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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/12139

Title: Identification of Anti-TNF Candidates Based on Predicted Response and Remission in Ankylosing Spondylitis
Authors: Vastesaeger, Nathan
Inman, Robert
Wang, Yanxin
Deodhar, Atul
Hsu, Benjamin
Rahman, Mahboob
Dijkmans, Ben
Seiper, Joachim
Braun, Juergen
Issue Date: 2011
Citation: JOURNAL OF RHEUMATOLOGY, 38(6). p. 1144-1144
Abstract: Objectives: To identify subpopulations of Ankylosing Spondylitis (AS) patients who are candidates for anti-tumor necrosis factor (TNF) based on the predicted response/remission rates. Methods: The ASSERT and GO-RAISE trial data were analyzed separately and combined, and matrix models were developed to predict probability for achieving response or remission after initiating anti-TNF therapy or continuing conventional AS therapy. In the separate and combined datasets, univariate analysis identified possible baseline predictors for 50% improvement in Bath AS Disease Activity Index Score (BASDAI50) at wk 12 and Assessments in AS (ASAS) partial remission at wk 24 (Student t-test or χ2 at the p<0.1 level). Individual variable associations were explored using Spearman correlation analysis. A stepwise selection procedure using multivariate regression, ROC analysis and Spearman correlation was used to select predictors for the final model. Variables are represented as dichotomous or trichotomous parameters, and logistic regression was used to calculate the predicted probability of achieving a BASDAI50 response and ASAS partial remission respective to combined selected predictors at baseline. Results: 479 AS patients (NY modified criteria) treated with anti-TNF and 156 patients treated with placebo with continued conventional therapy (NSAIDs +/- DMARDs +/- corticosteroids), with BASDAI and spinal pain assessment ≥ 4 were included. Age (mean 39.5; SD 11.4 yrs), Bath AS Functional Index score (BASFI, mean 5.4; SD 2.2 cm), Berlin enthesitis-score (Enthesitis; mean 2.4; SD 2.9), therapy (anti-TNF or conventional), C-reactive protein (CRP, mean 2.1; SD 2.4 mg/dL) and HLA-B27 genotype [(+) or (-)] were included as predictors. The area under the ROC curve for BASDAI50 response at week 12 was 82%, 75% and 77% and 80%, 77% and 78% for ASAS partial remission at wk 24 for ASSERT, GO-RAISE and the combined data respectively. After categorization of age (≤40 vs. >40 yrs), enthesitis (score =0 vs. >0 units), CRP (≤0.6, >0.6 ≤2.0, >2.0 mg/dL) and BASFI (≤4.5, >4.5 ≤6.5, >6.5 cm), the AUC of the combined dataset prediction model was 80% for BASDAI50 response and 77% for ASAS partial remission suggesting a good prediction model according to the academic point system. A matrix model was developed and organized to represent increasing proportion of BASDAI50 response (range 1% to 80%) and ASAS partial remission (range 0% to 54%) respective to the characteristic at baseline from left to right, bottom to top. Only 2% of patients who did not have BASDAI50 response at week 12 had ASAS partial remission at week 24. Conclusion: The majority of AS patients who have elevated disease activity and back pain respond to anti-TNF therapy while few respond to continued conventional therapy. Young patients and patients without peripheral enthesitis receiving anti-TNF therapy demonstrate an improved response. CRP, functionality and HLA-B27 measurements can help in assessing which patients will respond and subsequently achieve an improved disease state and who therefore might be better candidates for anti-TNF therapy.
Notes: [Van der Heijde, D] Leiden Univ, Med Ctr, Leiden, Netherlands [Inman, R] Univ Toronto, Toronto, ON, Canada [Deodhar, A] Oregon Hlth & Sci Univ, Portland, OR 97201 USA [Hsu, B] Centocor Res & Dev Inc, Malvern, PA USA [Rahman, M] Univ Penn, Centocor R&D, Malvern, PA USA [Geusens, P] Univ Hasselt, Hasselt, Belgium [Seiper, J] Rheum Charite Hosp, Berlin, Germany
URI: http://hdl.handle.net/1942/12139
ISI #: 000292534500062
ISSN: 0315-162X
Category: M
Type: Journal Contribution
Appears in Collections: Research publications

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