Comparative Effectiveness of Abatacept vs. Tofacitinib in Rheumatoid Arthritis Patients who are CCP+

Study SampleData Source

The CorEvitas (formerly known as Corrona) RA Registry is an independent, prospective, national, observational cohort. Patients were recruited from 207 private practices and academic sites with 880 participating rheumatologists across 42 states in the US. Treatment and outcomes data for patients with RA are collected and analyzed [14]. As of March 31, 2022, the registry included 217 private and academic active clinical sites with 931 physicians throughout 42 states in the US. Data on 458,982 patient visits and approximately 228,871 patient-years of follow-up observation time have been collected. The mean duration of patient follow-up was 4.8 years (median 3.4 years).

Population

This study selected patients from the CorEvitas Registry who met the following inclusion criteria: RA confirmed by a rheumatologist; ≥ 18 years of age; initiation of abatacept or tofacitinib between December 2012 (when the FDA approved tofacitinib) and October 2019; CCP + (titer ≥ 20 U/ml) any time before starting or at the start of treatment; had a follow-up visit at 6 months (± 3 months) after starting treatment; a Clinical Disease Activity Index (CDAI) score at initiation or prior to treatment initiation and the 6-month follow-up visit; was not in remission based on CDAI at treatment initiation. There were 369 CCP+ abatacept and 475 CCP+ tofacitinib patients who had a 6-month follow-up visit; CDAI at initiation and at 6 months; and were not in remission at the index visit.

Propensity Score Matching

This study performed 1:1 frequency matching by the number of prior biologics (0, 1, or 2+ prior biologics) between abatacept and tofacitinib CCP+ patients. Once matched based on prior biologic use, we assessed the level of imbalance between the abatacept and tofacitinib CCP+ patients using standardized differences.

Standardized differences provide a measure of clinically important difference even if there is no statistically significant difference between the treatment groups [15, 16]. Therefore, we used standardized differences > 0.10 as suggesting meaningful differences between groups. Variables with standardized differences > 0.10 between the groups were considered to have remained potentially unbalanced. After considering standardized differences based on the frequency matching, a propensity score model for treatment (abatacept versus tofacitinib) [16] was fit using the following variables in the final propensity score model: gender, duration of RA, college education, number of prior conventional synthetic (cs) DMARDs (csDMARDs), number of prior bDMARDs, targeted synthetic (ts) DMARDs, follow-up months, baseline CDAI, history of cancer, history of cardiovascular disease (CVD), body mass index (BMI), monotherapy, and prednisone dose > 7.5 at index visit.

We matched the treatment groups and compared characteristics between matched groups using the propensity score. For patients who switched agents during the 6 months of follow-up, we used the outcome measure at the time of switch (rather than at 6 months) for continuous outcomes. For dichotomous outcomes, we imputed them as non-responders (e.g., did not achieve remission for patients that switched prior to their 6-month follow-up visit). For patients who discontinued their medication prior to the follow-up visit without switching to another b/tsDMARD, their outcomes at the follow-up visit were used.

Measures and Data Collection

Data were collected during the study period from physician assessment and patient questionnaires completed during routine clinical visits. These forms were used to gather information on disease severity and activity (including serologic markers) and components of ACR response criteria); comorbidities; use of medications including steroids, csDMARDs, tsDMARDs and bDMARDs; and adverse events. As a strictly observational registry that reflects typical clinical practice, the CorEvitas registry does not mandate that laboratory data, including serologic markers and acute-phase reactants, be performed, however asks participating investigators to submit these results if they were performed.

Data on demographics, insurance status, comorbid conditions, RA disease characteristics, and RA medications were available for > 97% of patients. Data disease activity elements collected included: CDAI; swollen joint count in 28 joints; tender joint count in 28 joints; Physician Global Assessment (PGA) and Patient Global Assessment (PtGA); modified ACR 20, 50, and 70% response criteria (mACR20, mACR50, and mACR70). The mACR is based on achieving the swollen and tender joint responses, as well as two out of four additional measures, including the modified Health Assessment Questionnaire (mHAQ) to assess physical function, patient pain, patient fatigue, and the Patient Global Assessment (PtGA); it does not include erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).

Study Outcomes

The primary outcome was mean improvement in CDAI score over 6 months (± 3 months) following treatment initiation among anti-CCP+ patients treated with abatacept versus tofacitinib. The secondary outcomes compared the response to therapy among CCP+ patients who were treated with abatacept versus tofacitinib at 6 months based on the following outcomes: the achievement of CDAI remission (CDAI score ≤ 2.8); the achievement of CDAI LDA (CDAI score ≤ 10) among those not in remission or LDA at initiation; and achievement of modified ACR20, ACR50, ACR70 responses which included changes from baseline for the modified HAQ (mHAQ), patient pain, patient fatigue, and PtGA. The proportion of patients in each group who discontinued or switched therapies over the study period was assessed.

Statistical Analysis

Patient demographic and disease characteristics at initiation for the two treatment groups were reported with calculated standardized differences. The outcome of response at 6 months was modeled using mixed-effects models. The primary fixed effect of interest was the treatment group (using tofacitinib initiators as the reference group), and site identification was the random effect. After PSM, remaining unbalanced variables, based on standardized differences > 0.10, were included as covariates in the adjusted multivariable models. Covariates included in the multivariable model were age, gender, race, work status, Medicare, blood pressure (systolic), history of non-TNFi DMARD use, baseline CDAI, and mHAQ at index visit.

Compliance with Ethics Guidelines

The study was performed in accordance with the Declaration of Helsinki and the Guidelines for Good Pharmacoepidemiology Practice (GPP). All participating investigators were required to obtain full board approval for conducting noninterventional research involving human subjects with a limited dataset. Sponsor approval and continuing review was obtained through a central Institutional Review Board (IRB), the New England Independent Review Board (NEIRB; no. 120160610). For academic investigative sites that did not receive authorization to use the central IRB, full board approval was obtained from their respective governing IRBs, and documentation of approval was submitted to CorEvitas, LLC before the site’s participation and initiation of any study procedures. All patients in the registry were required to provide written informed consent and authorization before participating.

留言 (0)

沒有登入
gif