Abatacept: Safe and Effective for Treating Juvenile Idiopathic Arthritis
Juvenile idiopathic arthritis (JIA) is one of the most common rheumatologic diseases that affect children, and its etiology is still largely unknown. But while the cause of JIA might be veiled, finding effective medications that are safe to use over long periods of time is paramount. A recently published article suggests that abatacept (Orencia) maybe such a treatment.
Abatacept is a selective T Cell costimulation modulator, a safe short-term alternative to etanercept, or Enbrel, for the treatment of JIA.1-3 According to the new study published online in Arthritis and Rheumatology, abatacept may be just as effective, and perhaps safer, in a long-term treatment setting.4
An international team of researchers looked at 153 JIA patients (aged 6-17 years), who had been culled from a previous open-label 4-month study with abatacept.2 Entering a long-term extension (LTE) of the the phase III, placebo-controlled trial, 76 patients received intravenous abatacept (10 mg/kg, with a maximum dose at 1,000 mg/kg) or placebo (n=76) for up to 7 years.4
All of the patients had a mean disease duration of 4.1 years and an average of 16 joints that showed active disease and serious disability. During the 4-month trial and into the LTE, JIA American College of Rheumatology (ACR) responses, which define a percentage of improvement in the core variables of the disease, showed positive numbers. Of the 63 patients who received 4.8 years of active treatment, 58 (92.1%), 45 (71.4%), and 27 (42.9%) patients achieved JIA ACR scores of 30, 70 and clinically inactive disease states, respectively. For non-responders (n=13), who may have dropped out of treatment for various reasons, they showed similar improvements, at 9 (69.2%), 7 (53.8%), and 4 (30.8%), respectively.
The patients’ quality of life showed marked improvements. Prior to treatment, Child Health Questionnaire scores were lower than those of healthy children, but after starting with abatacept, the patients reported noticeable initial improvements1 that continued into the LTE, until scores were back into normal range. Pain scores also dropped consistently through the LTE, with improvements in sleep quality, as well.
Chronic Condition, Chronic Treatment
JIA is a chronic condition that can have an early onset in young patients. While various medications, like abatacept, etanercept (Enbrel), and adalimumab (Otezla), are promising options as biologic treatments, testing the long-term safety of these drugs is essential, as patients may end up taking these medications for years. For instance, etanercept has a safe 8-year safety record.5 (Learn more about integrative treatments for JIA).
However, there are times when abatacept is the more appropriate biologic agent, according to lead author of the study Daniel J Lovell, MD, MPH, from the Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio.
Etanercept is a tumor necrosis factor (TNF) blocker, so patients with tuberculosis or Hepatitis B can suffer from worsening conditions while taking it. In the long term, anti-TNF agents also can increase the risk of various cancers, like lymphoma and skin cancer, and those with a family history of multiple sclerosis are advised to stay away from them.
Some patients may prefer abatacept’s method of administration, as well, Dr. Lovell said. While etanercept treatments are home-based subcutaneous injections, children get abatacept treatments through a convenient, once-monthly intravenous infusion.
While taking abatacept during the study, the rate of adverse events and serious adverse events, like infections, didn’t increase relative to the short-term, 4-month study phase. Interestingly, some adverse events, particularly autoimmune events, actually decreased in comparison to the short-term phase.
In total, 6 patients taking abatacept had to discontinue the LTE due to adverse events: urticaria, bronchospasm, worsening vitiligo, skin lesions, temporal lobe epilepsy, multiple sclerosis, appendicitis, and bacterial arthritis. However, besides worsening arthritis, no adverse event was reported by more than 2 patients.
Also, it’s unknown whether these adverse events were related directly to the abatacept treatment, as a majority of the patients were taking multiple concomitant medications upon entering the LTE, notably methotrexate (75.2%), or Trexall.6 Now considered a first-line defense for rheumatoid arthritis, this folic acid inhibitor has its own association with adverse events.
“The attribution of blame is very difficult to do in these patients taking multiple drugs,” Dr. Lovell said. Other concomitant medications the patients were taking included folic acid (72.5%), oral corticosteroids (41.2%), intra-articular corticosteroid injections (15%), and nonbiologic disease-modifying anti-rheumatic drug (DMARD) (12.4%).
The fact that only 69 (45%) of the patients remained in the LTE until the end presents a notable limitation. Out of the 84 who discontinued, 24 dropped out because of lack of efficacy using abatacept.
However, the researchers noted that these numbers shouldn’t be surprising. Of those that discontinued before the end of the LTE, over 50% did so for other reasons than lack of efficacy or safety concern. With 36.3% of the patients still using abatacept up to year 7, the discontinuation rate was actually on par with other biologic agents, like infliximab (Remicade, others) 7 and etanercept.5
Unfortunately, while doctors continue to research safety and efficacy profiles of biologic agents for JIA, it’s still difficult to judge medications side-by-side with uniform clinical data. Dr. Lovell said the key is developing a trusted registry of retrospective and prospective studies—something that’s already becoming a reality with the nationwide CARRA Registry. New treatments are in the pipeline, as well.
“There are lots of new biologic agents being developed, for both adults and children,” with 6 active protocols currently in development, Dr. Lovell said. In particular, he mentioned Jak inhibitors, a new class of pharmaceuticals recently approved by the FDA that work by blocking cytokine signaling through targeted Janus kinases.8 The first agent approved by the FDA was tofacitinib (Xeljanz) in 2012. Jak inhibitors work through a novel mechanism, and since they can be administered in pill form, they present an oral approach atypical to other biologic agents.