N. Vastesaeger

Predicting the outcome of ankylosing spondylitis therapy

Objectives To create a model that provides a potential basis for candidate selection for anti-tumour necrosis factor (TNF) treatment by predicting future outcomes relative to the current disease profile of individual patients with ankylosing spondylitis (AS). Methods ASSERT and GO–RAISE trial data (n=635) were analysed to identify baseline predictors for various disease-state and disease-activity outcome instruments in AS. Univariate, multivariate, receiver operator characteristic and correlation analyses were performed to select final predictors. Their associations with outcomes were explored. Matrix and algorithm-based prediction models were created using logistic and linear regression, and their accuracies were compared. Numbers needed to treat were calculated to compare the effect size of anti-TNF therapy between the AS matrix subpopulations. Data from registry populations were applied to study how a daily practice AS population is distributed over the prediction model. Results Age, Bath ankylosing spondylitis functional index (BASFI) score, enthesitis, therapy, C-reactive protein (CRP) and HLA-B27 genotype were identified as predictors. Their associations with each outcome instrument varied. However, the combination of these factors enabled adequate prediction of each outcome studied. The matrix model predicted outcomes as well as algorithm-based models and enabled direct comparison of the effect size of anti-TNF treatment outcome in various subpopulations. The trial populations reflected the daily practice AS population. Conclusion Age, BASFI, enthesitis, therapy, CRP and HLA-B27 were associated with outcomes in AS. Their combined use enables adequate prediction of outcome resulting from anti-TNF and conventional therapy in various AS subpopulations. This may help guide clinicians in making treatment decisions in daily practice.

The epidemiology of ankylosing spondylitis and the commencement of anti-TNF therapy in daily rheumatology practice

Objectives: This study aimed to describe the epidemiology of ankylosing spondylitis (AS) in rheumatology practice at the beginning of the anti-TNF (tumour necrosis factor) era, and to evaluate the initiation of anti-TNF therapy in a clinical setting where prescription is regulated by the authority’s imposed reimbursement criteria. Methods: Between February 2004 and February 2005, all Belgian rheumatologists in academic and non-academic outpatient settings were invited to register all AS patients who visited their practice. A random sample of these patients was further examined by an in-depth clinical profile. In a follow-up investigation, we recorded whether patients initiated anti-TNF therapy and compared this to their eligibility at baseline evaluation. Results: 89 rheumatologists participated and registered 2141 patients; 1023 patients were clinically evaluated. These 847 fulfilled the New York modified criteria for definite AS and 176 for probable AS. The profile of AS in rheumatology practice is characterised by longstanding and active disease with a high frequency of extra-articular manifestations and metrological and functional impairment. At a median of 2 months after the clinical evaluation, anti-TNF therapy was initiated in 263 of 603 (44%) evaluable patients with definite AS and in 22 of 138 (16%) evaluable patients with probable AS (total 38%). More than 85% of the patients who started anti-TNF therapy had an increased Bath Ankylosing Spondylitis Disease Activity Index despite previous NSAID (non-steroidal anti-inflammatory drug) use. Conclusions: Of a representative cohort of 1023 Belgian AS patients seen in daily rheumatology practice, about 40% commenced anti-TNF therapy. Decision factors to start anti-TNF therapy may include disease activity and severity.

Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1.

Objectives To assess whether combination therapy with infliximab (IFX) plus nonsteroidal anti-inflammatory drugs (NSAIDs) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society (ASAS) partial remission in patients with early, active axial spondyloarthritis (SpA) who were naïve to NSAIDs or received a submaximal dose of NSAIDs. Methods Patients were randomised (2 : 1 ratio) to receive naproxen (NPX) 1000 mg daily plus either IFX 5 mg/kg or placebo (PBO) at weeks 0, 2, 6, 12, 18 and 24. The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28. Several other measures of disease activity, clinical symptoms and patient-rated outcomes were evaluated. Treatment group differences were analysed with Fisher exact tests or analysis of covariance. Results A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group (61.9%; 65/105) than in the PBO+NPX group (35.3%; 18/51) at week 28 (p=0.002) and at all other visits (p<0.05, all comparisons). Results of most other disease activity and patient-reported endpoints (including Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, multiple quality of life measures and pain measures) showed greater improvement in the IFX+NPX group than the PBO+NPX group, with several measures demonstrating early and consistent improvement over 28 weeks of treatment. Conclusions Patients with early, active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone. NPX alone led to clinical remission in a third of patients.

Hip involvement in ankylosing spondylitis: epidemiology and risk factors associated with hip replacement surgery

OBJECTIVES Although clinicians recognize hip involvement, which frequently leads to hip replacement surgery, as an important feature of AS, data on the epidemiology, nature of the disease and therapeutic strategies are scarce. We aimed to describe the epidemiology of clinical and radiological hip involvement and define the risk factors for the hip replacement surgery in AS patients. METHODS Data from 3 datasets were merged, including 847 Belgian (ASPECT database), 1405 Spanish (REGISPONSER database) and 466 Ibero-American (RESPONDIA database) AS patients. The ASPECT and REGISPONSER database (Dataset A) are used for exploratory analysis; the RESPONDIA database (Dataset B) is used for confirmative analysis. Factors associated with hip involvement and the hip replacement surgery were analysed. RESULTS Twenty four (REGISPONSER) to 36% (RESPONDIA) of AS patients under rheumatologists care presented clinical hip involvement, including the 5% (Dataset A) of AS patients who needed hip replacement surgery. Patients with hip involvement had significantly worse overall Bath Ankylosing Spondylitis Functional Index (BASFI) scores compared with patients without hip involvement (mean difference = 1.6, P < 0.001) (Dataset A, confirmed in B). Corrected for disease duration, patients with early disease onset, enthesial and axial disease needed most frequently hip replacement surgery (Dataset A, confirmed in B). CONCLUSION Hip involvement is commonly recognized by rheumatologists in AS patients, and involves about one out of the three to four patients with AS and is associated with impaired functioning reflected by higher overall BASFI scores. Early onset of disease, axial and enthesial disease are associated with the hip replacement surgery in AS.

Spinal Radiographic Changes in Ankylosing Spondylitis: Association with Clinical Characteristics and Functional Outcome

Objective. To determine which patients with ankylosing spondylitis (AS) have radiographic spinal damage and to investigate the relation between radiographic spinal changes and limitations in physical function. Methods. A cross-sectional nationwide study in Belgium of patients with AS under the care of a rheumatologist. The treating physician completed a questionnaire including clinical disease manifestations and laboratory findings (HLA-B27 and C-reactive protein), and classified spinal radiographs into 3 categories: (1) no AS-related spinal abnormalities; (2) syndesmophytes; and (3) spinal ankylosis. Patients completed the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI). Ordinal regressions were performed to quantify the relationship between clinical manifestations and spinal radiographic changes. Generalized linear models were computed to quantify relationships among clinical manifestations, radiographic spinal changes, and functioning (BASFI). Results. A total of 619 patients fulfilled modified New York criteria for definite AS and had evaluable radiographic data; 68% were male and disease duration was 17.5 (SD 12.2) years. Male sex, younger age at symptom onset, and hip involvement were associated with radiographic changes; but HLA-B27, peripheral arthritis, and extraarticular disease status (uveitis, psoriasis, and inflammatory bowel disease) were not. Older age, BASDAI, hip involvement, and spinal change contributed to BASFI; but sex, disease duration, peripheral arthritis, and extraarticular manifestations did not. Conclusion. Radiographic spinal changes in patients with AS are seen more often in men and those with hip involvement. BASFI status indicates the influence of radiographic changes and hip involvement, but does not reflect the presence of peripheral arthritis and does not differ between men and women.

Maintenance of biologic-free remission with naproxen or no treatment in patients with early, active axial spondyloarthritis: results from a 6-month, randomised, open-label follow-up study, INFAST Part 2

Objective To investigate whether biologic-free remission can be achieved in patients with early, active axial spondyloarthritis (SpA) who were in partial remission after 28 weeks of infliximab (IFX)+naproxen (NPX) or placebo (PBO)+NPX treatment and whether treatment with NPX was superior to no treatment to maintain disease control. Method Infliximab as First-Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial (INFAST) Part 1 was a double-blind, randomised, controlled trial in biologic-naïve patients with early, active, moderate-to-severe axial SpA treated with either IFX 5 mg/kg+NPX 1000 mg/d or PBO+NPX 1000 mg/d for 28 weeks. Patients achieving Assessment of SpondyloArthritis international Society (ASAS) partial remission at week 28 continued to Part 2 and were randomised (1:1) to NPX or no treatment until week 52. Treatment group differences in ASAS partial remission and other efficacy variables were assessed through week 52 with Fisher exact tests. Results At week 52, similar percentages of patients in the NPX group (47.5%, 19/40) and the no-treatment group (40.0%, 16/40) maintained partial remission, p=0.65. Median duration of partial remission was 23 weeks in the NPX group and 12.6 weeks in the no-treatment group (p=0.38). Mean Bath Ankylosing Spondylitis Disease Activity Index scores were low at week 28, the start of follow-up treatment (NPX, 0.7; no treatment, 0.6), and remained low at week 52 (NPX, 1.2; no treatment, 1.7). Conclusions In axial SpA patients who reached partial remission after treatment with either IFX+NPX or NPX alone, disease activity remained low, and about half of patients remained in remission during 6 months in which NPX was continued or all treatments were stopped.

Efficacy and safety of golimumab as add-on therapy to disease-modifying antirheumatic drugs: results of the GO-MORE study

Objectives To evaluate the efficacy and safety of subcutaneous golimumab as add-on therapy in patients with active rheumatoid arthritis (RA) despite disease-modifying antirheumatic drug (DMARD) treatment. To evaluate an intravenous plus subcutaneous (IV+SC) golimumab strategy in patients who had not attained remission. Methods GO-MORE was an open-label, multinational, prospective study in patients with active RA in typical clinical practice settings. In part 1, patients received add-on monthly 50-mg subcutaneous golimumab for 6 months. The percentage of patients with good/moderate European League Against Rheumatism (EULAR) 28-joint disease activity score (DAS28)–erythrocyte sedimentation rate (ESR) response was compared in patient subgroups with various concurrent or previous DMARD treatments. In part 2, patients with EULAR responses but not remission were randomly assigned to receive IV+SC or subcutaneous golimumab to month 12; DAS28–ESR remission was measured. Results 3366 patients were enrolled. At baseline of part 1, 3280 efficacy-evaluable patients had mean disease duration of 7.6 years and mean DAS28–ESR of 5.97 (SD=1.095). At month 6, 82.1% achieved good/moderate EULAR responses and 23.9% attained remission. When EULAR responses were analysed by the number of previously failed DMARD or the concomitant methotrexate dose, DMARD type, or corticosteroid use, no statistically significant differences were observed. Part 2 patients (N=490) who received IV+SC or subcutaneous golimumab achieved similar remission rates (∼25%). Adverse events were consistent with previous reports of golimumab and other tumour necrosis antagonists in this population. Conclusions Add-on monthly subcutaneous golimumab resulted in good/moderate EULAR response in most patients; 25% achieved remission after 6 more months of golimumab, but an IV+SC regimen provided no additional efficacy over the subcutaneous regimen.

Measuring joint involvement in polyarticular psoriatic arthritis: An introduction of alternatives†

To compare the reliability of 3 different simplified joint counts with the gold standard 66 swollen/68 tender joint count (JC66/68) for assessing clinical response in patients with polyarticular psoriatic arthritis (PsA).

ASDAS high disease activity versus BASDAI elevation in patients with ankylosing spondylitis as selection criterion for anti-TNF therapy

OBJECTIVE To investigate which of the 2 ankylosing spondylitis (AS) disease activity instruments identifies better those patients with characteristics that have been associated with positive response to anti-TNF therapy. METHODS Data from patients with AS in the REGISPONSER registry were analyzed. Patients were categorized by disease activity using 3 different selection criteria: elevated Bath Ankylosing Spondylitis Disease Activity Index criteria (BASDAI≥4), high Ankylosing Spondylitis Disease Activity Score (ASDAS≥2.1), or very high ASDAS (ASDAS≥3.5). To determine which criterion selects for patients most likely to respond to anti-TNF therapy, the groups of patients selected with each criterion were compared on five disease characteristics that are associated with good response to anti-TNF therapy: lower age, lower function score, less enthesitis, higher C-reactive protein (CRP), and HLA-B27-positive status. RESULTS 50.9%, 66.3%, and 24.9% of 1156 patients had elevated BASDAI, high ASDAS, or very high ASDAS, respectively. Compared to patients selected with elevated BASDAI, more patients selected with high ASDAS had characteristics associated with good response to anti-TNF therapy. Patients with very high ASDAS had higher CRP and were younger, but more frequently had enthesitis and had higher function scores when compared to those with elevated BASDAI. CONCLUSIONS Selection of AS patients with the ASDAS instrument results in patient sub-populations with different characteristics than those selected with the BASDAI instrument. Since some of these characteristics have been associated with response to anti-TNF therapy, further study should establish if the choice of selection instrument improves the outcome of therapy in the selected populations.

Patient and physician expectations of add-on treatment with golimumab for rheumatoid arthritis: relationships between expectations and clinical and quality of life outcomes.

Rheumatoid arthritis (RA) management involves improving clinical outcomes and quality of life (QOL). Golimumab is used as add‐on therapy for patients who have failed disease‐modifying antirheumatic drugs (DMARDs). This GO‐MORE subanalysis investigated relationships between patient and physician expectations and outcomes.