Placeholder TextIntraarticular steroids as DMARD-sparing agents for juvenile idiopathic arthritis flares: Analysis of the Childhood Arthritis and Rheumatology Research Alliance Registry

For children with JIA who flare after discontinuing treatment with a systemic medication, IAS injections are an option that may eliminate or delay the need to restart systemic medications. This study is the first to report on the proportion of patients who restart a systemic medication after being treated with IAS.

In our study, the majority of patients who required treatment after discontinuing a systemic medication were treated with a systemic medication (139/185) which is consistent with what has been reported by other groups [13, 14]. The higher cJADAS, joint count, and physician global assessment in this group treated with systemic medications suggest that disease activity at the time of a flare is a determinant of the treatment of choice. However, the finding that 50% of the patients with only a single joint involved were treated with systemic medication and that the cJADAS was not statistically significantly different between the two groups suggests that factors other than disease activity also contribute to the decision to use a systemic treatment. Physicians may have made treatment decisions based on the specific joint involved, availability of certain steroid preparations, and the success of prior injections in a given joint. Prior studies have demonstrated that these and other factors may contribute to the success of treatment with IAS [16,17,18]. It is also possible that the patients’ and/or caregivers’ familiarity with a previously used medication may ameliorate some of the hesitancy that is commonly encountered at the initiation of treatment with methotrexate or biologics.

Of the variables analyzed, only a history of biologic use was associated with failure of IAS. Biologics are typically used in patients who have either failed methotrexate or have clinical features at presentation that have been shown to predict methotrexate failure [1, 19, 20]. We suspect that the association of biologic use with IAS failure is indicative of the presence of a more aggressive disease process in a subset of patients which limits the clinical response to methotrexate and IAS.

Additionally, the observation that the distribution of JIA subtypes was not different between the group that failed IAS treatment for flare and those who did not fail seems to support the evolving hypothesis that the biologic phenotype may be more important for treatment decisions than the clinical phenotype in some patients [21]. The data do not allow us to determine whether the reason for IAS failure was due to arthritis resistant to IAS or accumulation of new joints after IAS. However, from a patient’s perspective this differentiation may not matter, since either scenario would lead to restarting systemic therapy.

The results of this analysis should be immediately impactful for pediatric rheumatologists as well as patients and their families. Patients who previously required a biologic DMARD for treatment of JIA who flare after discontinuing treatment should restart their biologic DMARD due to the high rate of failure of treatment with an IAS injection. Conversely, patients that were treated with methotrexate without the need for a biologic DMARD are good candidates for treatment with an IAS injection. This treatment approach would likely be well received by children and their families, especially considering the high frequency of methotrexate associated morbidity.

The greatest strength of this study is the large sample size contained within the CARRA Registry. There are some important limitations in this study. The Registry does not collect detailed information about medical decision making. There is also no indication of which joint is involved or which steroid dose and preparation were used for injections. Prior studies have shown variability in joint specific response to IAS with knees and wrists responding better than ankles and midfoot joints [18, 22]. Unfortunately, due to the lack of consistent availability of triamcinolone hexacetonide in the past decade, it is likely that some patients in this cohort received injections with the shorter-acting triamcinolone acetonide, potentially introducing bias into the results. Future studies should control for the specific joint, steroid preparation, and dose of steroid [23]. We also did not account for NSAID use given the frequent use of NSAIDs as needed, for brief periods of time, and for non-rheumatologic reasons (menstrual cramps, headaches etc.). Additionally, the CARRA Registry does not systematically collect data about NSAID use. The generalizability of these results are limited by the fact that the patients treated with IAS appeared to have less active disease at the time of flare. A limited number of patients had lab data available at the time of IAS injection which limited our ability to evaluate the differences in biomarkers, such as ESR. Nevertheless, this is the first report on this topic and these results should help facilitate discussion between patients, families and providers when faced with certain treatment decisions. While these results are informative, more data are needed to determine the most appropriate treatment of disease flares in patients with JIA flares who have been in a state of inactive disease.

In summary, a subset of patients with JIA who flare after discontinuing systemic medication may be successfully treated with IAS without needing to restart systemic medication. Patients with more benign disease course, indicated by the lack of a need for a biologic, may be better candidates for IAS treatment. Improved understanding of the biologic processes and heterogeneity in JIA may improve our ability provided targeted treatment.

List of abbreviations: JIA, Juvenile Idiopathic Arthritis. DMARD, Disease modifying anti-rheumatic drugs. IAS, Intraarticular steroid. CARRA, Childhood Arthritis Rheumatology Research Alliance. ILAR, International League Against Rheumatism. JC, Joint count. cJADAS, Clinical Juvenile Arthritis, Disease Activity Score. ANA, Antinuclear Antibodies, RF, Rheumatoid Factor. CCP, Cyclic Citrullinated Peptide.

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