With regard to tracking disease activity, the Clinical Juvenile Arthritis Disease Activity Score-10 (cJADAS-10) includes a physician global assessment, parent/guardian or patient global assessment and number of joints with active arthritis up to a maximum of 10. Dr. Fuhlbrigge explained that the cJADAS-10 can be used to determine if a patient has low, moderate or high disease activity, allowing for treat-to-target approaches that may help improve patients’ quality of life and prevent damage from their disease.
Dosing Optimization
Ruud Verstegen, MD, PhD, assistant professor and clinical investigator in the Division of Clinical Pharmacology and Toxicology, Division of Rheumatology, The Hospital for Sick Children, Toronto, discussed treatment optimization. He noted that although many treatment options exist for patients with JIA, 33% of patients won’t respond to a given treatment and 5–10% of patients will have loss of response over the course of a year. Response and lack or loss of response are dictated by the interplay between the characteristics of the patient, the disease and the pharmacotherapeutic elements of the medication in question.
An important difference in the dosing of medications, such as adalimumab and etanercept, for pediatric vs. adult patients is the use of weight-based dosing. For adalimumab and similar medications, a specific dose is given every other week for patients who fall into a range of weights. Thus, a patient at the lower end of the weight range will receive a higher mg/kg dose of adalimumab than a patient at the upper end of the weight range who is getting the same absolute dose.
Dr. Verstegen has studied real-world dosing variations and evaluated for correlation with treatment response. In patients studied from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, Dr. Verstegen and his team found that, for each mg/kg dose increase with adalimumab or etanercept, there was no change in the odds ratio for achieving low disease activity via cJADAS-10. (Note: This study has not been published.)
With respect to therapeutic drug monitoring, Dr. Verstegen showed a schematic that may be helpful to clinicians. In cases of treatment failure (i.e., non-response or loss of response), the first step is to measure a trough serum drug concentration. If this trough is detectable, then the best next step would be to switch the class of the medication. If the trough is undetectable, then anti-drug antibodies can be measured. If anti-drug antibodies are negative, then this finding may mean the issue is treatment adherence or an inappropriately low dose for that patient. This factor can be corrected by encouraging adherence or increasing the dose. If anti-drug antibodies are positive, then it may be worthwhile to switch to a treatment within the same class of medication.
Treatment Withdrawal
Finally, medication withdrawal was discussed by Daniel Horton, MD, MSCE, assistant professor of pediatrics and epidemiology, Rutgers Robert Wood Johnson Medical School and Rutgers School of Public Health, New Brunswick, N.J. Dr. Horton provided a conceptual model to consider regarding medication withdrawal after achieving disease inactivity in patients with JIA. This model is based on four elements:
- Factors associated with flare after withdrawal;
- Strategies for treatment withdrawal;
- Timing of withdrawal and use of biomarkers; and
- Shared decision making with patients and their families.
Factors associated with flare after withdrawal may include anti-nuclear antibody positivity, older age at uveitis diagnosis, delay of initiation of biologic therapy, delay in achieving inactive disease and the need for biologic therapy. Dr. Horton noted many methods may be used to withdraw treatment, including stopping treatment immediately, tapering and changing the interval of dosing. Evidence indicates fewer flares occur in patients on combination therapy if methotrexate is stopped before discontinuing treatment with a tumor necrosis factor-α inhibitor.2,3
