Predictors and Sustainability Of Clinical Inactive Disease In Polyarticular Juvenile Idiopathic Arthritis Given Aggressive Therapy Very Early In The Disease Course

Carol A. Wallace¹, Edward H. Giannini², Steven J. Spalding³, Philip J. Hashkes⁴, Kathleen M. O'Neil⁵, Andrew S. Zeft⁶, Ilona S. Szer⁷, Sarah Ringold⁸, Hermine Brunner⁹, Laura E. Schanberg¹⁰, Robert P. Sundel¹¹, Diana Milojevic¹², Marilynn G. Punaro¹³, Peter Chira¹⁴, Beth S. Gottlieb¹⁵, Gloria C. Higgins¹⁶, Norman T. Ilowite¹⁷, Yukiko Kimura¹⁸, Anne Johnson⁹, Bin Huang¹⁹ and Daniel J. Lovell², ¹University of Washington School of Medicine and Seattle Children's Hospital, Seattle, WA, ²Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ³Pediatric Institute, Department of Pediatric Rheumatology, The Cleveland Clinic, Cleveland, OH, ⁴Pediatrics, Shaare-Zedek Medical Center, Jerusalem, Israel, ⁵Pediatric Rheumatology, Riley Hospital for Children, Indianapolis, IN, ⁶Pediatric Institute, Department of Pediatric Rheumatology, Cleveland Clinic Foundation, Cleveland, OH, ⁷Div of Rheumatology, Rady Childrens Hosp San Diego, San Diego, CA, ⁸Pediatrics, Seattle Children's Hospital/Univ of Washington, Seattle, WA, ⁹Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ¹⁰Pediatrics, Duke University Medical Center, Durham, NC, ¹¹Division of Immunology, Boston Children's Hospital, Boston, MA, ¹²Dept of Pediatric Rheumatology, University of California, San Francisco, San Francisco, CA, ¹³Pediatric Rheumatology, Texas Scottish Rite Hospital, Dallas, TX, ¹⁴Pediatric Rheumatology, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN, ¹⁵Pediatric Rheumatology, Cohen Children's Medical Center of New York, New Hyde Park, NY, ¹⁶Pediatric Rheumatology Ohio State University, Nationwide Childrens Hosp, Columbus, OH, ¹⁷Pediatrics, The Children's Hospital at Montefiore, Bronx, NY, ¹⁸Pediatric Rheumatology, Joseph M Sanzari Children’s Hospital, Hackensack University Medical Center, Hackensack, NJ, ¹⁹Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center/University of Cincinnati School of Medicine, Cincinnati, OH

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Clinical Response, juvenile idiopathic arthritis (JIA), patient outcomes, pediatric rheumatology and remission

Session Information

Title: Pediatric Rheumatology: Clinical and Therapeutic Disease: Juvenile Idiopathic Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose:

The double-blind, randomized placebo-controlled Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis (TREAT) compared the ability of 2 aggressive treatment regimens to produce clinical inactive disease (CID) within 6 mos of starting therapy. An exploratory phase lasting up to 1 year from baseline determined if patients could achieve CID after switching to the more aggressive treatment arm (M-E-P: etanercept 0.8 mg/kg/wk, MTX 0.5 mg/kg/wk given subcutaneously, prednisolone 0.5 mg/kg/d tapered to zero by 17 wks) from the less aggressive arm (MTX: MTX as in the M-E-P Arm, placebo prednisolone, placebo etanercept ), and achieve clinical remission on medication (CRM; 6 continuous mos of CID). The purposes of this analysis were to determine lapsed time on-therapy to the first occurrence, and sustainability of CID and if predictors of CID exist.

Methods: Eighty-five patients aged 2-17 yrs with active RF (+) or (-) polyarticular JIA (poly-JIA) less than 12 mos in duration (median 4.2 mos) were randomized to either M-E-P (N=42) or MTX (N=43) and assessed for CID using the Wallace Criteria at mos 1, 2, 4, 5, 6, 7, 8, 10 and 12 mos or discontinuation. Patients in either group who failed to achieve an ACR Pedi 70 at 4 mos, or CID at 6 mos were switched to open-label M-E-P for the remainder of the study. Descriptive measures, the Mann-Whitney U and Fisher’s Exact tests were the chief statistical methods.

Results:

CID was observed at least once in 30 (71%) of those who started on M-E-P and in 28 (65%) of MTX starts (17 of these 28 achieved CID only after switching to open-label M-E-P). Median number of days on aggressive therapy until the first occurrence of CID was 168.5 and 192 for those who started M-E-P and MTX groups respectively. M-E-P starts spent a median of 139.5 (42%) days of follow-up with CID, compared to a median of 79 (24%) days for MTX starts (p=0.016). M-E-P starts had CID at 117 of 347 (34%) follow-up visits while MTX starts had CID at 81 of 337 (24%) visits. When data were combined from the blinded and open-label (all patients receiving M-E-P) phases, CID was observed at 154 of 481 (32%) visits by patients on M-E-P, compared to 43 of 203 (21%) visits while receiving MTX alone.

Baseline characteristics were not statistically predictive of CID except for disease duration prior to enrollment. Patients with duration ≤3 mos at enrollment had CID at a median of 40% of visits, while those with disease >3 mos had CID for a median of only 11% of visits (p<0.0001).

Among 49 patients who achieved an ACR Pedi 70 at 4 mos, 42 (86%) attained CID, compared to 16 of 36 (44%) who failed to achieve the early response (p=0.0001). All 12 patients (9 M-E-P and 3 MTX) who achieved CRM met the ACR Pedi 70 at 4 mos.

Conclusion: Aggressive therapy given early in the disease course of poly-JIA results in a large proportion of patients achieving CID within 12 mos. There is a tendency for a combination of an anti-TNF agent, MTX and prednisolone to produce more sustainable CID than does high dose MTX monotherapy. A short disease duration prior to start of aggressive therapy and attainment of an ACR Pedi 70 by 4 mos are significant predictors of achieving sustained CID.

Disclosure:

C. A. Wallace,

Amgen,

Pfizer Inc,

Novartis Pharmaceutical Corporation,

E. H. Giannini,
None;

S. J. Spalding,
None;

P. J. Hashkes,
None;

K. M. O’Neil,

UCB,

A. S. Zeft,

Pfizer Inc,

I. S. Szer,
None;

S. Ringold,
None;

H. Brunner,

Novartis, Genentech, Medimmune, EMD Serono, AMS, Pfizer, UCB, Jannsen,

Genentech,

L. E. Schanberg,

Novartis Pharmaceutical Corporation,

Lilly,

UCB,

Amgen,

BMS,

SOBI,

Pfizer Inc,

R. P. Sundel,
None;

D. Milojevic,
None;

M. G. Punaro,
None;

P. Chira,
None;

B. S. Gottlieb,
None;

G. C. Higgins,
None;

N. T. Ilowite,

Novartis Pharmaceutical Corporation,

Janssen Pharmaceutica Product, L.P.,

Y. Kimura,
None;

A. Johnson,
None;

B. Huang,
None;

D. J. Lovell,

Astra Zeneca, Centocor, Hoffman-La Roche, Novartis, UBC,

Amgen, Forest Research,

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