Pilot study comparing the Childhood Arthritis & Rheumatology Research Alliance (CARRA) systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans

Yukiko Kimura, Sriharsha Grevich, Timothy Beukelman, Esi Morgan, Peter A Nigrovic, Kelly Mieszkalski, T Brent Graham, Maria Ibarra, Norman Ilowite, Marisa Klein-Gitelman, Karen Onel, Sampath Prahalad, Marilynn Punaro, Sarah Ringold, Dana Toib, Heather Van Mater, Jennifer E Weiss, Pamela F Weiss, Laura E Schanberg, CARRA Registry Investigators, L Abramson, E Anderson, M Andrew, N Battle, M Becker, H Benham, T Beukelman, J Birmingham, P Blier, A Brown, H Brunner, A Cabrera, D Canter, D Carlton, B Caruso, L Ceracchio, E Chalom, J Chang, P Charpentier, K Clark, J Dean, F Dedeoglu, B Feldman, P Ferguson, M Fox, K Francis, M Gervasini, D Goldsmith, G Gorton, B Gottlieb, T Graham, T Griffin, H Grosbein, S Guppy, H Haftel, D Helfrich, G Higgins, A Hillard, J R Hollister, J Hsu, A Hudgins, C Hung, A Huttenlocher, N Ilowite, A Imlay, L Imundo, C J Inman, J Jaqith, R Jerath, L Jung, P Kahn, A Kapedani, D Kingsbury, K Klein, M Klein-Gitelman, A Kunkel, S Lapidus, S Layburn, T Lehman, C Lindsley, M Macgregor-Hannah, M Malloy, C Mawhorter, D McCurdy, K Mims, N Moorthy, D Morus, E Muscal, M Natter, J Olson, K O'Neil, K Onel, M Orlando, J Palmquist, M Phillips, L Ponder, S Prahalad, M Punaro, D Puplava, S Quinn, A Quintero, C Rabinovich, A Reed, C Reed, S Ringold, M Riordan, S Roberson, A Robinson, J Rossette, D Rothman, D Russo, N Ruth, K Schikler, A Sestak, B Shaham, Y Sherman, M Simmons, N Singer, S Spalding, H Stapp, R Syed, E Thomas, K Torok, D Trejo, J Tress, W Upton, R Vehe, E von Scheven, L Walters, J E Weiss, P F Weiss, N Welnick, A White, J Woo, J Wootton, A Yalcindag, C Zapp, L Zemel, A Zhu, Yukiko Kimura, Sriharsha Grevich, Timothy Beukelman, Esi Morgan, Peter A Nigrovic, Kelly Mieszkalski, T Brent Graham, Maria Ibarra, Norman Ilowite, Marisa Klein-Gitelman, Karen Onel, Sampath Prahalad, Marilynn Punaro, Sarah Ringold, Dana Toib, Heather Van Mater, Jennifer E Weiss, Pamela F Weiss, Laura E Schanberg, CARRA Registry Investigators, L Abramson, E Anderson, M Andrew, N Battle, M Becker, H Benham, T Beukelman, J Birmingham, P Blier, A Brown, H Brunner, A Cabrera, D Canter, D Carlton, B Caruso, L Ceracchio, E Chalom, J Chang, P Charpentier, K Clark, J Dean, F Dedeoglu, B Feldman, P Ferguson, M Fox, K Francis, M Gervasini, D Goldsmith, G Gorton, B Gottlieb, T Graham, T Griffin, H Grosbein, S Guppy, H Haftel, D Helfrich, G Higgins, A Hillard, J R Hollister, J Hsu, A Hudgins, C Hung, A Huttenlocher, N Ilowite, A Imlay, L Imundo, C J Inman, J Jaqith, R Jerath, L Jung, P Kahn, A Kapedani, D Kingsbury, K Klein, M Klein-Gitelman, A Kunkel, S Lapidus, S Layburn, T Lehman, C Lindsley, M Macgregor-Hannah, M Malloy, C Mawhorter, D McCurdy, K Mims, N Moorthy, D Morus, E Muscal, M Natter, J Olson, K O'Neil, K Onel, M Orlando, J Palmquist, M Phillips, L Ponder, S Prahalad, M Punaro, D Puplava, S Quinn, A Quintero, C Rabinovich, A Reed, C Reed, S Ringold, M Riordan, S Roberson, A Robinson, J Rossette, D Rothman, D Russo, N Ruth, K Schikler, A Sestak, B Shaham, Y Sherman, M Simmons, N Singer, S Spalding, H Stapp, R Syed, E Thomas, K Torok, D Trejo, J Tress, W Upton, R Vehe, E von Scheven, L Walters, J E Weiss, P F Weiss, N Welnick, A White, J Woo, J Wootton, A Yalcindag, C Zapp, L Zemel, A Zhu

Abstract

Objectives: To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry.

Methods: Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months.

Trial registration: clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled).

Results: Thirty patients were enrolled at 13 sites; eight patients were started on a non-biologic CTP (2 GC, 6 MTX) and 22 patients on a biologic CTP (12 IL1i, 10 IL6i) at disease onset. Demographic and disease features were similar between CTP groups. CTP choice appeared to segregate by site preference. CID off GC was achieved by 37% (11 of 30) including 11/22 (50%) starting a biologic CTP compared to 0/8 starting a non-biologic CTP (p = 0.014). There were four serious adverse events: two infections, one appendicitis and one macrophage activation syndrome.

Conclusions: The CARRA systemic JIA CTP pilot study demonstrated successful implementation of CTPs using the CARRA registry infrastructure. Having demonstrated feasibility, a larger study using CTP response to better determine the relative effectiveness of treatments for new-onset systemic JIA is now underway.

Keywords: Biologic response modifiers; Comparative effectiveness; Pediatric rheumatology; Registries; Still’s disease; Systemic Juvenile Idiopathic Arthritis.

Figures

Fig. 1
Fig. 1
Initial Consensus Treatment Plan (CTP) Choices and Subsequent Treatment Changes. The total numbers of patients started on each CTP are shown, along with those remaining on the original CTP medication (dark blue), switching to a different CTP (green) or adding another CTP medication (light blue). IL1i: IL1 inhibitor; IL6i: IL6 inhibitor
Fig. 2
Fig. 2
Initial Consensus Treatment Plan (CTP) Choice By Site. CTP choices distributed by site, showing that 4 sites started only a non-biologic CTP (red colors), while 8 sites started only a biologic CTP (blue colors), IL1i: IL1 inhibitor; IL6i: IL6 inhibitor

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