Bath Active Ankylosing Spondylitis Disease Activity Research Articles

Effectiveness of a supervised group exercise therapy based on the biopsychosocial model introduced simultaneously with anti-TNF therapy in anti-TNF-naive patients with active ankylosing spondylitis.

This study aimed to investigate the effectiveness of a supervised group exercise therapy based on the biopsychosocial model introduced simultaneously with antitumor necrosis factor (TNF) therapy in anti-TNF-naive patients with active ankylosing spondylitis (AS). Forty-eight patients were divided into two groups: the control group (CG; n = 36) received only anti-TNF therapy, and the study group (SG; n = 12) received the supervised exercise therapy based on the biopsychosocial model in addition to anti-TNF therapy. The measurements of disease activity and functionality were evaluated by The Bath AS Disease Activity Index (BASDAI) and The Bath AS Functional Index (BASFI) respectively. Other outcome measures evaluated biopsychosocial status, emotional state, spinal mobility, pain, fatigue, sleep, and quality of life. All measurements were applied to both groups at baseline and repeated 12 weeks later. BASDAI and BASFI analyses revealed significant differences between groups in favor of the SG (p < 0.05). At the end of the 12 weeks, the results showed that there were additional improvements in all outcome measurement parameters in the SG compared to the CG. The supervised group exercise therapy based on the biopsychosocial model introduced simultaneously with anti-TNF therapy is more effective than only anti-TNF therapy in anti-TNF-naive patients with active AS.

Effect of anti-tumor necrosis factor α treatment on radiographic progression in patient with ankylosing spondylitis: A systematic review and meta-analysis

Background: Efficacy of anti-tumor necrosis factor (anti-TNF)α treatment in patient with active ankylosing spondylitis (AS) had been proved by many clinical studies. Inflammation and new bone formation in spine were two pivotal aspects in AS. TNF α inhibitor could eliminate inflammation including clinical and laboratory inflammatory manifestation. Paradoxical results whether TNF α antagonist could delay radiographic progression in AS were often been reported simultaneously.Objectives: To review the literature about the effect of TNF α inhibitor on radiographic progression and disease activity in patient with AS.Methods: We conducted a comprehensive search including Medline, EMBASE and the Cochrane Library from 1 January 2000 to 15 August 2017. Two reviewers independently supplemented with hand searching for the reference lists of inclusion. All trials focusing on radiographic progression or disease activity in patients with AS treated with anti-TNF α agents. Primary outcomes were modified Stokes AS Spinal Score (mSASSS), as well as Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI). Two reviewers independently selected studies and analyzed data. Methodological quality was assessed using the Newcastle-Ottawa scale (NOS). We pooled effects recorded on different scales as Standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models.Results: We included 14 studies of low to moderate risk of bias with 3,186 patients, compared with control group, there was no effect of mSASSS changes (SMD = –0.12, 95% CI: –1.17–0.93, p value = .82, I2 = 95%) and follow-up (SMD = 0.03, 95% CI: 0.21–0.26, p value = .82, I2 = 36%) estimation in anti-TNF α group. However anti-TNF α agent treatment led to remarkable improvements on both Bath AS disease activity index (BASDAI) (SMD = 1.06, 95% CI: 0.22–1.89, p value = .01, I2 = 96%) and Bath AS functional index (BASFI) (SMD = 0.93, 95% CI: 0.24–1.92, p value = .01, I2 = 97%) scores at 12 weeks.Conclusion: Our meta-analysis found no significant effect on delaying radiographic progression in AS treated with TNF α inhibitor, although TNF α inhibitor could do improve significantly disease activity and physical function in AS.

Inflammatory back pain in psoriatic arthritis is significantly more responsive to corticosteroids compared to back pain in ankylosing spondylitis: a prospective, open-labelled, controlled pilot study

BackgroundThe efficacy of corticosteroids in patients with psoriatic arthritis (PsA) and inflammatory back pain has not been studied to date. In this controlled trial, we aimed to investigate the comparative performance of corticosteroids in patients with active axial-PsA (AxPsA) versus those with active ankylosing spondylitis (AS).MethodsPatients with AxPsA and AS (naïve to biologic therapies), who not only had clinically active disease, but also had bone marrow oedema on magnetic resonance imaging of the sacroiliac joints, were recruited. Clinically active disease was defined as inflammatory back pain (fulfilling Assessment of Spondyloarthritis International Society (ASAS) expert criteria), with spinal pain score (numerical rating scale 0–10) ≥4 and Bath AS Disease Activity Index (BASDAI) score ≥4 despite taking nonsteroidal anti-inflammatory drugs. Moreover, we recruited a control group of patients with non-inflammatory lower back pain. All patients received a single, intra-muscular dose of depot corticosteroid injection (triamcinolone acetonide 80 mg) at baseline. The intra-muscular corticosteroid option was used to overcome any drug compliance issues. Clinical outcome assessments were made at the following time points: baseline, week 2, and week 4. The primary efficacy end point was mean change in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 2. Key secondary outcomes were mean change in the BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI) and Ankylosing Spondylitis Quality of Life (ASQoL) at weeks 2 and 4.ResultsIn total, 40 patients were recruited (15 with AxPsA, 15 with AS, and 10 controls). At week 2 following corticosteroid treatment, patients with AxPsA had significantly greater improvement in the mean ASDAS compared to patients with AS (1.43 ± 0.39 vs. 1.03 ± 0.30, p = 0.004), and also when compared to controls (p < 0.001). At week-4, similar significant trend of ASDAS improvement was seen among AxPsA patients compared to AS patients (1.09 ± 0.32 vs. 0.77 ± 0.27, p = 0.007) and controls (p < 0.001). Similarly, the mean BASDAI, visual analogue scale spinal pain score, ASQoL and BASFI improved significantly among patients with AxPsA compared to patients with AS and controls at week 2 (p < 0.05), with this trend also largely maintained at week 4.ConclusionsAxial inflammation in patients with PsA responds significantly better to corticosteroids than in patients with AS. This furthers the argument and adds to the growing evidence that AxPsA and AS are distinct entities.

The safety and efficacy of golimumab in treatment of 25 patients with active ankylosing spondylitis

Objective: To evaluate the efficacy and safety of golimumab in patients with active ankylosing spondylitis (AS). Methods: This was a randomized, double-blind, placebo-controlled trial. The subjects were randomized to receive either golimumab 50mg subcutaneously or placebo every 4 weeks. Patients in both groups received golimumab 50mg from week 24 to week 48. The primary endpoint was the proportion of at least 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) at week 14. The secondary endpoints included at least 40% improvement in the Assessment of Spondyloarthritis International Society (ASAS40), ASAS partial-remission, Bath AS functional index, Bath AS disease activity index, Bath AS metrology index, enthesitis index and Jenkins sleep evaluation questionnaire. Results: A total of 25 subjects were included in this study, 13 with golimumab and 12 with placebo. At Week 14, 6(46.2%) subjects achieved ASAS20 in golimumab group and 2(16.7%) in placebo group. Significant improvements of other efficacy endpoints were also found in golimumab group. Golimumab was safe and well to lerated. Most of the adverse events were slightly impaired liver function, where as elevated aspartate aminotransferase and/or alanine aminotransferase returned to normal without drug with drawal. Conclusion: Golimumab improves AS activity, clinical symptoms and sleep disturbance in patients with active AS with good safety and tolerability.

Hybrid 18F-labeled Fluoride Positron Emission Tomography/Magnetic Resonance (MR) Imaging of the Sacroiliac Joints and the Spine in Patients with Axial Spondyloarthritis: A Pilot Study Exploring the Link of MR Bone Pathologies and Increased Osteoblastic Activity.

The biologically active molecule used in positron emission tomography (PET) for depiction of osteoblastic activity is 18F-labeled fluoride (18F-F). We examined whether inflammatory or chronic changes on magnetic resonance imaging (MRI) in the sacroiliac joints (SIJ) and the spines of patients with active ankylosing spondylitis (AS) are linked to osteoblastic activity, assessed by PET/MRI. Thirteen patients with AS (mean age 37.8 ± 11.4 yrs, Bath AS Disease Activity Index > 4, no anti-TNF treatment) underwent 3-Tesla whole-spine and SIJ PET/MRI. Two independent readers recorded pathologic changes related to vertebral (VQ) or SIJ quadrants (SQ). Final scores were based on reader agreement. A total of 104 SQ and 1196 VQ were examined. In SIJ, bone marrow edema (BME) was seen in 44.2%, fat deposition (FD) in 42.3%, and 18F-F in 46.2% SQ. BME alone was associated with 18F-F in 78.6% and FD alone in only 7.7% SQ, while the combination BME/FD was associated with 18F-F in 72.2% SQ. Erosions, sclerosis, and ankylosis alone were rarely associated with 18F-F. In the spine, BME alone was seen in 9.9%, FD in 18.2%, and 18F-F in 5.4% VQ. BME alone was associated with 18F-F in 14.3% and FD alone in 8.7% VQ, while the combination BME/FD was associated with 18F-F in 40.6% VQ. In this study of hybrid 18F-F PET/MRI of patients with active AS, we show that BME rather than chronic changes is associated with osteoblastic activity, while the combination of BME and FD showed the highest 18F-F uptake. The use of PET/MRI in prediction of future syndesmophyte formation in AS needs further exploration in prospective studies.

Predictors of Clinical Remission under Anti-tumor Necrosis Factor Treatment in Patients with Ankylosing Spondylitis: Pooled Analysis from Large Randomized Clinical Trials.

Investigate the role and relation of disease duration of different factors for achieving clinical remission with anti-tumor necrosis factor (TNF) treatment in patients with active ankylosing spondylitis (AS). Data pooled from 4 large (n = 1281) clinical trials were used to compare disease duration subgroups for placebo or sulfasalazine (SSZ) versus etanercept (ETN), which, in turn, were analyzed by age of diagnosis ≤ 40 versus > 40 years, HLA-B27 status, and baseline C-reactive protein (CRP) ≤ upper limit of normal (ULN) versus > ULN using chi-square tests, and ANCOVA. The primary efficacy measure was Assessments of SpondyloArthritis international Society (ASAS) partial remission (PR) after 12 weeks of treatment. Also analyzed were Bath AS Disease Activity Index and Functional Index, AS Disease Activity Scores, and ASAS response rates. Overall, a larger percentage of patients achieved ASAS-PR with ETN versus SSZ or placebo. More patients with ≤ 2-year disease duration treated with ETN experienced partial remission (34%) versus longer disease duration (30%, 27%, and 22% for > 2-5, > 5-10, and > 10 yrs, respectively; all p < 0.05). In the subgroup of patients with both disease duration ≤ 2 years and aged ≤ 40 years at diagnosis, the treatment response was even more pronounced. Similar results were seen in HLA-B27-positive patients in the disease duration ≤ 2-year subgroup. Overall, patients with high CRP at baseline had better treatment responses compared with patients with normal CRP. Treatment response under anti-TNF treatment with ETN at 12 weeks was greatest among patients with disease duration ≤ 2 years and even more pronounced in subgroups of patients ≤ 40 years old or HLA-B27-positive at diagnosis.

Golimumab administered subcutaneously every 4 weeks in ankylosing spondylitis: 5-year results of the GO-RAISE study

ObjectiveAssess golimumab efficacy/safety through 5 years in patients with active ankylosing spondylitis (AS).Methods356 patients with AS were randomly assigned to placebo, golimumab 50 mg or 100 mg every 4 weeks....

Efficacy of oral prednisolone in active ankylosing spondylitis: results of a double-blind, randomised, placebo-controlled short-term trial

BackgroundThe efficacy of oral prednisolone in patients with active ankylosing spondylitis (AS) has not been studied to date.MethodsIn this double-blind, randomised, placebo-controlled trial, patients with AS with active disease despite...

Female patients with ankylosing spondylitis: analysis of the impact of gender across treatment studies

ObjectivesTo examine the impact (if any) of gender on the clinical, functional and patient-reported outcomes of treatment using data pooled from four controlled clinical trials.MethodsStudy data were pooled from four...

Beneficial effects of tripterygium glycosides tablet on biomarkers in patients with ankylosing spondylitis.

The aim of the current study was to explore the effects and possible mechanisms of tripterygium glycosides tablet (TGT) in the treatment of active ankylosing spondylitis (AS). Thirty-six patients with active AS were given a 20 mg TGT treatment three times per day for 12 weeks, and 21 unrelated healthy controls were recruited as the control group. Efficacy measures included the Bath AS disease activity index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) prior and subsequent to TGT treatment. Serum dickkopf homolog 1 (DKK1) and interleukin-17 (IL-17) levels before and after TGT treatment were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA assay. The levels of several serum biomarkers were determined by ELISA, including receptor activator of nuclear factor κ-B ligand (RANKL), osteoprotegerin (OPG), bone alkaline phosphatase (BAP), bone morphogenetic protein-2 (BMP-2), matrix metalloproteinase-3 (MMP-3), cross-linked telopeptide of type II collagen (CTX-II), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2). After 12 weeks of TGT treatment, the BASDAI score of the patients was significantly reduced (P<0.05), their levels of ESR and CRP were significantly reduced to a normal level (P<0.05, P<0.05), RT-PCR and ELISA showed a significant increase in the level of DKK1 expression (P<0.05) and a significant decreased IL-17 expression (P<0.05), there was a significant increase in the expression of OPG, BAP and BMP-2 (P<0.01, P<0.01, P<0.01) and a significant reduction in the expression levels of RANKL, CTX-II. MMP-3, PGE2, and VEGF (P<0.01, P<0.01, P<0.01, P<0.05, P<0.01) compared with those of the controls. TGT is effective at improving the signs and symptoms of patients with AS through the regulation of serum biomarkers, and the mechanisms may be associated with the anti-inflammatory effect, inhibition of new bone formation and potential bone-protective effects.

Golimumab reduces sleep disturbance in patients with active ankylosing spondylitis: Results from a randomized, placebo‐controlled trial

To evaluate the effect of golimumab on sleep disturbance in patients with active ankylosing spondylitis (AS). Golimumab was studied in a multicenter, randomized, placebo-controlled study (GO-RAISE). At baseline, 356 patients were randomly assigned in a 1.8:1.8:1 ratio to subcutaneous golimumab 50 mg, 100 mg, or placebo every 4 weeks. Sleep disturbance was assessed using the Jenkins Sleep Evaluation Questionnaire (JSEQ), which was administered at baseline, week 14, and week 24. Treatment effect was evaluated using analysis of variance on the van der Waerden normal scores. Median JSEQ scores at baseline were 9.0 in the placebo group, 10.0 in the 50-mg group, and 11.0 in the 100-mg group, indicating moderate to severe sleep disturbance. Patients who received golimumab showed significantly greater median improvement from baseline in JSEQ scores compared with placebo at week 14 (-3.0 versus 0.0; P < 0.001) and week 24 (-3.0 versus -1.0; P < 0.001). Changes from baseline in JSEQ scores significantly correlated with changes from baseline in Short Form 36 summary scores, Bath AS Functional Index scores, total back pain, night back pain, and Bath AS Disease Activity Index scores. Multiple regression analyses indicated that improvement in the night back pain score was the most consistent predictor of change in JSEQ score or reduction in sleep disturbance. Patients with active AS showed significant sleep disturbance at baseline due to underlying pain associated with AS. Treatment with subcutaneous golimumab every 4 weeks significantly reduced sleep disturbance and improved health-related quality of life.

Effectiveness, Safety, and Predictors of Good Clinical Response in 1250 Patients Treated with Adalimumab for Active Ankylosing Spondylitis

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. Patients with active AS [Bath AS Disease Activity Index (BASDAI)>or=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%). 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<or=0.001), HLA-B27 positivity (p<or=0.01), and tumor necrosis factor (TNF) antagonist naivety (p<0.001). 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.

Physical function, disease activity, and health-related quality-of-life outcomes after 3 years of adalimumab treatment in patients with ankylosing spondylitis

IntroductionWe evaluated the three-year impact of adalimumab on patient-reported physical function and health-related quality-of-life (HRQOL) outcomes in patients with active ankylosing spondylitis (AS).MethodsThe Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS (ATLAS) is an ongoing five-year study that included an initial 24-week, randomized, placebo-controlled, double-blind period, followed by open-label extension treatment with adalimumab. Clinical and HRQOL data collected for up to three years from ATLAS were used for these analyses. Patients were randomized to receive adalimumab 40 mg or placebo by subcutaneous injection every other week. Physical function was assessed by the Bath AS Functional Index (BASFI), as well as by the Short Form 36 (SF-36) Health Survey Physical Component Summary (PCS) and Physical Function subscale scores. HRQOL was assessed using the AS Quality of Life (ASQOL) questionnaire. Disease activity was assessed by the Bath AS Disease Activity Index (BASDAI).ResultsOf 315 patients enrolled in ATLAS, 288 (91%) participated in an open-label adalimumab treatment extension and 82% provided three-year outcome data. During the 24-week double-blind phase, adalimumab-treated patients experienced significant improvement compared with placebo-treated patients in the BASDAI (P < 0.001), BASFI (P < 0.001), ASQOL (P < 0.001), and both the SF-36 PCS (P < 0.001) and Physical Function subscale (P < 0.001) scores, but not the SF-36 Mental Component Summary score (P = 0.181) and Mental Health subscale scores (P = 0.551). Mean changes from baseline through three years of adalimumab treatment were statistically significant for the BASDAI (change score: -3.9, P < 0.001), BASFI (change score: -29.6, P < 0.001), SF-36 PCS (change score: 11.6, P < 0.001), and Physical Function (change score: 23.3, P < 0.001). Comparable results were observed for the other SF-36 scores and for the ASQOL (all P < 0.001).ConclusionsAdalimumab significantly improved disease activity, patient-reported physical function, and HRQOL. These benefits were maintained over three years of treatment in patients with AS.Trial registrationClinicalTrials.gov NCT00085644.

Pro-inflammatory effect of leptin on peripheral blood mononuclear cells of patients with ankylosing spondylitis

Objectives This study was performed to investigate whether leptin mRNA expression is increased from peripheral blood mononuclear cells (PBMCs) of patients with active ankylosing spondylitis (AS) and whether it stimulates the production of pro-inflammatory cytokines. Methods Twenty patients with active AS were enrolled and their Bath AS disease activity index (BASDAI) and levels of acute phase reactants were measured. Leptin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α mRNA expressions and their protein productions were determined in PBMCs of patients with AS using semi-quantitative reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. Then, the results were compared with those from 20 healthy controls, as were clinical and laboratory parameters reflecting disease activity. The changes of pro-inflammatory cytokine productions from PBMCs in response to leptin stimulation were also determined. Results Leptin, IL-6 and TNF-α mRNA expressions of PMBCs from patients with AS were significantly higher than controls. Similar significances were also found in the measurements for leptin and cytokine levels of supernatants, and leptin levels correlated well with IL-6 expression ( r = 0.871, p < 0.001) and BASDAI ( r = 0.691, p < 0.001) in patients with AS. Stimulation of PBMCs by exogenous leptin significantly increased the production of IL-6 and TNF-α in PBMCs from patients with AS in a dose-dependent fashion and these increases were much exacerbated compared to controls. Conclusion Our results shows that leptin production is increased and its stimulation of PBMCs significantly increased the production of pro-inflammatory cytokines in patients with active AS, suggesting its pro-inflammatory effect in pathogenesis of AS.

Clinical evaluation and radiological observation of recombinant human tumor necrosis factor receptor-Fc fusion protein in treatment of active ankylosing spondylitis

To evaluate the efficacy of recombinant human tumor necrosis factor receptor-Fc fusion protein (rh TNFR:Fc) in the treatment of active ankylosing spondylitis (AS). 68 patients with active AS underwent subcutaneous injection of rh TNFR: Fc 25 mg twice a week for 24 weeks. The following indexes were observed: improvement of at least 20% of reported symptoms, based on the multicomponent Assessments in AS (ASAS) response criteria (ASAS 20) at weeks 2, 6, 12 and 24, ASAS 50 and ASAS 70 responses, and improved scores on individual components of ASAS, including Bath AS disease activity index (BASDAI), acute phase reactants, and Bath AS metrology index (BASMI). And the X-ray images of patient's pelvis at weeks 0, 12, and 24 were graded based on BASRI. After treatment of rh TNFR:Fc the primary and secondary efficacy end points of the 68 patients were all improved compared with the baseline values. During the process of treatment, the number of patients with the efficacy achieving ASAS20 was gradually rising: 44 cases (64.7%) at week 12 and 58 (85.0%) at week 24. The efficacy of 41 cases (60.3% ) reached ASAS50 and that of 34 cases reached ASAS70 at week 24. Other efficacy end points also reflected the similar effect and were improved significantly compared with the baseline values at different time points ( all P < 0.01). BASRI showed that the radiological improvement of sacroiliac joint was not significant (P > 0.05) and that the radiological improvement of hip was not obvious at week 12 (P > 0.05) but significant at week 24 (P < 0.05). rh TNFR:Fc rapidly improves the signs and symptoms of active AS.

Persistent clinical response to the anti-TNF-α antibody infliximab in patients with ankylosing spondylitis over 3 years

Infliximab, a monoclonal antibody against tumour necrosis factor alpha (TNF-alpha), is approved in Europe for the treatment of patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy. This report provides analyses from a 3-yr extension study, as a follow-up to both the 1- and 2-yr open label extensions of the original 3-month randomized controlled trial of infliximab in patients with AS. Of the 49 patients with AS who completed the second year of the study, 46 continued treatment with infliximab 5 mg/kg every 6 weeks up to week 156. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index, the Bath AS Metrology Index, patient's and physician's global assessments, quality of life (Short Form-36), C-reactive protein (CRP) and erythrocyte sedimentation rate were assessed throughout the study period. The improvement of signs and symptoms observed in the majority of the patients during the first and second year was sustained throughout the third year of the study. Forty-three patients (62% of the 69 patients enrolled at baseline and 93% of the patients who started the third year) completed week 156. In the intention-to-treat analysis, an ASAS '5 out of 6' and ASAS 40% response was seen by 46% and 50% of the patients, respectively. The scores for other efficacy assessments were similar to the values observed at weeks 54 and 102. Median CRP levels remained low (1.5 mg/l at week 156). There were no relevant side-effects and no discontinuation because of drug-related adverse events during the third year of the study. Patients with AS receiving infliximab for 3 yr showed a durable clinical response without loss of efficacy. Long-term infliximab treatment was well tolerated by patients in this study.