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ObjectiveThe Assessment of Spondyloarthritis international Society Health Index (ASAS HI) measures global functioning and health in patients with axial spondyloarthritis (axSpA) covering domains of physical, emotional, and social functioning. The main aim of this study was to investigate the sensitivity to change of ASAS HI in comparison with established variables of disease activity, function, and mental health.MethodsPatients with axSpA from the disease register RABBIT-SpA with follow-up time of at least 12 months and available ASAS HI questionnaires were included. Patients received questionnaires addressing disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score [ASDAS]), physical function (Bath Ankylosing Spondylitis Functional Index [BASFI]), mental health (5-item World Health Organization Well-Being Index [WHO-5]), and global functioning (ASAS HI). Standardized response means (SRMs) were calculated to compare the sensitivity to change of different variables.ResultsSix hundred and sixty-seven patients were included, 552 treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and 115 with conventional synthetic DMARDs and/or nonsteroidal antiinflammatory drugs (control group). Between baseline and month 12, the mean ASAS HI declined from 6.9 to 5.1 in the bDMARD group and from 5.9 to 5.6 in the conventionally treated group. In the bDMARD group, the SRM of ASAS HI was 0.52, compared to 0.59 for BASFI, 0.65 for WHO-5, 0.73 for BASDAI, and 0.90 for ASDAS. The following ASAS HI domains were most frequently affected: pain (78% agreed), maintaining body position (75%), and energy/drive (73%). In the patients receiving bDMARDs, there was an improvement in all items. In the control group, the largest improvement was seen in pain.ConclusionAs expected, ASDAS and BASDAI as disease activity scores showed high sensitivity to change, whereas changes in physical function (BASFI), mental health (WHO-5), and the broader concept of functioning and health (ASAS HI) were moderate.

Objective.In patients with early active axial spondyloarthritis (axSpA) with a disease duration of < 5 years, the longterm efficacy of 3 years of continuous etanercept (ETN) treatment was assessed.Methods.In a previously reported ESTHER trial, patients with axSpA were randomized to treatment with ETN (n = 40) versus sulfasalazine (SSZ; n = 36) in the first year. We analyzed the clinical, laboratory, and magnetic resonance imaging (MRI) response in the pooled dataset of patients (study population; n = 61), including patients with ankylosing spondylitis (AS, n = 31) and nonradiographic axSpA (nr-axSpA, n = 30) who were continuously treated with ETN for 3 consecutive years. Data were analyzed using the last observation carried forward and completer analysis.Results.In the entire group of patients in the study population (n = 61), the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 5.7 (± 1.3) at baseline to 2.6 (± 2.4) at Year 3. The Ankylosing Spondylitis Disease Activity Score (ASDAS) decreased from 3.4 (± 0.8) to 1.5 (± 1.0). Also, mean values for MRI spine and sacroiliac joint scores showed a significant decrease. Response rates in the nr-axSpA group were similar and at least as good compared to the AS group for all outcome measures. When comparing remission stages, we found that ASDAS inactive disease correlated better with C-reactive protein and MRI remission than with Assessment of SpondyloArthritis international Society partial remission.Conclusion.There was a consistent and sustained clinical response in patients with early axSpA treated with ETN over 3 years. ClinicalTrials.gov registration number NCT00844142.

The Spondyloarthritis Research and Therapy Network (SPARTAN), founded in 2003 to promote research, education, and treatment of ankylosing spondylitis (AS) and related forms of spondyloarthritis (SpA), held its 7th Annual Research and Education Meeting in July 2009 in Houston, Texas. Current controversies in SpA discussed during the meeting included an update on the epidemiology of AS, axial SpA, and inflammatory back pain; the adequacy of the mSASS to assess radiographic involvement; the helpfulness of magnetic resonance imaging in assessing disease progression; the reliability of metrology in assessing damage; and whether biologic agents alter the course of AS. Presentations also were made on psoriasis in the SCID mouse model; the challenges and opportunities of SpA in China; a discussion of the special needs in managing SpA in Ibero-America, and the SPARK Survey in Europe and North America.

OBJECTIVE: New bone formation of the spine is a typical feature of ankylosing spondylitis (AS). It is unknown whether new bone formation is part of a physiological repair process or a unique pathological entity of the disease. METHODS: We analyzed zygapophyseal joints from patients with AS and osteoarthritis (OA) undergoing spinal surgery for rigid hyperkyphosis (AS) or radiculopathy caused by severe OA. In 17 patients with AS, 11 with OA, and 5 controls we performed immunohistochemical analysis of osteoprotegerin (OPG), nuclear factor-κB ligand (RANKL), and osteocalcin (OC) expression in osteoblasts and determined the trabecular thickness in AS and OA patients and controls. Osteoclasts were detected by tartrate-resistant alkaline phosphatase (TRAP) staining. RESULTS: Trabecular thickness was significantly lower in patients with AS compared to OA (p = 0.01). The absolute number of CD56+ osteoblasts (p < 0.001) and OC+ (p = 0.002), OPG+ (p = 0.003), and RANKL+ osteoblasts (p = 0.03) in AS patients was also significantly lower than in OA patients. The percentages of OC+, OPG+, and RANKL+ osteoblasts did not differ between AS and OA (p > 0.05 in all cases). In controls, the percentages of OPG+ (p = 0.013) and OC+ (p = 0.034) but not RANKL+ (p > 0.05) osteoblasts were significantly lower compared to AS patients. The frequency of TRAP+ osteoclasts in AS patients was significantly lower compared to OA (p < 0.001), but higher compared to controls. CONCLUSION: Immunohistochemical analysis of zygapophyseal joints suggested that osteoblast activity is similar in AS and OA, indicating that new bone formation is possibly a physiological function of repair in both diseases.

OBJECTIVE: To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis (AS). METHODS: A 96-week open-label extension study, which followed a 12-week double-blind placebo-controlled trial, was designed to provide longterm efficacy and safety data, including radiographic outcomes, for patients treated with etanercept 25 mg twice weekly (NCT00421980). In all, 81 patients were enrolled (96% of the participants from the double-blind study). Key efficacy measures included improvement using the Assessment in Ankylosing Spondylitis 20% (ASAS20) criteria, the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) method. Paired t tests were used to test within-group changes from baseline. RESULTS: The percentage of responders, by ASAS20 criteria, remained relatively constant in patients who received etanercept during the 12-week double-blind study (60% at Week 0 and 83% at Week 96 of the open-label extension); more patients from the placebo group became responders after being switched to etanercept (23% and 74%, respectively). A similar trend was also observed using the ASAS40 and ASAS5/6 criteria, the BASFI, and the BASDAI. Most patients had no change from baseline in mSASSS values. Etanercept was well tolerated; the most frequent adverse events were injection site reactions (n = 30; 37.0%) and headache (n = 18; 22.2%), and the most frequent infections were upper respiratory tract infections (n = 43; 53.1%) and flu syndrome (n = 22; 27.2%). CONCLUSION: For 2 years, etanercept was clinically effective and well tolerated, with no unexpected safety findings.

OBJECTIVE: We evaluated the effectiveness and safety of adalimumab in a large cohort of patients with active ankylosing spondylitis (AS) and identified clinical predictors of good clinical response. METHODS: Patients with active AS [Bath AS Disease Activity Index (BASDAI) ≥4] received adalimumab 40 mg every other week in addition to their standard antirheumatic therapies in a multinational 12-week, open-label study. We used 3 definitions of good clinical response: 50% improvement in the BASDAI (BASDAI = 50), 40% improvement in the ASsessments of SpondyloArthritis International Society criteria (ASAS40), or ASAS partial remission. Response predictors were determined by logistic regression with backward elimination (selection level 5%). RESULTS: Of 1250 patients, 1159 (92.7%) completed 12 weeks of adalimumab treatment. At Week 12, 57.2% of patients achieved BASDAI 50, 53.7% achieved ASAS40, and 27.7% achieved ASAS partial remission. Important predictors of good clinical response (BASDAI 50, ASAS40, and partial remission) were younger age (p < 0.001), and greater C-reactive protein (CRP) concentration (p ≤ 0.001), HLA-B27 positivity (p ≤ 0.01), and tumor necrosis factor (TNF) antagonist naivety (p < 0.001). CONCLUSION: Adalimumab was effective in this large cohort of patients with AS, with more than half of patients achieving a BASDAI 50 or ASAS40 response and more than a quarter of patients reaching partial remission at Week 12.Younger age, greater CRP concentrations, HLA-B27 positivity, and TNF antagonist naivety were strongly associated with BASDAI 50, ASAS40, and partial remission responses. ClinicalTrials.gov identifier: NCT00478660.

OBJECTIVE: To create a core set of measurement concepts for use in the creation and maintenance of anti-tumor necrosis factor-α patient registries in ankylosing spondylitis (AS). METHODS: A Delphi-based approach was used to identify elements that best identify a patient's clinical state, disease progression, and potential drug-related toxicities. Decision-making was based on systematic literature reviews and clinical experience and expertise. RESULTS: A core set of measurement domains was defined including disease activity and physical function outcomes. Comparison with domains used in existing AS registries showed excellent agreement with current practice. CONCLUSION: This core set is a basis for data collection across AS populations.

OBJECTIVE: To analyze the safety and efficacy of the anti-tumor necrosis factor agent infliximab in patients with ankylosing spondylitis (AS) after discontinuation of longterm therapy over 1 year and readministration, using clinical and laboratory assessments including serum levels of antibodies to infliximab (ATI). METHODS: Altogether 42/43 patients with AS in a 3-year multicenter trial discontinued therapy after continuous treatment with infliximab (5 mg/kg/6 wks). Infliximab was only readministered in case of a clinical relapse [judged by Bath AS Disease Activity Index (BASDAI) and physician global assessment > 4]. ATI were measured at different timepoints. The primary outcome was safety, and efficacy outcomes were secondary. RESULTS: One patient dropped out after the eighth infusion after retreatment due to repeated local infections. ATI were detected in this patient only. No other relevant adverse events were observed. One patient remained in clinical remission without therapy for more than 1 year. The other 40 patients (97.6%) were reinfused because of clinical relapse. There was no correlation between ATI and clinical measures. BASDAI 50% responses were seen in 25 (63%) and partial remission in 12 (30%) patients. The mean (± SD) BASDAI score dropped from 6.0 ± 1.4 at the time of relapse to 2.6 ± 2.0, and the median C-reactive protein from 11.2 to 1.8 mg/l after 1 year (all p < 0.05). CONCLUSION: Readministration of infliximab after discontinuation of longterm treatment was generally safe and efficacious. Ongoing remission after discontinuation was rare. There was only one patient with relevant adverse events. ATI were detected only in this patient, but there was no correlation to clinical data. Formation of ATI seems to be rare after longterm infliximab therapy in AS.

OBJECTIVE:To investigate the expression of membrane glucocorticoid receptors (mGCR) on peripheral blood mononuclear cells (PBMC) in patients with ankylosing spondylitis (AS). METHODS: We used high sensitivity immunofluorescence with magnetofluorescent liposomes for the detection of mGCR on PBMC from patients with AS (n = 26) and healthy controls (n = 11). RESULTS: The frequency of mGCR+ monocytes and B lymphocytes was significantly higher in patients with AS than in controls (monocytes 12.5 ± 9.9% vs 4.8 ± 1.4%, B lymphocytes 8.7 ± 6.3% vs 4.4 ± 3.6%). We did not find mGCR on T lymphocytes. The frequency of mGCR+ cells did not correlate with variables of AS disease activity [C-reactive protein, erythrocyte sedimentation rate, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI 6, or numerical rating scales]. CONCLUSION: mGCR are upregulated in monocytes and B lymphocytes of patients with AS. This upregulation does not correlate with the humoral or overall disease activity. mGCR are not present on T lymphocytes. Our findings may be related to the limited benefit of low-dose and the efficacy of high-dose (intravenous pulse or intraarticular) glucocorticoid treatment in AS. Drugs binding selectively to mGCR may be a new therapeutic option for AS.

OBJECTIVE: To compare quality of life and treatment among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) treated by German rheumatologists. METHODS: Data for outpatients with PsA (n = 1863), RA (n = 9627), or AS (n = 1378) enrolled in the national database of the German collaborative arthritis centers in the year 2002 were analyzed. Among those with PsA, 2 subgroups with predominantly peripheral arthritis (n = 1612) and predominantly axial disease (n = 251) were distinguished. RESULTS: We found a high burden of illness in patients with PsA treated by rheumatologists. Among the 2 subgroups, those with axial PsA had worse outcomes (pain, function) than those with peripheral PsA. However, compared with RA and AS, physician ratings of disease activity and severity were lower in PsA. Concerning access to rheumatology care, there were similarities between AS and axial PsA, with very long disease duration at first visit (mean of about 6 yrs), versus RA and peripheral PsA, with shorter duration (1.6 and 2.5 yrs, respectively). A majority (84%) of patients with PsA were treated with disease modifying antirheumatic drugs. Thirty percent of the patients with PsA currently were under therapy with glucocorticoids, mainly (89%) with a dose < 7.5 mg. CONCLUSION: Patients with PsA seen in rheumatologic care have a burden of illness comparable to that of patients with RA or AS.

OBJECTIVE: To define the relationship between bone growth (syndesmophytes) and bone loss (osteoporosis) in ankylosing spondylitis (AS). METHODS: Bone mineral density (BMD) at the spine, hip, and radius was measured by dual-energy x-ray absorptiometry (DEXA), dual-energy quantitative computed tomography (DEQCT), and peripheral quantitative computed tomography (pQCT) in 103 patients with AS. Radiographs of the lumbar spine were used to detect syndesmophytes. Patients were divided in 3 groups according to disease duration. RESULTS: Osteopenia at the hip and spine was found by DEXA in 56% and 41%, respectively, of the patients with disease duration < 5 years (n = 27), with an additional 11% and 15% having osteoporosis. In patients with a longer disease duration, > 10 years (n = 28), 29% were osteoporotic at the hip and only 4% at the lumbar spine. In contrast, using spinal DEQCT, 59% of patients with early disease were found to be osteopenic; 36% of patients with long-standing disease were osteopenic and 18% were osteoporotic. More than half the patients (55%) had syndesmophytes (n = 55). With spinal DEQCT there were more patients with syndesmophytes (63%) in the group with reduced bone density than in the group without (45%). This was similar with DEXA measurements at the hip, where 31% compared to 14% had osteoporosis, respectively. Osteocalcin was elevated in 34% of patients, but was not associated with disease activity or BMD. CONCLUSION: The majority of patients with AS had reduced bone density. The method of bone density measurement is critical and should be different depending on disease duration. The finding that more patients with syndesmophytes had reduced bone density than those without suggests that bone growth and bone loss occur in parallel, and the role of inflammation in this process warrants further investigation.

OBJECTIVE:. Anti-tumor necrosis factor-a (TNF-α) therapy has been successfully used in patients with active ankylosing spondylitis (AS) and other subtypes of spondyloarthritis (SpA). Treatment options for patients with severe forms of undifferentiated spondyloarthritis (uSpA), a rather frequent SpA subset, are limited. In this open study we examined the efficacy of the TNF-α receptor fusion protein etanercept in patients with uSpA. METHODS: Ten patients classified to have uSpA according to modified European Spondylarthropathy Study Group criteria in a severe and active stage of disease were included in the study and received etanercept in a dosage of 25 mg two times a week for 12 weeks, followed by an observation period of 12 weeks. The following outcome variables were used: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Functional Index (BASFI), pain on a numerical rating scale, disability by the Funktionsfragebogen Hannover (FFbH), a validated questionnaire to assess functional disability, and quality of life (Medical Outcome Study Short Form-36, SF-36). The primary outcome variable was defined as ≥ 50% improvement of the BASDAI. RESULTS: Treatment with etanercept resulted in a ≥ 50% regression of disease activity in 60% (95% CI 31–83%) of the patients. The mean BASDAI at baseline of 6.1 (range 3.7–9.2) dropped significantly to 3.5 at Week 12 (0.8–8.7; p = 0.01). Function, spinal pain, peripheral arthritis, enthesitis, quality of life, and acute phase reactants improved similarly. The FFbH improved from 62.8% to 69.7%. After cessation of anti-TNF therapy, 4 out of 8 patients relapsed after an average of 4.5 weeks (range 3–6). Two patients went into longstanding remission. No severe adverse events or major infections were observed. CONCLUSION: This study strongly suggests that treatment with etanercept has short term efficacy in patients with active and severe uSpA. Since it is known that 30–50% of uSpA patients develop AS over time, it will be important to study whether this can be prevented by anti-TNF-α therapy.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) has been detected in sacroiliac joints of patients with spondyloarthropathies (SpA). Anti-TNF-a therapy has been efficacious in patients with active ankylosing spondylitis (AS) and psoriatic arthritis. Similar to these SpA subtypes, therapeutic options in undifferentiated SpA (uSpA) are also limited. We tested the efficacy of the monoclonal anti-TNF-alpha antibody infliximab in patients with active and severe uSpA in an open observation trial. METHODS: Six patients with uSpA were treated with 3 infusions of infliximab in a dosage of 3 (n = 3) or 5 mg/kg (n = 3) at Weeks 0, 2, and 6. The total observational period was 12 weeks. The Bath AS Disease Activity Index (BASDAI), the Functional Index (BASFI), pain on a visual analog scale, the Bath AS Metrology Index (BASMI), and quality of life (SF-36) were assessed before, during, and after therapy. RESULTS: Significant improvement at Day 1 after the first infusion lasting until Week 12 was reported by 5/6 patients. Improvement of > or = 50% in all activity, function, pain, and swollen joint scores was observed in the patients taking 5 mg/kg. The 3 mg/kg dose was less effective, resulting in > or = 15% improvement in outcome variables. Peripheral arthritis, enthesitis, and spinal symptoms improved equally. C-reactive protein dropped in 4 patients. Health related quality of life increased. No serious side effects or infections occurred. CONCLUSION: These observations suggest that anti-TNF-alpha therapy has significant short term efficacy in patients with severe uSpA.