Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis

Abstract

Background: TNFalpha blockers have been shown to be highly efficacious in patients with active ankylosing spondylitis (AS).

Objective: To identify parameters predicting the clinical response to TNF blockers in AS.

Methods: Patients with active AS participated in two placebo controlled, randomised trials conducted in Germany with infliximab (n = 69) and etanercept (n = 30), respectively. For inclusion in either trial patients had to have high disease activity (BASDAI >or=4) and a spinal pain score (numerical rating scale 0-10) >or=4 despite treatment with NSAIDs. A major clinical response was defined as a 50% improvement of the initial BASDAI (BASDAI 50) after 12 weeks' treatment with active drug. Logistic regression likelihood ratio tests (univariate and multivariate), Student's t test, and chi(2) tests were performed.

Results: Univariate analysis showed the following to be predictors of a major response (BASDAI 50) to treatment: shorter disease duration (p = 0.003); lower BASFI (p = 0.007); younger age (p = 0.009); raised ESR (p = 0.033); raised CRP (p = 0.035). After adjustment for disease duration, BASFI, ESR, and CRP, but not age, remained significantly associated. After adjustment for disease duration and for BASFI, ESR, CRP, and in addition, a higher BASDAI were significantly associated with response. The best multivariate model built by stepwise regression contained the covariables disease duration, BASFI, BASDAI, and CRP.

Conclusion: A shorter disease duration, younger age, and a lower BASFI are predictors of a major clinical response to TNF blockers in active AS. Raised CRP and a higher BASDAI may also be valuable predictors. These data need to be confirmed in further studies.

Figure 1

Relationship between disease duration and proportion of patients (%) who achieved a BASDAI 50 response after 12 weeks. Here, patients (n = 99) were grouped into three blocks of disease duration (⩽10 years, 11–20 years, >20 years). Patients with shorter disease duration had a significantly higher chance of achieving BASDAI 50 than patients with longer disease duration (χ² = 11.7; p = 0.003).

Figure 2

Relationship between functional status (BASFI) and proportion of patients (%) who achieved a BASDAI 50 response after 12 weeks. Patients (n = 99) were grouped into blocks of various BASFI scores. Patients with lower BASFI scores (that is, better functional status) had a significantly higher chance of achieving BASDAI 50 than patients with higher BASFI scores (that is, worse functional status) (χ² = 8.2; p = 0.017).

Figure 3

Relationship between disease activity (BASDAI) and proportion of patients (%) who achieved a BASDAI 50 response after 12 weeks. Patients (n = 99) were grouped into blocks of various BASDAI scores. Patients with a BASDAI >5 had a significantly higher chance of achieving BASDAI 50 than patients with a BASDAI of 4–5 (OR = 3.8, 95% CI 1.2 to11.7; p = 0.024).

Figure 4

Probability of a BASDAI 50 response after 12 weeks depending on CRP levels at baseline and disease duration. The three curves were calculated by bivariate logistic regression analysis. They represent the expected probabilities of response for three selected levels of disease duration (5 years, 15 years, 25 years) and various levels of CRP.