SLR - August 2014 - Nha Thanh Pham
Longterm Safety, Efficacy, and Inhibition of Structural Damage Progression Over 5 Years of Treatment with Abatacept in Patients with Rheumatoid Arthritis in the Abatacept in Inadequate Responders to Methotrexate Trial
Reference: Kremer JM, Peterfy C, Russell AS, Emery P, Abud-Mendoza C, Sibilia J, Becker JC, Westhovens R, Genant HK. Longterm Safety, Efficacy, and Inhibition of Structural Damage Progression Over 5 Years of Treatment with Abatacept in Patients with Rheumatoid Arthritis in the Abatacept in Inadequate Responders to Methotrexate Trial. Journal of Rheumatology. 2014; 41; 1077-1087.
Scientific Literature Review
Reviewed By: Nha Thanh Pham, DPM
Residency Program: Hoboken University Medical Center
Podiatric Relevance: Rheumatoid arthritis (RA) is an autoimmune disease that commonly affects the small joints of hands and feet. Unlike osteoarthritis, RA affects multiple symmetrical joints of the body. When it concerns podiatric care, RA causes a variety of pathology including joint damage which leads to biomechanic changes, heel pain, nerve entrapment, skin problems with formation of rheumatoid nodules. Treatment of RA focuses on controlling of symptom as well as anti-inflammatory regimen and biologic therapy such as Methotrexate (MTX) and Abatacept (ABA). This article is a report of the five-year findings from the largest phase III trial of ABA in patients with RA and an inadequate response to MTX. It also evaluates the effect of ABA on safety and tolerability, clinical efficacy, and structural damage progression over the long term.
Methods: Abatacept in inadequate responders to Methotrexate trial (AIM) included a one-year, double-blind (DB), placebo-controlled period, in which patients with active RA and inadequate response to MTX were randomized in a 2:1 ratio to either ABA or placebo, both plus MTX. Patients who completed the one-year DB period were eligible to enter an open-label long term extension (LTE). During the LTE, adjustments to MTX dose and other drugs were permitted at the discretion of the investigator. Safety assessments were performed monthly and included adverse events and discontinuation. Efficacy assessments were performed quarterly during the LTE until year four and at six-month intervals thereafter. Mean changes from baseline in erosion scores, joint space narrowing, and total scores were assessed using the Genant-modified Sharp scoring method.
Results: Out of 652 patients, 539 entered the LTE. At year 5, 72.4 percent were ongoing. Discontinuation rates declined over time. Incidence rate for serious adverse effect were reported at 13.87 events/100 patient-years. Nineteen deaths reported in total during the cumulative study period, two events were considered as related to the studied drug. Incidence report for infection was 67.14 events/100 patient-years. Malignancies were reported in 28 patients in the LTE. Autoimmune events occurred at an incidence report (IR) of 0.99 events/100 patient-years. For patient originally randomized to placebo who switched to ABA treatment during LTE, improvements in clinical efficacy were observed over their four years of treatment. For patients originally randomized to placebo who switched to ABA treatment during the LTE, reduced radiographic progression was also observed over four years following.
Conclusions: The LTE of the AIM study evaluated the longterm safety, radiographic benefits, and clinical efficacy of ABA treatment in RA patients with inadequate response to MTX. Overall, treatment with ABA over a period of five years was well tolerated. Patients with RA have an increased risk of infection and malignancies. The IR of serious infection in the cumulative ABA experience is at the lower end of the range observed in patients with RA treated with other biologics. In the AIM trial, treatment with ABA resulted in persistent radiographic inhibition over time, with almost half exhibiting no structural damage progression. These data support the longterm use of ABA in patients with RA who have inadequate response to MTX.