCZ-IV, and for those with known reasons for discontinuation; shorter durability was associated with history of malignancy, history of diabetes, and higher baseline CDAI score. CONCLUSIONS: Median durability of response to TCZ in RA was > 3 years when defined as maintenance of MCID in CDAI score and > 1 year with the more stringent criteria of maintenance of LDA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01402661.

Clinical outcomes of patients with giant cell arteritis treated with tocilizumab in real-world clinical practice: decreased incidence of new visual manifestations.

BACKGROUND: Placebo-controlled clinical trials have demonstrated the efficacy of tocilizumab (TCZ) for remission maintenance and glucocorticoid sparing in patients with giant cell arteritis (GCA). However, limited data exist on the effectiveness and safety of TCZ for GCA in real-world clinical practice. METHODS: This was a retrospective, single-center analysis of patients with GCA treated with intravenous or subcutaneous TCZ (2010-2018). Outcomes evaluated before and after TCZ initiation included occurrence of flare, time to flare, annualized flare rate, flare characteristics (i.e., polymyalgia rheumatica [PMR] symptoms, cranial manifestations), prednisone use, and safety. Flare was defined as the recurrence of unequivocal GCA manifestations requiring treatment intensification. Subgroup analyses of patients with PMR or visual manifestations at GCA diagnosis were performed. RESULTS: Sixty patients with GCA were included. The median (IQR) disease duration before and after the start of TCZ was 0.6 (0.2-1.6) and 0.5 (0.3-1.4) years, respectively. At least 1 flare was observed in 43 patients (71.7%) before and in 18 (30.0%) after TCZ initiation. Median (IQR) time to flare was 0.5 (0.3-0.7) years before TCZ treatment and 2.1 (0.6-2.6) years after TCZ initiation (HR 0.22; 95% CI 0.10-0.50; p = 0.0003). The annualized flare rate significantly decreased following TCZ use (before TCZ 1.4 [95% CI 1.0-2.1]; after TCZ 0.6 [95% CI 0.3-1.0] events/year; p < 0.001). Similar improvements were observed in patients with visual manifestations or PMR symptoms at GCA diagnosis. TCZ reduced the incidence of new visual manifestations, and no flares associated with permanent vision loss occurred while patients were receiving TCZ. Mean (SD) prednisone dose at TCZ onset and at the end of follow-up was 30 (18.3) and 5 (6.9) mg/day, respectively (p < 0.0001). After TCZ initiation, 46.6% of patients successfully discontinued prednisone. The incidence of adverse events, primarily attributed to glucocorticoids, was similar before and after TCZ initiation. CONCLUSIONS: In this real-world setting, TCZ improved GCA clinical outcomes significantly and demonstrated effectiveness in the subgroups of patients with PMR symptoms and GCA-related visual manifestations at GCA diagnosis. No new cases of blindness occurred after TCZ initiation. Adverse events, many attributable to glucocorticoids, were comparable before and after TCZ treatment.

Baseline Demographics and Clinical Characteristics Among 3471 US Patients Hospitalized with COVID-19 and Pulmonary Involvement: A Retrospective Study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can present as a range of symptoms, from mild to critical; lower pulmonary involvement, including pneumonia, is often associated with severe and critical cases. Understanding the baseline characteristics of patients hospitalized with COVID-19 illness is essential for effectively targeting clinical care and allocating resources. This study aimed to describe baseline demographics and clinical characteristics of US patients hospitalized with COVID-19 and pulmonary involvement. METHODS: US patients with COVID-19 and pulmonary involvement during an inpatient admission from December 1, 2019, to May 20, 2020, were identified using the IBM Explorys® electronic health records database. Baseline (up to 12 months prior to first COVID-19 hospitalization) demographics and clinical characteristics and preadmission (14 days to 1 day prior to admission) pulmonary diagnoses were assessed. Patients were stratified by sex, age, race, and geographic region. RESULTS: Overall, 3471 US patients hospitalized with COVID-19 and pulmonary involvement were included. The mean (SD) age was 63.5 (16.3) years; 51.2% of patients were female, 55.0% African American, 81.6% from the South, and 16.8% from the Midwest. The most common comorbidities included hypertension (27.7%), diabetes (17.3%), hyperlipidemia (16.3%), and obesity (9.7%). Cough (27.3%) and dyspnea (15.2%) were the most common preadmission pulmonary symptoms. African American patients were younger (mean [SD], 62.5 [15.4] vs. 67.8 [6.2]) with higher mean (SD) body mass index (33.66 [9.46] vs. 30.42 [7.86]) and prevalence of diabetes (19.8% vs. 16.7%) and lower prevalence of chronic obstructive pulmonary disease (5.6% vs. 8.2%) and smoking/tobacco use (28.1% vs. 37.2%) than White patients. CONCLUSIONS: Among US patients primarily from the South and Midwest hospitalized with COVID-19 and pulmonary involvement, the most common comorbidities were hypertension, diabetes, hyperlipidemia, and obesity. Differences observed between African American and White patients should be considered in the context of the complex factors underlying racial disparities in COVID-19.

Real-World Persistence with Tocilizumab Compared to Other Subcutaneous Biologic Disease-Modifying Antirheumatic Drugs Among Patients with Rheumatoid Arthritis Switching from Another Biologic.

INTRODUCTION: In patients with rheumatoid arthritis (RA) who have an inadequate response to or intolerance of their first biologic disease-modifying antirheumatic drug (bDMARD), guidelines recommend switching to a different biologic class. The objective of this study was to compare persistence with subcutaneous (SC) tocilizumab to persistence with other SC bDMARDs when these drugs are used as subsequent-line therapy in RA patients who previously received ≥ 1 bDMARD. METHODS: RA patients in a US administrative claims database who initiated a second- or subsequent-line SC bDMARD between January 1, 2012 and June 30, 2017 (initiation date = index date) were included. Persistence was defined as the number of days between the bDMARD initiation date and (1) the last supplied day of medication fill (primary) or (2) the day on which the patient switched or there was a gap in treatment of > 90 days (secondary). Parametric survival models utilizing an exponential distribution with a robust variance estimator were used to compare persistence with tocilizumab to persistence with other bDMARDs. RESULTS: A total of 10,301 patients with 12,704 bDMARD episodes were included. Patients receiving tocilizumab had a significantly higher adjusted median (95% CI) number of days of primary persistence [333 (311-356)] than those receiving adalimumab [280 (268-293); P < 0.001], certolizumab [262 (241-284); P < 0.001], and etanercept [289 (274-304); P = 0.001], and a similar persistence to those receiving abatacept [320 (305-335); P = 0.327] and golimumab [304 (274-333); P = 0.122]. CONCLUSION: Among patients with RA who had previously received ≥ 1 bDMARD, tocilizumab-treated patients exhibited a similar or significantly better biologic persistence than those receiving other bDMARDs.

Methotrexate Discontinuation and Dose Decreases After Therapy With Tocilizumab: Results From the Corrona Rheumatoid Arthritis Registry.

INTRODUCTION: Similar outcomes have been observed between patients with rheumatoid arthritis (RA) responding to tocilizumab (TCZ) with methotrexate (MTX) who discontinued vs. continued MTX and between patients receiving MTX who added TCZ vs. switched to TCZ monotherapy. This study examined MTX discontinuation and dose decreases in patients with RA initiating TCZ in a real-world setting. METHODS: TCZ-naïve patients enrolled in the Corrona RA registry who initiated TCZ in combination with MTX and had a 6-month follow-up visit without TCZ discontinuation were included. Patients were grouped by MTX dose at the time of TCZ initiation (≤ 10 mg, > 10 to ≤ 15 mg, > 15 to ≤ 20 mg, > 20 mg). The primary outcome was the proportion of patients with changes in MTX use at 6 months, with a secondary analysis at 12 months. Changes in disease activity [Clinical Disease Activity Index (CDAI)] and patient-reported outcomes (PROs) at 6 and 12 months were summarized descriptively. RESULTS: Of 444 included patients, 82.7% were female and 83.7% white, with mean (SD) disease duration of 11.6 (9.3) years, baseline CDAI score of 24.0 (15.4), and baseline MTX dose of 17.7 (5.8) mg. At 6 months, 139 patients (31.3%) discontinued or decreased their MTX dose. All MTX dose groups and patients who discontinued, decreased, maintained, or increased their MTX dose displayed improvements in CDAI scores and PROs at 6 months. Similar patterns and results were observed at 12 months. CONCLUSIONS: A considerable proportion of patients initiating TCZ discontinued or decreased their MTX dose after TCZ initiation. Improvements in disease activity and functionality were observed in patients who decreased or stopped MTX. This real-world study confirmed prior observations that discontinuing or decreasing MTX may be a treatment strategy for patients initiating TCZ combination therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01402661.

Rheumatoid arthritis (RA) is a long-term disease that causes joint swelling, stiffness, and pain. Unless RA is treated quickly, patients can experience joint damage and disability. Patients with RA often take methotrexate (MTX) as their first treatment, but many patients do not have sufficient improvement with MTX alone. For these patients, doctors often add another medicine called a biologic to their existing treatment. However, taking more medications is associated with toxic effects and can make it harder for patients to stay on their therapy.Tocilizumab (TCZ) is a biologic that is used to treat RA. In one clinical trial, reported by Kremer et al., patients whose RA improved when they were taking TCZ plus MTX were subsequently able to stop taking MTX and their RA remained well controlled (Arthritis Rheumatol 70(8):1200­1218, 2018). However, researchers had not looked at whether patients outside of a clinical trial (in the "real world") can stop taking MTX or take less MTX after they start taking TCZ. This study used real-world data to examine if patients who start taking TCZ subsequently stop taking or take less MTX.This study showed that many patients were able to stop taking or take less MTX during the year after they started taking TCZ. Patients who stopped or decreased their MTX dose had less-active RA and reported that they felt better and had fewer symptoms. These results suggest that it is common for patients in the real world to stop taking or take less MTX after they start taking TCZ.

Effectiveness of Tocilizumab in Patients with Rheumatoid Arthritis Is Unaffected by Comorbidity Burden or Obesity: Data from a US Registry.

OBJECTIVE: Comorbidity burden and obesity may affect treatment response in patients with rheumatoid arthritis (RA). Few real-world studies have evaluated the effect of comorbidity burden or obesity on the effectiveness of tocilizumab (TCZ). This study evaluated TCZ effectiveness in treating RA patients with high versus low comorbidity burden and obesity versus nonobesity in US clinical practice. METHODS: Patients in the Corrona RA registry who initiated TCZ were stratified by low or high comorbidity burden using a modified Charlson Comorbidity Index (mCCI) and by obese or nonobese status using body mass index (BMI). Improvements in disease activity and functionality after TCZ initiation were compared for the above strata of patients at 6 and 12 months after adjusting for statistically significant differences in baseline characteristics. RESULTS: We identified patients with high (mCCI ≥ 2; n = 195) and low (mCCI < 2; n = 575) comorbidity burden and patients categorized as obese (BMI ≥ 30; n = 356) and nonobese (BMI < 30; n = 449) who were treated with TCZ. Most patients (> 95%) were biologic experienced and about one-third of patients received TCZ as monotherapy, with no significant differences between patients by comorbidity burden or obesity status. Improvement in disease activity and functionality at 6 and 12 months was similar between groups, regardless of comorbidity burden or obesity status. CONCLUSION: In this real-world analysis, TCZ was frequently used to treat patients with high comorbidity burden or obesity. Effectiveness of TCZ did not differ by comorbidity or obesity status.

Comparative Cost per Response for 4 Clinical Endpoints with Tocilizumab Monotherapy vs Adalimumab Monotherapy in a Head-to-Head Randomized Double-Blind Superiority Trial (ADACTA) in Patients with Rheumatoid Arthritis.

INTRODUCTION: The cost-effectiveness of different biologic therapies can be an important component in guiding treatment decisions for patients with rheumatoid arthritis (RA). The objective of this study was to compare drug and adverse event costs and cost per successful clinical response with tocilizumab (TCZ) monotherapy vs adalimumab (ADA) monotherapy in patients with RA in a phase 4 clinical trial. METHODS: Patients received either TCZ intravenously every 4 weeks or ADA subcutaneously every 2 weeks for 24 weeks. Drug and administration costs were based on wholesale acquisition costs and the Centers for Medicare and Medicaid, respectively. Outcomes included patient-level drug costs, cost of hospitalization due to adverse events, and cost per response. Cost per response was calculated by dividing the mean drug plus administration cost by the proportion of patients achieving Disease Activity Score in 28 joints (DAS28) < 2.6 (remission) or 20%, 50%, or 70% improvement in response per the American College of Rheumatology (ACR20/50/70). Hospitalization costs were calculated using the daily hospital cost and number of hospital days. RESULTS: Among the 163 patients treated with TCZ and 162 patients treated with ADA, mean total drug and administration costs per patient over 24 weeks were $18,290.60 and $25,623.10, respectively. Mean drug and administration costs per each clinical response achieved were lower with TCZ than with ADA (DAS28 < 2.6: $45,868 vs $244,174; ACR20: $28,127 vs $51,887; ACR50: $38,720 vs $92,244; ACR70: $56,253 vs $143,136). The total hospital days were 32 days with TCZ and 43 days with ADA; mean hospital costs per patient were $484.50 with TCZ and $651.10 with ADA. CONCLUSION: In this comparative assessment, the cost to achieve all 4 clinical endpoints was lower for patients receiving TCZ than for those receiving ADA.

Risk of Potential Glucocorticoid-Related Adverse Events in Patients with Giant Cell Arteritis: Results from a USA-Based Electronic Health Records Database.

INTRODUCTION: Oral glucocorticoids (GC) have been the mainstay of treatment for giant cell arteritis (GCA). We estimated the risk and dose-effect relationship of potential GC-related adverse events (AEs) in patients with GCA. METHODS: This retrospective, observational cohort study utilized data from the IBM Explorys Electronic Health Records database from 2008 through 2016. Inclusion criteria included the presence of at least two GCA diagnostic codes in subjects aged 50 or older along with supporting laboratory [C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)], prescription data on oral GCs, and at least 12 months of follow-up before and after the first oral GC prescription for GCA (index date). Potential AEs captured on the basis of new diagnoses, prescriptions, and laboratory tests were assessed during the 12 months post-index date. Results were descriptively summarized across cohorts according to quartiles (Q) of mean daily GC dose measured over the first 6 months of follow-up (Q1, ≥ 1.00 to ≤ 13.75 mg; Q2, > 13.75 to ≤ 25.00 mg; Q3, > 25.00 to ≤ 40.00 mg; Q4, > 40.00 mg). RESULTS: We identified 785 eligible patients with GCA. The mean (SD) age of the cohort was 76 (9) years and 70% were female. The mean oral GC dose during the first 6 months post-index was 28.9 mg/day. A dose-effect response was observed from Q1 to Q4 in the following potential GC-related AEs: newly diagnosed type 2 diabetes/HbA1c > 7.5% (range 7.5-24.5%), blood glucose ≥ 200 mg/dL (range 7.5-15%), serious infection (range 16.8-24.8%), cataracts (range 12.0-21.7%), gastrointestinal bleed/ulcer (range 6.0-11.8%), and increase in BMI ≥ 5 units (range 4.1-6.4). CONCLUSIONS: In patients with GCA, potential GC-related AEs increased with higher daily oral GC doses. This highlights the need for effective therapies that reduce GC exposure and toxicity. FUNDING: Genentech, Inc.

Patterns of Prednisone Use in Patients with Rheumatoid Arthritis Initiating Treatment with Tocilizumab in Routine US Clinical Practice.

INTRODUCTION: Prednisone is frequently administered in combination with other therapies for the treatment of rheumatoid arthritis (RA); however, its chronic use is associated with an increased risk of comorbidities and mortality. The objective of this analysis was to evaluate changes in prednisone use among patients with RA treated with tocilizumab (TCZ) in routine US clinical practice. METHODS: TCZ-naïve patients in the Corrona RA registry who initiated TCZ were included. The primary outcome was the proportion of patients with changes in prednisone use over 12 months (primary analysis) and 6 months (secondary analysis). Changes in disease activity over 6 and 12 months (± 3 months) were assessed using the Clinical Disease Activity Index (CDAI). Outcomes were assessed in the overall population and separately for patients receiving TCZ monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs. RESULTS: Of patients receiving prednisone at baseline (mean [SD] dose: 7.7 [5.2] mg/day), 30.6% discontinued prednisone over 12 months; among patients receiving > 7.5 mg of prednisone at the time of TCZ initiation, 63.0% discontinued prednisone or decreased their dose by ≥ 5 mg over 12 months. In secondary analyses, 29.7% of patients receiving prednisone at baseline had discontinued prednisone over 6 months; among those receiving > 7.5 mg of prednisone at baseline, 51.3% discontinued or decreased their dose by ≥ 5 mg over 6 months. Changes in prednisone use and improvement from baseline in CDAI score over 6 and 12 months were comparable between patients who initiated TCZ monotherapy vs. TCZ combination therapy. CONCLUSIONS: In this real-world analysis, many patients initiating TCZ monotherapy or combination therapy were able to discontinue or decrease their prednisone dose over 12 months. Similar changes in prednisone dose were observed over 6 months. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01402661. FUNDING: Corrona, LLC and Genentech, Inc. Plain language summary available for this article.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint damage and disability. The steroid prednisone is a fast-acting and effective treatment for RA and is often prescribed alongside disease-modifying antirheumatic drugs (DMARDs). The health risks associated with the long-term use of prednisone have led to recommendations to minimize prednisone dose and duration of treatment. Few studies have examined the extent to which biologic DMARDs allow rheumatologists to reduce or discontinue the use of prednisone. The objective of this study was to evaluate changes in prednisone dose while receiving tocilizumab (TCZ) in patients with RA seen in routine US clinical practice. Patients who were enrolled in the Corrona RA registry and were beginning treatment with TCZ were included. Changes in prednisone use were evaluated 12 months after starting treatment. Of patients receiving prednisone at study initiation, 30.6% had discontinued prednisone over 12 months; among patients receiving > 7.5 mg of prednisone at the time of TCZ initiation, 63.0% discontinued prednisone or decreased the dose by ≥ 5 mg over 12 months. In secondary analyses, 29.7% of patients receiving prednisone at study initiation had discontinued prednisone over 6 months; among those receiving > 7.5 mg of prednisone at baseline, 51.3% discontinued or decreased the dose by ≥ 5 mg over 6 months. Changes in prednisone use and improvement in disease activity over 6 and 12 months were comparable between patients who initiated TCZ monotherapy or combination therapy with other DMARDs.

Adverse Events in Giant Cell Arteritis and Rheumatoid Arthritis Patient Populations: Analyses of Tocilizumab Clinical Trials and Claims Data.

INTRODUCTION: The safety profile of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) is well established. TCZ was approved to treat giant cell arteritis (GCA) in 2017 in the USA and Europe, and its safety profile in patients with GCA continues to be defined. The objective of this analysis was to examine incidence rates (IRs) of adverse events of special interest (AESI) occurring during the TCZ clinical development program and in healthcare claims data in patients with GCA or RA. METHODS: TCZ-naïve patients with GCA or RA were identified in the MarketScan administrative healthcare claims database. TCZ-treated patients with GCA from the GiACTA trial and TCZ-treated patients with RA from pooled clinical trial data were analyzed. The IRs of AESI (AESI IRs) were calculated for all cohorts. In the claims cohorts, risks of AESI were estimated using Poisson regression. RESULTS: TCZ-naïve claims cohorts comprised 4804 patients with GCA [mean (standard deviation) age 73.4 (9.8) years; follow-up 3.9 (3.1) years] and 15,164 patients with RA [age 60.3 (8.2) years; follow-up, 4.5 (2.8) years]. TCZ-treated clinical trial cohorts comprised 149 patients with GCA [age 69.5 (8.4) years; exposure approx. 138 patient-years (PY)] and 7647 with RA [age 52 (12.6) years; exposure approx. 22,394 PY]. The IRs of infections, stroke, malignancies, myocardial infarction, and gastrointestinal perforations in the GCA claims cohort exceeded those in the RA claims cohort; the risk of AESI (adjusted for age and glucocorticoid use) was higher in patients with GCA than in those with RA. Similar patterns to the claims cohorts in terms of the AESI IRs were observed in clinical trial cohorts, although the number of events was limited in the GCA trial cohort. CONCLUSION: Higher IRs of AESI were observed in patients with GCA versus those with RA in both TCZ-naïve and -treated cohorts. Differences in underlying disease, age, and glucocorticoid use may influence AESI incidence, irrespective of intervention. FUNDING: This study was funded by F. Hoffmann-La Roche Ltd and Genentech, Inc. Article processing charges were funded by F. Hoffmann-La Roche Ltd. Plain language summary is available for this article.

Healthcare Costs of Potential Glucocorticoid-Associated Adverse Events in Patients with Giant Cell Arteritis.

OBJECTIVE: To quantify the healthcare expenditures associated with potential oral glucocorticoid (OGC)-related adverse events (AEs) in patients with giant cell arteritis (GCA). METHODS: Patients with GCA and ≥ 1 OGC prescription fill between 2009 and 2014 were identified from the MarketScan Commercial and Medicare Supplemental claims databases. Patients were stratified into four groups based on cumulative OGC dose (> 0 to ≤ 2607 mg, > 2607 to ≤ 4800 mg, > 4800 to ≤ 7200 mg, and > 7200 mg) during the 1-year follow-up period; incidence of potential AEs and AE-related direct healthcare costs in USD were assessed. Association between the log of cumulative OGC dose and AE-related direct healthcare costs was evaluated, adjusting for baseline characteristics. RESULTS: Of 1602 patients with GCA included, 69% were women; the mean age was 73 years. The mean cumulative OGC dose was 5806 mg during the 1-year follow-up; most exposure occurred in the first 6 months. The proportion of patients with potential OGC-related AEs was 36.5% overall and increased as cumulative dose increased (30.7%-45.3% across dose groups). Unadjusted mean AE-related costs for patients with an AE was USD $12,818. In the multivariable model including all patients, increasing OGC dose was associated with increasing AE-related healthcare costs (cost ratio, 1.38 [95% CI, 1.16-1.64] per 1-unit increase in log of cumulative OGC dose [P < 0.001]). Mean (median)-predicted AE costs for the dose groups were USD $4389 ($2749) for > 0 to ≤ 2607 mg, USD $5176 ($3009) for > 2607 to ≤ 4800 mg, USD $5576 ($3633) for > 4800 to ≤ 7200 mg, and USD $6609 ($4447) for > 7200 mg. CONCLUSION: In patients with GCA, OGC-related AEs increased with increasing cumulative OGC dose, resulting in increased healthcare costs. These results highlight the need for efficacious therapies that reduce the exposure to and potential risks associated with OGCs.

Real-world Comparative Effectiveness of Tocilizumab Monotherapy vs. Tumor Necrosis Factor Inhibitors with Methotrexate in Patients with Rheumatoid Arthritis.

INTRODUCTION: Controlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA. METHODS: TCZ-naïve patients from the Corrona RA registry with prior exposure to ≥ 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI ≤ 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose (≤ 10 mg; > 10 to ≤ 15 mg; > 15 to ≤ 20 mg; > 20 mg); outcomes in each group were compared with TCZ monotherapy using trimmed populations (excluding patients outside the propensity score distribution overlap). RESULTS: Patients in all groups experienced improvement in CDAI at 6 months (mean change, - 6.9 to - 9.7), with no significant differences between the TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6 months were comparable between the TCZ monotherapy and TNFi + MTX groups; overall, 26.8-38.0% of patients achieved LDA, 24.3-37.6% achieved mACR20 response and 13.2-20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was - 0.1 in all groups. CONCLUSIONS: In this real-world population of US patients with RA who had prior TNFi exposure, there was no evidence of a difference in the effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of MTX dose, at 6 months for improving RA disease activity. FUNDING: Corrona, LLC. Plain language summary available for this article.