Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis

Norman Todd Ilowite, Kristi Prather, Yuliya Lokhnygina, Laura E. Schanberg, Melissa Elder, Diana Milojevic, James W. Verbsky, Steven J. Spalding, Yukiko Kimura, Lisa F. Imundo, Marilynn G. Punaro, David D. Sherry, Stacey E. Tarvin, Lawrence S. Zemel, James D. Birmingham, Beth S. Gottlieb, Michael L. Miller, Kathleen O'Neil, Natasha M. Ruth, Carol A. WallaceNora G. Singer, Christy I. Sandborg

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Objective. To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. Methods. An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in ≥2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary end point was time to response, using the adapted American College of Rheumatology Pediatric 30 criteria coupled with the absence of fever and taper of the dosage of systemic corticosteroids, using prespecified criteria. Results. The time to response was shorter in the rilonacept arm than in the placebo arm (χ2 = 7.235, P = 0.007). The secondary analysis, which used the same response criteria, showed that 20 (57%) of 35 patients in the rilonacept arm had a response at week 4 compared with 9 (27%) of 33 patients in the placebo arm (P = 0.016). Exacerbation of systemic juvenile idio- pathic arthritis (JIA) was the most common severe adverse event. More patients in the rilonacept arm had elevated liver transaminase levels (including levels more than 3 times the upper limit of normal) compared with those in the placebo arm. Adverse events were similar in the 2 arms of the study. Conclusion. Rilonacept was generally well tolerated and demonstrated efficacy in active systemic JIA.

Original languageEnglish (US)
Pages (from-to)2570-2579
Number of pages10
JournalArthritis and Rheumatology
Volume66
Issue number9
DOIs
StatePublished - 2014

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Juvenile Arthritis
Placebos
Safety
Therapeutics
rilonacept
Transaminases
Interleukin-1
Arthritis
Adrenal Cortex Hormones
Fever
Joints
Pediatrics
Liver

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology

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Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis. / Ilowite, Norman Todd; Prather, Kristi; Lokhnygina, Yuliya; Schanberg, Laura E.; Elder, Melissa; Milojevic, Diana; Verbsky, James W.; Spalding, Steven J.; Kimura, Yukiko; Imundo, Lisa F.; Punaro, Marilynn G.; Sherry, David D.; Tarvin, Stacey E.; Zemel, Lawrence S.; Birmingham, James D.; Gottlieb, Beth S.; Miller, Michael L.; O'Neil, Kathleen; Ruth, Natasha M.; Wallace, Carol A.; Singer, Nora G.; Sandborg, Christy I.

In: Arthritis and Rheumatology, Vol. 66, No. 9, 2014, p. 2570-2579.

Research output: Contribution to journalArticle

Ilowite, NT, Prather, K, Lokhnygina, Y, Schanberg, LE, Elder, M, Milojevic, D, Verbsky, JW, Spalding, SJ, Kimura, Y, Imundo, LF, Punaro, MG, Sherry, DD, Tarvin, SE, Zemel, LS, Birmingham, JD, Gottlieb, BS, Miller, ML, O'Neil, K, Ruth, NM, Wallace, CA, Singer, NG & Sandborg, CI 2014, 'Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis', Arthritis and Rheumatology, vol. 66, no. 9, pp. 2570-2579. https://doi.org/10.1002/art.38699
Ilowite, Norman Todd ; Prather, Kristi ; Lokhnygina, Yuliya ; Schanberg, Laura E. ; Elder, Melissa ; Milojevic, Diana ; Verbsky, James W. ; Spalding, Steven J. ; Kimura, Yukiko ; Imundo, Lisa F. ; Punaro, Marilynn G. ; Sherry, David D. ; Tarvin, Stacey E. ; Zemel, Lawrence S. ; Birmingham, James D. ; Gottlieb, Beth S. ; Miller, Michael L. ; O'Neil, Kathleen ; Ruth, Natasha M. ; Wallace, Carol A. ; Singer, Nora G. ; Sandborg, Christy I. / Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis. In: Arthritis and Rheumatology. 2014 ; Vol. 66, No. 9. pp. 2570-2579.
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abstract = "Objective. To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. Methods. An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in ≥2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary end point was time to response, using the adapted American College of Rheumatology Pediatric 30 criteria coupled with the absence of fever and taper of the dosage of systemic corticosteroids, using prespecified criteria. Results. The time to response was shorter in the rilonacept arm than in the placebo arm (χ2 = 7.235, P = 0.007). The secondary analysis, which used the same response criteria, showed that 20 (57{\%}) of 35 patients in the rilonacept arm had a response at week 4 compared with 9 (27{\%}) of 33 patients in the placebo arm (P = 0.016). Exacerbation of systemic juvenile idio- pathic arthritis (JIA) was the most common severe adverse event. More patients in the rilonacept arm had elevated liver transaminase levels (including levels more than 3 times the upper limit of normal) compared with those in the placebo arm. Adverse events were similar in the 2 arms of the study. Conclusion. Rilonacept was generally well tolerated and demonstrated efficacy in active systemic JIA.",
author = "Ilowite, {Norman Todd} and Kristi Prather and Yuliya Lokhnygina and Schanberg, {Laura E.} and Melissa Elder and Diana Milojevic and Verbsky, {James W.} and Spalding, {Steven J.} and Yukiko Kimura and Imundo, {Lisa F.} and Punaro, {Marilynn G.} and Sherry, {David D.} and Tarvin, {Stacey E.} and Zemel, {Lawrence S.} and Birmingham, {James D.} and Gottlieb, {Beth S.} and Miller, {Michael L.} and Kathleen O'Neil and Ruth, {Natasha M.} and Wallace, {Carol A.} and Singer, {Nora G.} and Sandborg, {Christy I.}",
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T1 - Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis

AU - Ilowite, Norman Todd

AU - Prather, Kristi

AU - Lokhnygina, Yuliya

AU - Schanberg, Laura E.

AU - Elder, Melissa

AU - Milojevic, Diana

AU - Verbsky, James W.

AU - Spalding, Steven J.

AU - Kimura, Yukiko

AU - Imundo, Lisa F.

AU - Punaro, Marilynn G.

AU - Sherry, David D.

AU - Tarvin, Stacey E.

AU - Zemel, Lawrence S.

AU - Birmingham, James D.

AU - Gottlieb, Beth S.

AU - Miller, Michael L.

AU - O'Neil, Kathleen

AU - Ruth, Natasha M.

AU - Wallace, Carol A.

AU - Singer, Nora G.

AU - Sandborg, Christy I.

PY - 2014

Y1 - 2014

N2 - Objective. To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. Methods. An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in ≥2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary end point was time to response, using the adapted American College of Rheumatology Pediatric 30 criteria coupled with the absence of fever and taper of the dosage of systemic corticosteroids, using prespecified criteria. Results. The time to response was shorter in the rilonacept arm than in the placebo arm (χ2 = 7.235, P = 0.007). The secondary analysis, which used the same response criteria, showed that 20 (57%) of 35 patients in the rilonacept arm had a response at week 4 compared with 9 (27%) of 33 patients in the placebo arm (P = 0.016). Exacerbation of systemic juvenile idio- pathic arthritis (JIA) was the most common severe adverse event. More patients in the rilonacept arm had elevated liver transaminase levels (including levels more than 3 times the upper limit of normal) compared with those in the placebo arm. Adverse events were similar in the 2 arms of the study. Conclusion. Rilonacept was generally well tolerated and demonstrated efficacy in active systemic JIA.

AB - Objective. To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. Methods. An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in ≥2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary end point was time to response, using the adapted American College of Rheumatology Pediatric 30 criteria coupled with the absence of fever and taper of the dosage of systemic corticosteroids, using prespecified criteria. Results. The time to response was shorter in the rilonacept arm than in the placebo arm (χ2 = 7.235, P = 0.007). The secondary analysis, which used the same response criteria, showed that 20 (57%) of 35 patients in the rilonacept arm had a response at week 4 compared with 9 (27%) of 33 patients in the placebo arm (P = 0.016). Exacerbation of systemic juvenile idio- pathic arthritis (JIA) was the most common severe adverse event. More patients in the rilonacept arm had elevated liver transaminase levels (including levels more than 3 times the upper limit of normal) compared with those in the placebo arm. Adverse events were similar in the 2 arms of the study. Conclusion. Rilonacept was generally well tolerated and demonstrated efficacy in active systemic JIA.

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