In July 2012, a group of researchers from CARRA (the Childhood Arthritis and Rheumatology Research Alliance) issued recommendations to help doctors standardize treatment plans for children with systemic juvenile idiopathic arthritis (sJIA). With the introduction of biologics in the past decade, the number of drugs used to treat sJIA has dramatically increased. Unfortunately, there are no studies directly comparing these drugs in patients with sJIA. Before these recommendations, clinicians used their own experience to develop treatment plans, resulting in a wide variation in drugs used, dosage, and timing, etc. The consensus treatment plan helps provide greater consistency in treatment. Perhaps more importantly, it will help researchers understand the best ways treat the disease.
In other rare diseases (like certain childhood cancers), similar consensus treatment plans have helped successfully identify the most successful treatment regimens. Ultimately this has also dramatically decreased deaths from these diseases. With rare disease like sJIA, there is a special challenge in doing carefully controlled scientific studies. Something called Ã¢â‚¬Å“comparative researchÃ¢â‚¬Â can help find answers in these conditions. Scientists can compare how different patients respond to different treatments that have already been given. In order to perform such studies, itÃ¢â‚¬â„¢s important that researchers look at groups of patients who received identical or very similar treatments.
The 2012 CARRA guidelines aimed to reduce variations in treatments for children with sJIA during their first nine months of treatment. The guidelines also helped create a centralized database for tracking treatment outcomes. Over time, use of these guidelines should help researchers determine which medications are most effective, safest, and which have the fewest side effects.
The guidelines present four possible treatment plans for sJIA, providing information about standard dosing. The guidelines also provide clinicians with standard recommendations about how often to reassess patients and how to alter the treatment plan as symptoms change.
Here is a brief summary of the four treatment plans:
a) The first of the four possible plans centers on treatment with steroid drugs (glucocorticoids). Doctors initially treat with these drugs alone. At follow up assessments, steroid amounts are decreased (if symptoms have improved), continued at the same dosage (if symptoms are unchanged), or increased (if symptoms are worse). If patients havenÃ¢â‚¬â„¢t improved at three months, doctors add additional drugs under the guidance of plans b, c, or d.
b) Under the second treatment plan, affected children initially receive the drug methotrexate and possibly additional steroids. At follow up appointments, doctors might remove the steroids if symptoms have improved. If symptoms are unchanged or worsened, they may increase the dosage of steroids or methotrexate. If symptoms havenÃ¢â‚¬â„¢t improved at three months, doctors add additional drugs under plans c or d.
c) Plan c uses the drug anakinra (brand name Kineret). This is a newer type of drug in the Ã¢â‚¬Å“biologicsÃ¢â‚¬Â classÃ¢â‚¬â€drugs made to mimic special substances normally made by the immune system. Under this plan, doctors start with anakinra with optional steroids. At follow up appointments, they might remove the steroids if symptoms have improved. If symptoms are unchanged or worsened, they may increase the dosage of steroids or anakinra. If symptoms havenÃ¢â‚¬â„¢t improved at three months, doctors add additional drugs under plans b or d.
d) The final plan uses another biologic drug, tocilizumab (trade name Actemra). Under this plan, doctors start with tocilizumab with optional steroids. At follow up appointments, they might remove the steroids if symptoms have improved. If symptoms are unchanged or worsened, they may increase the dosage of steroids or tocilizumab. If symptoms havenÃ¢â‚¬â„¢t improved by three months, doctors add additional drugs under plans b or c.
In each of the treatment plans, clinicians assess and may modify treatment at intervals after initial assessment, at two weeks, one month, and three months.
Which of these treatment plans is best for the initial treatment of sJIA? Currently, there are not enough data to know, though all the drugs can help treat the disease to a certain extent. Hopefully doctors can learn the answer to this question in coming years as they compare how patients fare after receiving one of these four treatment plans.
Since the introduction of the suggested treatment plans, many pediatric rheumatologists have adopted them. If your child is newly diagnosed with sJIA, the rheumatologist will probably follow one of these treatment plans. If so, you might be asked for permission to participate in a study using the CARRA centralized database. You may want to ask your doctor if your childÃ¢â‚¬â„¢s treatment falls under the CARRA guidelines and see if this treatment can be used in research. Participating in such studies is a powerful way to help advance the sJIA field. Ultimately, all of us will benefit from understanding the best way to treat sJIA patients.