New Juvenile Arthritis Therapies
Adalimumab, Abatacept receive FDA approval for kids
By Robin Yamakawa
Children with juvenile arthritis now have two more FDA-approved options when it comes to exploring treatment choices. The biologic medications adalimumab (Humira) and abatacept (Orencia) were approved by the FDA back to back in February and April, respectively.
Adalimumab, an anti-TNF agent, was approved for use as a treatment to reduce the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) inpatients 4 years of age and older. Abatacept was approved for use to reduce signs and symptoms in children and adolescents 6 years of age and older with moderate to severe polyarticular juvenile idiopathic arthritis (JIA).
“To have two medications approved weeks apart for JRA is blockbuster,” says Dan Lovell, MD, MPH, Associate Director of the Division of Rheumatology at Cincinnati Children’s Hospital Medical Center. “In the history of drug development for juvenile arthritis we’ve only come up with one [other biologic FDA approved for children] so for these to be approved is great.”
More choice
FDA approval means wider availability of these medications, presenting new choices for kids who haven’t been able to tolerate or haven’t had success with other treatments. “There is no one biologic that works for every patient so it’s important to have options,” says Dr. Lovell.
In general, biologic therapies work at the cellular level of the immune system, changing the way inflammation in your body works. Because of these effects on the immune system, all biologic medications pose an increased risk of infection and related side effects. Different biologics work to stop inflammation through different ways, or mechanisms. Adalimumab blocks a protein involved in inflammation called TNF and abatacept adjusts the way certain T cells work.
With these approvals, Dr. Lovell says, adalimumab may become a biologic option prescribed to children before trying other biologics, or it may be a choice for children who have failed another anti-TNF medication. As Dr. Lovell explains, you can fail one anti-TNF and have success with another. In clinical trials, Dr. Lovell says, abatacept worked for a number of patients who had failed anti-TNF therapy and it seemed to be well tolerated.
Drug differences
Adalimumab
This medication is given through injections. Its approval was based on data from a study of 171 children age 4 to 17 that had active moderate to severe disease despite previous treatment with multiple medications. In the 48-week study, fewer children treated with adalimumab experienced disease flare compared to placebo.
The study was made of up two parts. In the first, it tested adalimumab in two groups of children, those who were taking methotrexate and those who were not. In the first part of the study both the methotrexate and nonmethotrexate groups were given adalimumab for 16 weeks. Children who improved then were put in the second part of the trial. Those children were randomly divided into two groups and either continued on adalimumab or given a placebo (a shot containing no medicine) for 32 weeks or until disease flare.
Patient responses were measured using the American College of Rheumatology Pediatric(ACR Pedi) 30 score, which represents a 30percent or greater improvement in JIA signs and symptoms, such as the number of swollen joints with loss of motion, assessment of pain and level of disability. A flare was defined as a worsening of 30 percent or more in at least three of the six ACR Pedi response variables, a minimum of two active joints, and no more than one indicator improving by 30 percent.
In the second part of the study, significantly fewer children receiving adalimumab flared, whether they were on methotrexate or not. Forty three percent of children given the drug flared compared to 71 percent of those on placebo. And, 37 percent of those on both methotrexate and adalimumab flared compared to 65 percent of children receiving methotrexate and placebo.
Efficacy and safety were assessed throughout the study. Injection site pain and injection site reaction were the most common adverse reactions. This happened in under 20 percent of children. Overall, improvements were maintained for up to two years in patients who received adalimumab throughout the study.
Abatacept
This medication is given through infusions. Like adalimumab, it may be used alone or in combination with methotrexate. It should not be used along with TNF blockers or other biologics. Its FDA approval was based on the AWAKEN trial in which the medication was studied for efficacy and safety in children age 6 to 17 with moderately to severely active JIA who had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs), such as methotrexate or anti-TNF biologic.
The three-part study lasted one year. It began with 190 children who had had arthritis for approximately four years and a majority of whom had not used a biologic before. The trial was made up of children with oligoarticular, polyarticular and systemic types of JIA. About 30 percent had previously had an inadequate response to a TNF blocker or anakinra.
In the first part of the study, which lasted four months, all of the children received abatacept. Improvement and flare was based on the ACR Pedi 30. In the second part of the trial, those children who had success on abatacept either continued on abatacept or started the placebo for six months. This part of the study ended when flare occurred. In the third part, children were allowed to get back on abatacept if they were given the placebo or continue treatment if they were on abatacept all along.
Overall, patients treated with abatacept experienced significantly fewer disease flares compared to placebo patients – 20 percent on abatacept had flare while 53 on placebo did. If the child continued on abatacept, his risk of disease flare was one-third than that of children who withdrew from abatacept treatment.
Throughout the study adverse reactions were similar in type and frequency to those seen in adult patients. Infection occurred 36percent of the time in part one of the study. The most common infections were respiratory tract infection and nasopharyngitis. For additional information on adverse risks for both adalimumab and abatacept, speak with your child’s doctor.
Other benefits to approval
In addition to adding new treatment options to the market, FDA approval may mean increased financial access to these medications. With approval, insurers are more likely to consider covering the costs of these medications, says Dr. Lovell. That’s important to take into consideration because biologic prescriptions can cost thousands of dollars a year.
Manufacturers may also offer prescription assistance programs to make their medications more affordable. One non-profit clearinghouse for information on financial assistance information is the Partnership for Prescription Assistance, www.pparx.org. There, you can find information on both public and private financial assistance programs for which you may be eligible. You can also call 888-477-2669.
For more information on these medications and their possible suitability for treating your child, speak with your child’s doctor.
Source: Kids Get Arthritis Too, Arthritis Foundation. For more articles from this newsletter, visit www.arthritis.org/ja-kgat.
