Session Information
Date: Tuesday, November 15, 2016
Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects II: Juvenile Arthritis
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Although the recommended first line treatment for JIA, up to 50% of children will not respond to MTX. Currently, it is not possibly to identify at the start of therapy which children will not respond and thus initiation of effective therapies may be delayed. The aim of this analysis was to identify clinical factors measured at the outset of therapy associated with non-response to MTX with a view towards building an accurate multifactorial prediction model.
Methods: Children with JIA treated with MTX were identified from four large multi-centre UK observational studies participating in the Childhood Arthritis Response to Treatment (CHART) consortium: Childhood Arthritis Prospective Study, British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study, Biologics for Children with Rheumatic Diseases Study, and Childhood Arthritis Response to Medication Study. Demographic, clinical and laboratory variables at start of MTX and at 6 (4-12) months following treatment start were extracted and combined using a common data model. Non-response at 6-months was defined as lack of achievement of the ACR Pediatric (ACR Pedi) 30 criteria or initiation of biologics due to MTX inefficacy. Patients stopping MTX prematurely (< 4 months) due to intolerance were excluded. Each potential predictor of non-response was evaluated using logistic regression. Significant factors were taken into a multivariate logistic regression model and estimated using stepwise backward elimination approach. Missing data including outcome data was addressed using multiple imputations.
Results: A total of 2211 patients were included in this analysis, mean age at MTX start 8.4years, 68% female, 41% polyarthritis, 34% oligoarthritis, 7% psoriatic, 8% systemic onset, 4% undifferentiated and 6% enthesitis related arthritis. The non-response rate (95%CI) was 32.7% (30.2 – 35.0). In the multivariate model, only lower ESR, Physician global assessment (PGA), Parent’s general evaluation of well-being (PGE), ANA negativity and use of oral MTX versus subcutaneous route were significantly associated with non-response (Table 1), AUC 66.6%.There was no significant association between age, gender, disease duration, BMI, JIA subtype, joint counts and CHAQ score and non-response to MTX at 6 months.
Conclusion: Although some routinely collected clinical and laboratory factors were associated with non-response in this large JIA cohort, overall, clinical factors alone could not predict non-response to MTX. The addition of biological or genetic factors to clinical factors may be able to identify a more robust model to predict non-response and divert children onto more effective therapies earlier in their disease course.
|
of MTX therapy that were significant in univariate analysis |
Non-responders 32.7% (30.2 – 35.0) |
Responders
67.3% (64.9 – 69.7) |
OR (95% CI) |
P value |
| Active joint count (median, IQR) | 4(2,8) | 6(3,10) | 0.97(0.96-0.99) |
0.004 |
| Limited joint count(median, IQR) | 3 (1,6) | 4 (2,7) | 0.96(0.95-0.98) |
<0.0001 |
| CHAQ score (median, IQR) | 0.8(0.3,1.5) | 1.1(0.5,1.7) | 0.66(0.56-0.77) |
<0.0001 |
| ESR (median, IQR) | 17 (7,40) | 28 (10, 55) | 0.99(0.98-0.99) |
<0.0001 |
| PGA (median, IQR) | 3.1 (2.0,5.0) | 4.0 (2.8, 7.5) | 0.83(0.78-0.88) |
<0.0001 |
| PGE (median, IQR) | 3.1 (1.0, 5.2) | 4.8 (2.1, 6.8) | 0.87(0.83-0.91) |
<0.0001 |
| Age at MTX start in years (median, IQR) | 9.1 (4.3 , 12.8) | 8.1 (3.8, 11.9) | 1.03(1.01-1.06) |
0.004 |
| Disease duration in months (median, IQR) | 12.6(5.9,32.1) | 9.2(4.5,25.4) | 1.00(1.00-1.01) |
0.01 |
| Route of MTX |
1.57(1.20-2.07) |
0.001 |
||
| Subcutaneous(95%CI) | 23.0%(18.1-27.9) | 32.1%(28.3-35.7) | ||
| Oral(95%CI) | 76.9%(72.1-81.8) | 67.9%(64.2-71.7) | ||
| ANA status |
0.74(0.57-0.96) |
0.02 |
||
| ANA positive(95% CI) | 47.9%( 42.9-52.8%) | 55.2%(51.6-58.7) | ||
| ANA negative(95%CI) | 52.1%(47.1-57.1) | 44.8(41.2-57.1) | ||
| Final Multivariable Model | ||||
| Predictors of non-response | OR (95% CI) | |||
| ESR | 0.99(0.99-0.99) | |||
| PGA | 0.89(0.83-0.95) | |||
| PGE | 0.91(0.85-0.96) | |||
| MTX by oral route | 1.43(1.07-1.9) | |||
| ANA positive | 0.73(0.56-0.96) | |||
| AUC = 66.6% Hosmer-Lemeshow goodness of fit statistic, p = 0.1 | ||||
Table 1: Factors Significantly Associated with Non-response to MTX and results of Final Multivariable Model
To cite this abstract in AMA style:
Sampath S, Sergeant JC, Viatte S, Carrasco R, Cobb J, Smith S, Hinks A, Wedderburn LR, Beresford MW, Hyrich KL, Thomson W. Clinical Factors Associated with Non-Response to Methotrexate in Children with Juvenile Idiopathic Arthritis: Results from the Childhood Arthritis Response to Treatment Consortium [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/clinical-factors-associated-with-non-response-to-methotrexate-in-children-with-juvenile-idiopathic-arthritis-results-from-the-childhood-arthritis-response-to-treatment-consortium/. Accessed .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-factors-associated-with-non-response-to-methotrexate-in-children-with-juvenile-idiopathic-arthritis-results-from-the-childhood-arthritis-response-to-treatment-consortium/