We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A12: The Role of Serum S100A12 Protein Levels in Disease Flare After Withdrawal of Anti-tumor Necrosis Factor Therapy in Polyarticular Forms of Juvenile Idiopathic Arthritis.
- Authors
Hinze, Claas; Foell, Dirk; Johnson, Anne; Kimura, Yukiko; Spalding, Steven J.; Morris, Paula W.; Gottlieb, Beth; Onel, Karen; Olson, Judyann C.; Edelheit, Barbara; Shishov, Michael; Jung, Lawrence; Cassidy, Elaine; Prahalad, Sampath; Passo, Murray H.; Beukelman, Timothy; Mehta, Jay; Schmidt, Kara M.; Giannini, Edward H.; Lovell, Daniel J.
- Abstract
Background/Purpose: Anti-TNF therapy for polyarticular forms (extended oligo-, rheumatoid factor +/− polyarthritis) of JIA (PF-JIA) results in up to 50% of patients (pts) demonstrating clinically inactive disease (CID). This study determined the pattern of serum S100A12 levels at the time of withdrawal of anti-TNF therapy. Methods: In 16 centers, 137 pts with PF-JIA in CID on anti-TNF therapy were enrolled and followed for at least 14 months (mos). During the first 6 study mos pts were maintained on anti-TNF therapy and if CID was maintained, then anti-TNF therapy was stopped. Background medications were stable. S100A12 levels were obtained at the time of anti-TNF withdrawal. The primary outcome was disease 'flare' defined by worsening of ≥30% in ≥ 3 of the 6 core set variables, with no more than 1 improving by ≥30%. Parameters had to increase by at least the following amounts: MD and parent globals by 2 units, active and limited joints by 2, CHAQ by 0.125 and ESR from normal to abnormal. Results: 24 pts failed to maintain CID in the first 6 study mos and 7 pts were discontinued from the study for other reasons. 106 pts were available for this analysis of whom 39 (37%) experienced flare. The S100A12 levels at time of anti-TNF withdrawal did not differ significantly in regards to JIA type, presence of ANA, MTX co-therapy, or type of anti-TNF therapy and did not correlate with previous duration of CID. Globally, S100A12 at the time of withdrawal did not differ significantly according to disease flare (flare 73 +/− 117 ng/ml, no flare 80 +/− 220 ng/ml) (median ++/− standard deviation). Receiver-operating curve (ROC) analysis computing S100A12 at time of anti-TNF withdrawal against flare for the entire study period demonstrated an area-under-the-curve (AUC) of 0.51, 95% confidence interval (CI) 0.39-0.62, for prediction of flare within 60 days AUC 0.66, 95% CI 0.56-0.75, for prediction of flare within 90 days AUC 0.64, 95% CI 0.54-0.74 and for prediction of flare within 120 days AUC 0.54, 95% CI 0.44-0.64. The S100A12 level at time of withdrawal correlated inversely with the time to flare (Spearman rank correlation = −0.34, p = 0.05). Flares occurred earlier in pts with predefined high (>120 ng/ml) vs. low (≤120 ng/ml). S100A12 levels at time of withdrawal among pts who flared (median time to flare 36 vs. 114 days, p = 0.02). The overall flare rate in patients with high vs. low S100A12 levels at time of withdrawal was 35% vs. 38%, respectively. Kaplan-Meier analysis of disease flare in pts with high vs. low S100A12 levels at time of withdrawal also demonstrated a trend towards earlier disease flare in pts with high S100A12 levels (log rank test significance 0.07). Conclusion: In this prospective study, a substantial proportion of pts with PF-JIA experienced disease flare after anti-TNF withdrawal. Serum S100A12 levels at time of anti-TNF withdrawal did not differ between pts subsequently experiencing disease flare and those not experiencing flare throughout the entire study period. However, pts with high S100A12 levels (>120 ng/ml) experienced earlier disease flare.
- Subjects
CONFIDENCE intervals; PROTEINS; JUVENILE idiopathic arthritis; TUMOR necrosis factors; DETOXIFICATION (Substance abuse treatment); DISEASE relapse; DISEASE remission; RECEIVER operating characteristic curves; KAPLAN-Meier estimator; LOG-rank test; CHEMICAL inhibitors
- Publication
Arthritis & Rheumatology, 2014, Vol 66, pS19
- ISSN
2326-5191
- Publication type
Article
- DOI
10.1002/art.38423