Sara Freeman

HLA-B27 Predicts TNF-Inhibitor Response in AS

LONDON – In the 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, and [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. “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. 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, 1.3333.87; 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 0to 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.” ■ Costly agents reduce symptoms of AS, but not everyone benefits.

Data Do Not Justify Use of CAM in Rheumatic Diseases

B I R M I N G H A M , E N G L A N D — Musculoskeletal ultrasound of multiple small joints is more accurate than traditional clinical assessment at predicting patient outcomes in very early arthritis, judging from the results of a pilot investigation. “Musculoskeletal ultrasound is not routinely used for diagnosing arthritis [in the United Kingdom],” according to Dr. Andrew Filer, who noted that there have been few studies of the technique for the prediction of patient outcome. “We know that if we treat patients early they do better, not only in the short term but also in the long term,” he added. “The trouble is, not all patients come through the door with a confirmed diagnosis of rheumatoid or psoriatic arthritis,” said Dr. Filer, who is senior lecturer at the University of Birmingham and consultant rheumatologist at Sandwell and West Birmingham Hospitals NHS Trust. He is also a member of the Rheumatology Research Group at the University of Birmingham. At the meeting, Dr. Filer reported the preliminary results of an ongoing study designed to determine if musculoskeletal ultrasound can help predict which patients with very early arthritis actually develop rheumatoid arthritis (RA) or related conditions. The researchers recruited 58 patients who had inflammatory joint symptoms of 3 months or less duration and clinically apparent inflammation of at least one joint. Half of the cohort (50%, 29) had RA, with 48% (14) having detectable anti-citrullinated peptide antibodies. Sixteen (27.6%) patients had resolving arthritis, which was mostly unclassified, and 13 (22.4%) patients had persistent conditions other than RA. The non-RA group included five patients with psoriatic arthritis, one with reactive arthritis, and two with systemic lupus erythematous. Disease could not be classified in 5 patients. Patients were assessed clinically before undergoing musculoskeletal ultrasound within 24 hours, and followed up prospectively for 18 months. Baseline and follow-up clinical assessments included 68 tender and 66 swollen joint counts; 28-joint disease activity score; serological data; and conventional radiography of the hands and feet. An ultrasonographer, who was unaware of the clinical findings, systematically assessed a total of 50 joints using four-point semi-quantitative scales to note the presence of erosions. Musculoskeletal ultrasound detected significantly more joint involvement than did clinical examination. It also detected more clinically silent involvement of the wrist, elbow, knee, ankle, and metatarsophalangeal (MTP) region. Sensitivity and specificity analyses showed that ultrasound images of the wrist, metacarpophalangeal (MCP) region, and MTP region were the best predictors of joint involvement, improving upon clinical predictive models for RA. In contrast, imaging of the large joints was not useful for predicting joint involvement. ■