Predictors of Response to Anti-TNF Therapy in Ankylosing Spondylitis: Results From the British Society for Rheumatology Biologics Register
Lord PA, Farragher TM, Lunt M, Watson KD, Symmons DPM, Hyrich KL; BSR Biologics Register
Rheumatology (Oxford). 2010;49:563-570. Epub 2009 Dec 23
Several antitumor necrosis factor (anti-TNF)-alpha agents are approved for use in ankylosing spondylitis (AS). However, limited data are available outside of clinical trials in regard to what clinical factors may predict a good response to anti-TNF-alpha therapy. Knowing which patients with AS may benefit most from such therapy may help providers use these expensive agents more judiciously. These authors used the British Society for Rheumatology Biologics Register (BSRBR) to identify factors in patients outside of clinical trials that were associated with improvement in AS disease treated with anti-TNF-alpha therapy, with disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI).
Two hundred sixty-one patients with AS treated with an anti-TNF agent (etanercept, infliximab, and adalimumab) were identified from the BSRBR (median age, 43 years old; 82% men; median disease duration, 13 years). Baseline and 6-month measures for BASDAI and BASFI were obtained, and improvements in the 6-month values for these instruments were used as outcomes. The BASDAI consists of 6 visual analogue scales measuring patient-reported fatigue, pain (spinal and peripheral), swelling (peripheral joints), tenderness, and morning stiffness; it is scored 0-10, with 10 indicating more severe disease. The BASFI evaluates patient-reported functional status and consists of 10 visual analogue scales assessing the ability of a patient to perform various activities; it is scored 0-10, with 10 indicating more disability. At 6 months, mean BASDAI and BASFI scores fell by 3.6 units and 2.6 units, respectively. In multivariate analyses, a higher baseline BASDAI score predicted a larger improvement at 6 months. Additionally, elevated erythrocyte sedimentation rates or C-reactive protein at baseline also predicted larger improvement in BASDAI. However, BASFI scores (measure of disability) showed less improvement than BASDAI scores, although female sex, higher baseline BASFI scores, and anti-TNF plus disease-modifying antirheumatic drug use were associated with greater improvement in BASFI scores. No comparison of score improvements between the anti-TNF agents was performed due to inadequate sample size. The authors concluded that higher baseline BASDAI scores and elevated erythrocyte sedimentation rates/C-reactive protein predict improved scores in response to anti-TNF therapy, and that these measures may identify patients who are more responsive to therapy.
Given the expense and risk profiles of anti-TNF agents, measures that can identify which patients will benefit most from these agents prior to their initiation will be of great benefit. In this interesting study, it appears that higher BASDAI scores and elevated inflammatory markers predict greater improvements in BASDAI. Of interest, there was less improvement in the BASFI, perhaps due to this instrument's measurement of disability, which may reflect irreversible damage from disease rather than reversible inflammatory activity. Going forward, we'll need to determine how the anti-TNF agents improve scores over longer periods of time, as well as gain more data on the effect of anti-TNF agents in preventing spinal fusion in AS. For now, a take-home point from this report is that higher baseline disease activity as measured by BASDAI and inflammatory markers may, in "real-world" treatment (ie, not in a clinical trial), help to identify patients who will have greater short-term symptomatic response to therapy.