LONDON – In an everyday setting, HLA-B27 positivity is the strongest predictor of an early, good response to the first use of an anti-tumor necrosis factor agent in patients with ankylosing spondylitis, according to the results of a longitudinal, observational study.
Other "real-world" and independent predictors of a good response using the ankylosing spondylitis disease activity score (ASDAS) are younger age, male sex, a higher baseline C-reactive protein (CRP) level, and a higher baseline patient global assessment score.
"TNF [tumor necrosis factor] inhibitors are effective in reducing symptoms in ankylosing spondylitis [AS], but not all patients have a response, [they] sometimes have side effects, and the medication is expensive," said Karen Fagerli, Ph.D., of the department of rheumatology at Diakonhjemmet Hospital in Oslo.
Karen M. Fagerli
"So we want to identify characteristics of patients who will have a response in order to potentially utilize this knowledge when selecting patients for TNF-inhibitor therapy, and [therefore] treat patients with an optimized benefit-to-risk ratio," Dr. Fagerli added. ASDAS was used as the main outcome measure, which may be the first time it has been used in an observational study setting.
Using data from the NOR-DMARD (Norway-Disease-Modifying Antirheumatic Drug) register, researchers identified a study population of 171 patients with AS who were starting a TNF-inhibitor for the first time. The aim was to identify predictors of response to this treatment using the recently developed ASDAS outcome measure.
NOR-DMARD is a large, observational register that includes all patients with inflammatory arthropathies who are starting treatment with a DMARD for the first time at five rheumatology centers in Norway. Patients are routinely assessed at baseline, then after 3, 6, and 12 months, and then annually.
ASDAS major improvement was defined as a change in score of 2 or more; this was achieved by 32.7% of patients after 3 months of anti-TNF therapy.
Several parameters that had been identified as predictors of response in univariate analysis did not hold up as being statistically significant in a multivariate analysis model; these included the number of swollen joints, physician’s global score, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Bath Ankylosing Spondylitis Functional Activity Index (BASFAI).
Patients who were HLA-B27 positive had a much higher chance of achieving ASDAS major improvement at 3 months than did those who were HLA-B27 negative (odds ratio, 6.72; 95% confidence interval, 1.33-33.87; P = .02).
Baseline CRP levels higher than 10 mg/L were also significantly predictive of an early treatment response (OR, 5.31; 95% CI, 2.23-12.42; P less than .001).
The next strongest predictor was male sex, with men almost three times more likely than women to show a benefit of anti-TNF treatment at 3 months (OR, 2.69; 95% CI, 1.04-7.00; P less than .04). However, the majority of the study population (73.4%) was male.
For every 1-year increase in age, the likelihood of achieving ASDAS major improvement declined, with young patients faring the best overall (OR, 0.95; 95% CI, 0.91-1.00; P less than .03).
Furthermore, for every 10-mm increase in a 0- to 100-mm visual analog scale of patient global assessment, the chance of a good response improved (OR, 1.75; 95% CI, 1.40-2.19; P less than .0001).
Taken together, these data could help clinicians to identify patients who not only may respond to anti-TNF inhibitors but also should be prioritized for such treatment.
However, "this is on a crude level; we don’t know to what extent we can use [this information] on an individual level," Dr. Fagerli said in an interview. "We know for certain that there are patients who have none of these characteristics that I’ve talked about, who do get a response, so this is not the full truth; this is a little piece of the puzzle."
Dr. Fagerli disclosed receiving a speaker’s fee from Pfizer in the past.