Exploring complement biomarkers in suspected axial spondyloarthritis.

OBJECTIVES: To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals. METHODS: Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg). RESULTS: Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity. CONCLUSIONS: Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.

Proton Pump Inhibitor Use and Bone Health in Patients With Rheumatic Diseases: A Cross-Sectional Study.

OBJECTIVE: To assess the effect of proton pump inhibitor (PPI) use on bone mineral density (BMD) and bone microarchitecture as measured by the trabecular bone score (TBS) in patients with inflammatory rheumatic and musculoskeletal diseases (iRMDs). METHODS: Cross-sectional data from a prospective single-center cohort (2015 to 2022) of patients with iRMDs were used to evaluate 3 co-primary outcomes: BMD of the left femoral neck and the lumbar spine (as T-scores) and the TBS. Inverse probability weighting adjusted for numerous confounders including age, sex, body mass index, current and cumulative glucocorticoid (GC) dose, C-reactive protein levels, disability, and others. Analyses were based on general linear models, following a prespecified statistical analysis plan. RESULTS: The study included 1495 patients (75% women; mean age, 62.6±13.1 years; 49% and 63% with regular PPI and GC use, respectively). The PPI users had lower BMD at both spine (adjusted contrast -0.25; 95% CI, -0.47 to -0.04; P=.02) and femoral neck (-0.17 [-0.35 to 0.01]; P=.07). Differences between PPI users and nonusers were statistically significant only in patients concurrently using GCs at more than 7.5 mg/d prednisone equivalent. The TBS was similar in PPI users and nonusers (adjusted contrast, 0.00 [-0.04 to 0.04]; P=.97). CONCLUSION: Our results suggest that PPIs lead to a loss of BMD rather than an impairment of bone microarchitecture in patients with iRMDs. The negative association between PPI use and BMD appears to be dependent on concurrent GC use. Clinicians should carefully review the indication for PPI use in patients with iRMDs, especially in those receiving higher dose GCs.

Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial.

OBJECTIVES: The study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on radiographic spinal progression in patients with radiographic axial spondyloarthritis (r-axSpA) over 2 years. METHODS: R-axSpA patients, having risk factors for radiographic progression (high disease activity plus C reactive protein >5 mg/L and/or ≥1 syndesmophyte(s)), underwent a 12-week run-in phase with GOL 50 mg every 4 weeks. In the core phase (96 weeks), only patients with a good clinical response at week 12 were randomised (1:1) to GOL+CEL 200 mg two times per day (combination therapy) or GOL monotherapy. The primary endpoint was radiographic progression assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change at week 108 in the intent-to-treat population. RESULTS: A total of 128 patients were enrolled in the run-in phase; and 109 patients were randomised at week 12 to monotherapy (n=55) or combination therapy (n=54). At week 108, 97 (52 vs 45) patients completed the study. The change in mSASSS at week 108 was 1.7 (95% CI 0.8 to 2.6) in the monotherapy vs 1.1 (95% CI 0.4 to 1.8) in the combination therapy groups (p=0.79). New syndesmophytes occurred in 25% of patients in the monotherapy vs 11% of patients in the combination therapy groups (p=0.12). During the study, no significant differences in adverse events and serious adverse events were observed between the groups. CONCLUSIONS: Combination therapy with GOL+CEL did not demonstrate statistically significant superiority over GOL monotherapy in retarding radiographic spinal progression over 2 years in r-axSpA.

Sex and age do not modify the association between glucocorticoids and bone mineral density in patients with rheumatoid arthritis: a cross-sectional study.

BACKGROUND: It is unclear whether sex or age modify the association of glucocorticoid (GC) use with reduced bone mineral density (BMD) in patients with rheumatoid arthritis (RA). METHODS: We studied cross-sectional data of RA patients with current or previous GC treatment in a single center cohort study (Rh-GIOP cohort). Our primary outcome was the minimum T-score (measured by DXA) of either lumbar spine, total femur, or femoral neck. Current GC dose was the main exposure; cumulative GC dose and cumulative duration of GC use were also assessed. Following a predefined statistical analysis plan, linear regression analyses with adjustment for confounders assessed whether the association of GC use with BMD was modified by sex (men versus women) or age (≥ 65 versus < 65 years). RESULTS: Four hundred eighty-three patients with RA (mean age 64 ± 12 years, 80% women) were included. 33% were not currently taking GCs, 32% were treated with a dose of 5 mg/d prednisone equivalent and 11% with more than 7.5 mg/d. 23% of patients had osteoporosis by DXA (minimum T-score ≤ -2.5). The slope, i.e., the association between changes in minimum T-scores with 1 mg/d change in current GC dose, was similar in men and women (-0.07 and -0.04, respectively; difference -0.03 [-0.11 to 0.04]; p for interaction = 0.41). Slopes were also similar for elderly and non-elderly patients (-0.03 and -0.04, respectively; difference -0.01 [-0.06 to 0.05]; p for interaction = 0.77). Using cumulative dose and duration of use as exposures did not lead to substantial changes of these results. CONCLUSIONS: In our sample, the association of GC use with reduced BMD in RA was not modified by sex or age.

No association between methotrexate and impaired bone mineral density in a cohort of patients with polymyalgia rheumatica, giant cell arteritis, granulomatosis with polyangiitis and other vasculitides-a cross-sectional analysis with dose-response analyses.

OBJECTIVE: To investigate whether methotrexate (MTX) use is associated with bone mineral density (BMD) in patients with polymyalgia rheumatica (PMR) and various forms of vasculitis. METHODS: Rh-GIOP is a cohort study designed to evaluate bone health in patients with inflammatory rheumatic diseases. This cross-sectional analysis assessed the baseline visits of all patients with PMR or any kind of vasculitis. Following univariable analysis, multivariable linear regression analysis was performed. The lowest T-score of either the lumbar spine or the femur was chosen as the dependent variable to examine the relationship between MTX use and BMD. These analyses were adjusted for a variety of potential confounders, including age, sex, and glucocorticoid (GC) intake. RESULTS: Of 198 patients with PMR or vasculitis, 10 patients were excluded for very high GC dose (n = 6) or short disease duration (n = 4). The remaining 188 patients had the following diseases: PMR 37.2%, giant cell arteritis 25.0%, granulomatosis with polyangiitis 16.5%, followed by rarer diseases. The mean age was 68.0 ± 11.1 years, mean disease duration was 5.58 ± 6.39 years, and 19.7% had osteoporosis by dual x-ray absorptiometry (T-score ≤ -2.5). 23.4% were taking MTX at baseline with a mean dose of 13.2 mg/week (median: 15 mg/week). 38.6% of those used a subcutaneous preparation. MTX users had similar BMD compared to non-users (minimum T-scores -1.70 (± 0.86) versus -1.75 (± 0.91), respectively; p = 0.75). There was no statistically significant dose-response relationship: neither current nor cumulative dose were associated with BMD in unadjusted or adjusted models (current dose: slope -0.02; -0.14 to 0.09; p = 0.69; cumulative dose: slope -0.12; -0.28 to 0.05; p = 0.15). CONCLUSION: In the Rh-GIOP cohort, MTX is used in about a quarter of patients with PMR or vasculitis. It is not associated with BMD levels.

Evaluation of the Disease Activity index for PSoriatic Arthritis (DAPSA) with a quick quantitative C reactive protein assay (Q-DAPSA) in patients with psoriatic arthritis: a prospective multicentre cross-sectional study.

OBJECTIVES: This study aimed to evaluate the Disease Activity index for PSoriatic Arthritis (DAPSA) based on a quick quantitative C reactive protein (qCRP) assay (Q-DAPSA) in a multicentre, prospective, cross-sectional study in patients with psoriatic arthritis (PsA). METHODS: The assessment of prospectively recruited study patients included joint examination and patient reported outcome (PRO) measures (patient global assessment, patient pain assessment). Following, the DAPSA based on a routine laboratory CRP measurement, Q-DAPSA and clinical DAPSA (cDAPSA) were calculated. Cross-tabulations and weighted Cohen's kappa were performed to analyse the agreement of disease activity categories. Bland-Altman plots and intraclass correlation coefficients were used to determine the agreement of numerical values regarding CRP and qCRP as well as different disease activity scores. RESULTS: Altogether, 104 patients with PsA could be included in the statistical analysis. With Q-DAPSA, 102 of 104 (98.1%) patients achieved identical disease activity categories in comparison to DAPSA with a weighted Cohen's kappa of 0.980 (95% CI: 0.952 to 1.000). The agreement between DAPSA and cDAPSA was slightly lower with identical disease activity categories seen in 97 of 104 (93.3%) of patients and with a weighted Cohen's kappa of 0.932 (95% CI 0.885 to 0.980). CONCLUSIONS: The Q-DAPSA showed an almost perfect agreement with the conventional DAPSA regarding identical disease activity categories. Thus, the Q-DAPSA can be used as a timely available disease activity score in patients with PsA with the additional benefit of CRP involvement. Consequently, the Q-DAPSA could facilitate the implementation of the treat-to-target concept in clinical routine and clinical trials.

Validation of the Simplified Disease Activity Index (SDAI) with a quick quantitative C-reactive protein assay (SDAI-Q) in patients with rheumatoid arthritis: a prospective multicenter cross-sectional study.

Objectives: The Simplified Disease Activity Index (SDAI) is a recommended composite score for assessing the remission status in patients with rheumatoid arthritis (RA). However, determination of C-reactive protein (CRP) levels takes several hours and sometimes days and limits the use of the SDAI in the clinical setting. The aim of this study was to validate the SDAI using a quick quantitative C-reactive protein (qCRP) assay (as SDAI-Q) in RA patients. Design: This is a multicenter, prospective, cross-sectional pilot study in RA patients. Methods: Adult patients (⩾18 years) with a clinical diagnosis of RA were recruited between January 2020 and September 2020 from five rheumatologic centers located in Berlin, Germany. SDAI, SDAI-Q, Clinical Disease Activity Index (CDAI), and DAS28 scores comprising CRP, qCRP, or erythrocyte sedimentation rate (ESR) were calculated. The agreement of disease activity categories was analyzed using cross tabulations and weighted Cohen's kappa. The agreement of numerical values was analyzed with Bland-Altman plots and intraclass correlation coefficients (ICCs). Results: Overall, 100 RA patients were included in the statistical analysis. The mean value of qCRP (7.89 ± 16.98 mg/l) was slightly higher than that of routine laboratory CRP (6.97 ± 15.02 mg/l). Comparing SDAI and SDAI-Q, all patients were assigned to identical disease activity categories. Agreement of disease activity categories by CDAI and SDAI/SDAI-Q was observed in 93% with a weighted Cohen's kappa of 0.929 (95% confidence interval (CI) = 0.878; 0.981). Conclusion: The SDAI-Q showed an absolute agreement regarding the assignment of disease activity categories in comparison with the conventional SDAI. Therefore, the SDAI-Q may facilitate the application of a treat-to-target concept in clinical trials and clinical routine as a quickly available disease activity score incorporating CRP as an objective parameter.

Validation of the ASDAS with a quick quantitative CRP assay (ASDAS-Q) in patients with axial SpA: a prospective multicentre cross-sectional study.

Objectives: The objective of the study was to validate the Ankylosing Spondylitis Disease Activity Score (ASDAS) based on a quick quantitative C-reactive protein (qCRP) assay (ASDAS-Q) in a multicentre, prospective, cross-sectional study in patients with axial spondyloarthritis (axial SpA). Methods: Disease activity assessment was performed in prospectively recruited patients with axial SpA. Routine laboratory CRP was determined in the central laboratory of each study centre, while quick qCRP and erythrocyte sedimentation rate (ESR) were measured locally. Consequently, ASDAS-CRP, ASDAS-Q using the qCRP and ASDAS-ESR were calculated. The absolute agreement on the disease activity category ascertainment was analysed with cross-tabulations and weighted Cohen's kappa. Bland-Altman plots and intraclass correlation coefficients (ICCs) were used to analyse the criterion validity. Results: Overall, 251 axial SpA patients were included in the analysis. The mean qCRP value (6.34 ± 11.13 mg/l) was higher than that of routine laboratory CRP (5.26 ± 9.35 mg/l). The ICC for routine laboratory CRP versus qCRP was 0.985 [95% confidence interval (CI): 0.972-0.991]. Comparing ASDAS-Q with ASDAS-CRP, 242 of 251 (96.4%) patients were assigned to the same disease activity categories with a weighted Cohen's kappa of 0.966 (95% CI: 0.943-0.988) and ICC of 0.997 (95% CI: 0.994-0.999). Conclusions: ASDAS-Q showed an almost perfect agreement with ASDAS-CRP in the assignment to specific disease activity categories. Consequently, ASDAS-Q using the qCRP value can be applied as an accurate and quickly available alternative to ASDAS-CRP, thus facilitating the implementation of the treat-to-target concept in clinical trials and clinical routine.

Glucocorticoids Are Not Associated with Bone Mineral Density in Patients with Polymyalgia Rheumatica, Giant Cell Arteritis and Other Vasculitides-Cross-Sectional Baseline Analysis of the Prospective Rh-GIOP Cohort.

BACKGROUND: Glucocorticoids (GCs) can cause osteoporosis (OP). Prior observational research on bone density and the effects of GCs in polymyalgia rheumatica (PMR) and vasculitides is scarce and inconclusive. METHODS: Rh-GIOP is a prospective cohort study of bone health in patients with inflammatory rheumatic diseases. In this cross-sectional baseline analysis, we focused on patients with PMR and different forms of vasculitides. Multivariable linear regression was used to model the effect of current and cumulative GC intake on the minimum T-score at any site (mTs; at either lumbar spine or hip), with comprehensive adjustment for confounders. In separate models, GCs were modelled both as continuous and categorical predictors. Sensitivity analyses, stratifying by measurement site and disease, were conducted. RESULTS: A total of 198 patients, with a mean age of 67.7 ± 11.4 years and a mean disease duration of 5.3 ± 6.3 years, were included. Most patients suffered from PMR (36%), giant cell arteritis (26%) or granulomatosis with polyangiitis (17%). Women comprised 66.7% of the patients, and 87.4% were currently taking GCs. The mean CRP was 13.2 ± 26.1 mg/L. OP diagnosed by dual energy X-ray absorptiometry (DXA) (T-score ≤ -2.5) was present in 19.7% of the patients. While 88% were taking vitamin D supplements, calcium supplementation (4%) and treatment with anti-resorptive agents (17%) were relatively infrequent. Only 7% had a vitamin D deficit. Neither current (ß(continuous model) = -0.01, 97.5% CI -0.02 to 0.01; p(all models) ≥ 0.49) nor cumulative (ß(continuous model) = 0.01, 97.5% CI -0.04 to 0.07; p(all models) ≥ 0.35) GC doses were associated with mTs in any model. CRP was not associated with mTs in any model (p(all models) ≥ 0.56), and no interaction between CRP and GC intake was observed (p for interaction(all models) ≥ 0.32). Across all analyses, lower body mass index (p(all models) ≤ 0.01), history of vertebral fractures (p(all models) ≤ 0.02) and proton-pump inhibitor intake (p(all models) ≤ 0.04) were associated with bone loss. Sensitivity analyses with femoral neck and lumbar spine T-scores as dependent variables led to similar results as the analysis that excluded patients with PMR. CONCLUSIONS: In this cohort of PMR and vasculitides, we found a similar prevalence of OP by DXA to the overall elderly German population. Vitamin D supplementation was very common, and vitamin D insufficiency was less frequent than expected in Germans. There was no association between current or cumulative GC intake, CRP and impaired bone density. Proton-pump inhibitors seem to be a major, but somewhat neglected, risk factor for OP and should be given more attention. Our findings require confirmation from longitudinal analyses of the Rh-GIOP and other cohorts.

Efficacy of tofacitinib in reduction of inflammation detected on MRI in patients with Psoriatic ArthritiS presenTing with axial involvement (PASTOR): protocol of a randomised, double-blind, placebo-controlled, multicentre trial.

INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory disease characterised by synovitis, enthesitis, dactylitis and axial involvement. The prevalence of axial involvement ranges from 25% to 70% in this patient group. Treatment recommendations for axial PsA were mainly extrapolated from guidelines for axial spondyloarthritis, and the main treatment options are non-steroidal anti-inflammatory drugs and biological disease-modifying antirheumatic drugs (tumour necrosis factor, IL-17 and IL-23 inhibitors). Tofacitinib was approved for the treatment of PsA and its efficacy on axial inflammation has been demonstrated in a phase II study of ankylosing spondylitis (AS). This prospective study aims to evaluate the efficacy of tofacitinib in reducing inflammation in the sacroiliac joints (SIJs) and spine on MRI in patients with axial disease of their PsA presenting with active axial involvement compatible with axial PsA. METHODS AND ANALYSES: This is a randomised, double-blind, placebo-controlled, multicentre clinical trial in patients with axial PsA who have evidence of axial involvement, active disease as defined by a Bath AS Disease Activity Index score of ≥4 and active inflammation on MRI of the SIJs and/or spine as assessed by and independent central reader. The study includes a 6-week screening period, a 24-week treatment period, which consist of a 12-week placebo-controlled double-blind treatment period followed by a 12-week active treatment period with tofacitinib for all participants, and a safety follow-up period of 4 weeks. At baseline, 80 subjects shall be randomised (1:1) to receive either tofacitinib or matching placebo for a 12-week double-blind treatment period. At week 12, an MRI of the whole spine and SIJs will be performed to evaluate the primary study endpoint. ETHICS AND DISSEMINATION: The study will be performed according to the ethical principles of the Declaration of Helsinki and the German drug law. The independent ethics committees of each centre approved the ethical, scientific and medical appropriateness of the study before it was conducted. TRIAL REGISTRATION NUMBER: NCT04062695; ClinicalTrials.gov and EudraCT No: 2018-004254-22; European Union Clinical Trials Register.

Diagnosing axial spondyloarthritis: estimation of the disease probability in patients with a priori different likelihoods of the diagnosis.

OBJECTIVE: To evaluate the diagnostic value of SpA parameters and their combination for the diagnosis of axial SpA in patients with an a priori different probability of the diagnosis. METHODS: A total of 361 patients with chronic back pain and suspicion of axial SpA (181 referred by primary care physicians or orthopaedists, 180 recruited via an online screening tool) received a structured rheumatologic examination, which resulted into a diagnosis or exclusion of axial SpA. The prevalence of axial SpA indicating the pre-test probability was 40% in the physician-referred subgroup and 20% in the online screening subgroup. Sensitivities, specificities and likelihood ratios for SpA features were determined in both subgroups and the respective post-test probabilities of axial SpA were calculated. RESULTS: The relative diagnostic value of single SpA features varied substantially between the groups with different referral pathways. For instance, HLA-B27 positivity increased the probability of the presence of axial SpA by 35% to 55% in online-screened patients and by 22% to 62% in physician-referred patients. The absence of HLA-B27 resulted in a sharp decrease in the probability of the presence of axial SpA in physician-referred patients (from 40% to 6%). This decrease was less sharp in the online screening group (from 20% to 10%). These differences were especially relevant in patients with a small number (one to two) of positive SpA features. CONCLUSION: The diagnostic value of SpA features varies in different patient populations, which should be considered in the diagnostic approach.

Comparison of an online self-referral tool with a physician-based referral strategy for early recognition of patients with a high probability of axial spa.

OBJECTIVES: The diagnostic delay in axial spondyloarthritis (axial SpA) remains unacceptably high, with one of the reasons being a late referral. Structured physician-based referral programs are able to improve early diagnosis, but lack of implementation is still an issue. The objective of this study was to evaluate an online self-referral (OSR) tool for patients with back pain and to compare it to an established physician-based referral tool. METHODS: Patients with back pain were included if they either fulfilled the requirements of the OSR tool or were referred by a physician using the Berlin referral tool. Rheumatologists in the specialized center performed a structured assessment in all patients that resulted in the final diagnosis of axial SpA / no axial SpA. Furthermore, we attempted to optimize the OSR tool in terms of maximizing the specificity constrained by a sensitivity of at least 90% of the original strategy. RESULTS: 361 consecutive patients (180 via the OSR and 181 via the Berlin referral tool) were included in the study. A total of 35 patients (19.4%) in the self-referral group and 71 patients (39.2%) in the physician-referral group were finally diagnosed with axial SpA. Axial SpA patients from the OSR group were more often HLA-B27 negative, females, and were more frequently at a non-radiographic stage as compared to axial SpA patients who came via the physician-based tool. Both groups had, however, a similar disease burden. According to the pre-defined selection criterion we identified an optimized combination of ≥2 IBP parameters and ≥1 other SpA parameters (in addition to both stem parameters). CONCLUSIONS: Despite the better performance of the physician-based referral strategy, the proportion of axial SpA among self-referred patients (19.4%) was clearly higher than the assumed 5% prevalence of axial SpA in patients with chronic back pain. Based on our data driven approach the performance of the OSR strategy could be further improved if at least two IBP parameters plus one additional SpA parameter had to be present in addition to the stem parameters. The OSR tool can be used in specialized centers in addition to a physician-based referral strategy to improve early diagnosis and to increase awareness of axial SpA.

Performance of the Ankylosing Spondylitis Disease Activity Score based on a quick quantitative C-reactive protein assay in patients with axial spondyloarthritis.

OBJECTIVES: To evaluate the performance of the Ankylosing Spondylitis Disease Activity Score based on a validated quick quantitative C-reactive protein assay (ASDAS-qCRP) as compared to ASDAS based on a routine lab CRP assay (ASDAS-CRP) and ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR). METHODS: Disease activity assessment was performed in 50 patients with axial spondyloarthritis (axSpA). Routine lab CRP was measured in the central lab while the quantitative quick-CRP assay and ESR measurements were performed locally. ASDAS-CRP, ASDAS-qCRP and ASDAS-ESR were subsequently calculated. RESULTS: The mean (±SD) serum level of the routine lab CRP (6.2±8.3mg/l) was lower than of the quick-CRP (7.4±8.4mg/l) (P<0.05). Whereat, there was no significant difference in the mean values of ASDAS-CRP and ASDAS-qCRP in axSpA patients (2.70±0.94 and 2.74±0.96, respectively, P=0.069), while the ASDAS-ESR (2.85±1.0) was significantly higher than ASDAS-CRP (P=0.036) and numerically higher than ASDAS-qCRP (P=0.125). In 47 of the 50 cases of axSpA (94%), patients were assigned to the same disease activity category according to ASDAS-CRP and ASDAS-qCRP. CONCLUSIONS: ASDAS-qCRP performed similarly well compared to ASDAS-CRP with the absolute agreement on the disease activity category according to the ASDAS of 94%. ASDAS-qCRP is, therefore, feasible for an immediate decision-making in clinical practice and trials aimed at treating to target.

Study protocol: COmparison of the effect of treatment with Nonsteroidal anti-inflammatory drugs added to anti-tumour necrosis factor a therapy versus anti-tumour necrosis factor a therapy alone on progression of StrUctural damage in the spine over two years in patients with ankyLosing spondylitis (CONSUL) - an open-label randomized controlled multicenter trial.

INTRODUCTION: There is some evidence that non-steroidal anti-inflammatory drugs (NSAIDs), in particular celecoxib, might possess not only a symptomatic efficacy but also disease-modifying properties in ankylosing spondylitis (AS), retarding the progression of structural damage in the spine if taken continuously. In contrast, this remains controversial for tumour necrosis factor alpha (TNF-α) inhibitors, despite their good clinical efficacy. The impact of a combined therapy (a TNF inhibitor plus an NSAID) on radiographic spinal progression in AS is unclear. METHODS AND ANALYSIS: The aim of this study is to evaluate the impact of treatment with an NSAID (celecoxib) when added to a TNF inhibitor (golimumab) compared with TNF inhibitor (golimumab) alone on progression of structural damage in the spine over 2 years in patients with AS. The study consists of a 6-week screening period, a 12-week period (phase I: run-in phase) of treatment with golimumab for all subjects followed by a 96-week controlled treatment period (phase II: core phase) with golimumab plus celecoxib versus golimumab alone, and a safety follow-up period of 4 weeks. At week 108, the primary study endpoint radiographic spinal progression (as assessed by the change in the modified Stoke Ankylosing Spondylitis Spine Score after 2 years) will be evaluated. ETHICS AND DISSEMINATION: The study will be performed according to the principles of good clinical practice and the German drug law. The written approval of the independent ethics committee and of the German federal authority have been obtained. On study completion, results are expected to be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov register (NCT02758782) and European Union Clinical Trials Register (EudraCT No 2016-000615-33).

Trabecular reorganization in consecutive iliac crest biopsies when switching from bisphosphonate to strontium ranelate treatment.

BACKGROUND: Several agents are available to treat osteoporosis while addressing patient-specific medical needs. Individuals' residual risk to severe fracture may require changes in treatment strategy. Data at osseous cellular and microstructural levels due to a therapy switch between agents with different modes of action are rare. Our study on a series of five consecutively taken bone biopsies from an osteoporotic individual over a six-year period analyzes changes in cellular characteristics, bone microstructure and mineralization caused by a therapy switch from an antiresorptive (bisphosphonate) to a dual action bone agent (strontium ranelate). METHODOLOGY/PRINCIPAL FINDINGS: Biopsies were progressively taken from the iliac crest of a female patient. Four biopsies were taken during bisphosphonate therapy and one biopsy was taken after one year of strontium ranelate (SR) treatment. Furthermore, serum bone markers and dual x-ray absorptiometry measurements were acquired. Undecalcified histology was used to assess osteoid parameters and bone turnover. Structural indices and degree of mineralization were determined using microcomputed tomography, quantitative backscattered electron imaging, and combined energy dispersive x-ray/µ-x-ray-fluorescence microanalysis. CONCLUSIONS/SIGNIFICANCE: Microstructural data revealed a notable increase in bone volume fraction after one year of SR treatment compared to the bisphosphonate treatment period. Indices of connectivity density, structure model index and trabecular bone pattern factor were predominantly enhanced indicating that the architectural transformation from trabecular rods to plates was responsible for the bone volume increase and less due to changes in trabecular thickness and number. Administration of SR following bisphosphonates led to a maintained mineralization profile with an uptake of strontium on the bone surface level. Reactivated osteoclasts designed tunneling, hook-like intratrabecular resorption sites. The appearance of tunneling resorption lacunae and the formation of both mini-modeling units and osteon-like structures within increased plate-like cancellous bone mass provides additional information on the mechanisms of strontium ranelate following bisphosphonate treatment, which may deserve special attention when monitoring a treatment switch.

Impairment of postural stabilization systems in musicians with playing-related musculoskeletal disorders.

OBJECTIVE: Recent research demonstrates the importance of postural stabilization systems (PSS) in back pain. The purpose of this study was to examine the frequency of PSS disturbances in musicians experiencing playing-related musculoskeletal disorders (PRMDs). METHODS: Analysis for the presence of impaired PSS (lumbopelvic and scapular stabilizing system dysfunction, upper crossed syndrome) in 84 musicians. RESULTS: Analysis of clinical examination data revealed dysfunctions of the PSS to be present in 78 (93%) of these subjects. Eighty-five percent were found to have impairments of scapular, 71% impairments of lumbopelvic stabilization system, and 57% were found to have upper crossed syndrome. Subgroup analysis (upper strings, lower strings, wind and keyboard instruments) showed significantly more impairment of the lumbopelvic stabilization system for upper and lower strings (P = .008), whereas similar rates for disturbances of scapular stabilizers and upper crossed syndrome were seen across subgroups. Furthermore, significant sex differences with a higher frequency of scapular stabilizers (P = .014) and upper crossed syndrome (P < .001) in women were present. CONCLUSION: This study suggests that insufficiencies of the postural stabilization systems play an important role in the manifestation of musculoskeletal pain and PRMD in musicians. Although there are no prospective research data concerning PSS in musicians, the present authors' empirical observations and clinical experience support the notion that the clinical course and therapeutic outcomes of PRMD bear relationship to the function of the stabilization systems. We therefore argue for a greater emphasis on the examination and training of the postural systems in the integrated prevention, treatment, and rehabilitation of musicians.

Professional musicians with craniomandibular dysfunctions treated with oral splints.

Craniomandibular dysfunction (CMD) symptoms occur frequently in violin/viola and wind players and can be associated with pain in the neck, shoulders and arm. In the current study, the effect of oral splint treatment of CMD on reducing pain and symptoms especially in these areas was investigated. Thirty (30) musicians undergoing CMD treatment with oral splints participated in this study. They completed a questionnaire that addressed CMD symptoms, localization of pain, and subjective changes in symptoms. Pain in the shoulder and/or upper extremity was the most frequent symptom reported by 83% of subjects, followed by neck pain (80%) and pain in the teeth/TMJ regions (63%). Treatment with oral splints contributed to a significant decrease in neck pain in 91%, teeth/TMJ pain in 83%, and shoulder and upper extremity pain in 76% of the musicians. Eighty percent (80%) of the patients reported improvement of their predominant symptoms. CMD can be a potential cause for pain in the neck, shoulders, and upper extremities of musicians. It is paramount that musicians with musculoskeletal problems be examined for CMD symptoms. Treatment with oral splints seems to be valuable. Further prospective, randomized controlled studies are necessary to confirm efficacy of oral splint treatment in CMD-associated pain and problems in the neck, shoulder, and the upper extremities in musicians.