[Development of quality standards for patients with axial spondyloarthritis for use in Germany]. / Entwicklung von Qualitätsstandards für Patient*innen mit axialer Spondyloarthritis zum Einsatz in Deutschland.

Quality standards (QS) are measurable constructs designed to quantify gaps in care and subsequently to improve quality of care. The Assessment of SpondyloArthritis International Society (ASAS) recently generated and published international QS for the management of patients with axial spondyloarthritis (axSpA) for the first time. The German Society of Rheumatology (DGRh) then decided to translate, review and possibly adopt these standards by a group of experts from different care settings. Against this background, national QS for the management of patients with axSpA for Germany were developed for the first time. The main focus was on feasibility and practical relevance. Ultimately, nine QS were defined with which the quality of care in Germany can and should be measured and improved.

The ASAS-OMERACT core domain set for axial spondyloarthritis.

BACKGROUND: The current core outcome set for ankylosing spondylitis (AS) has had only minor adaptations since its development 20 years ago. Considering the significant advances in this field during the preceding decades, an update of this core set is necessary. OBJECTIVE: To update the ASAS-OMERACT core outcome set for AS into the ASAS-OMERACT core outcome set for axial spondyloarthritis (axSpA). METHODS: Following OMERACT and COMET guidelines, an international working group representing key stakeholders (patients, rheumatologists, health professionals, pharmaceutical industry and drug regulatory agency representatives) defined the core domain set for axSpA. The development process consisted of: i) Identifying candidate domains using a systematic literature review and qualitative studies; ii) Selection of the most relevant domains for different stakeholders through a 3-round Delphi survey involving axSpA patients and axSpA experts; iii) Consensus and voting by ASAS; iv) Endorsement by OMERACT. Two scenarios are considered based on the type of therapy investigated in the trial: symptom modifying therapies and disease modifying therapies. RESULTS: The updated core outcome set for axSpA includes 7 mandatory domains for all trials (disease activity, pain, morning stiffness, fatigue, physical function, overall functioning and health, and adverse events including death). There are 3 additional domains (extra-musculoskeletal manifestations, peripheral manifestations and structural damage) that are mandatory for disease modifying therapies and important but optional for symptom modifying therapies. Finally, 3 other domains (spinal mobility, sleep, and work and employment) are defined as important but optional domains for all trials. CONCLUSION: The ASAS-OMERACT core domain set for AS has been updated into the ASAS-OMERACT core domain set for axSpA. The next step is the selection of instruments for each domain.

Unveiling axial involvement in psoriatic arthritis: An ancillary analysis of the ASAS-perSpA study.

OBJECTIVE: To determine the clinical profile of axial psoriatic arthritis (PsA) in a worldwide setting. Secondly, to identify factors associated with the development of axial involvement in patients with PsA. METHODS: Data from 3684 patients with axial spondyloarthritis (axSpA) or PsA from the ASAS-perSpA study were analysed. The ASAS-perSpA is a cross-sectional study that recruited consecutive patients with SpA (as diagnosed by their rheumatologist) from 68 centers worldwide and collected patient and disease data. First, 2651 axSpA patients and 367 PsA patients with any history of axial involvement (axPsA) were compared using logistic regression to later identify predictive factors for rheumatologist diagnosis of axPsA. Secondly, 367 axPsA patients were compared with 666 PsA patients lacking axial involvement (peripheral PsA [pPsA]) and the characteristics associated with axial manifestations were explored by logistic regression analysis. RESULTS: Patients with axPsA were older and less frequently males or HLA*B27 positive in comparison with axSpA patients. Additionally, while patients with axPsA had more peripheral manifestations and psoriasis, other extra-musculoskeletal manifestations (IBD and uveitis) were more frequent in those with axSpA. In the multivariable analysis, older age at diagnosis (OR = 1.04), peripheral arthritis (OR = 7.32) and dactylitis (OR = 2.82) were significantly associated with the diagnosis of axPsA. However, uveitis (OR = 0.22), IBD (OR = 0.12), HLA*B27 carriership (OR = 0.26) or sacroiliitis on imaging (OR = 0.5) were inversely associated with axPsA diagnosis as compared to axSpA. Axial involvement in patients with PsA was significantly associated with male gender (OR = 1.68), elevated CRP (OR = 2.87) and the absence of psoriasis (OR = 0.33). CONCLUSION: In this worldwide setting axPsA was defined by rheumatologists as a unique phenotype, with disease features lying between axSpA and pure pPsA.

The risk of malignancy in patients with secukinumab-treated psoriasis, psoriatic arthritis and ankylosing spondylitis: analysis of clinical trial and postmarketing surveillance data with up to five years of follow-up.

BACKGROUND: Data on the use of biologic therapy and malignancy risk are inconsistent due to limited long-term robust studies. OBJECTIVES: To assess the malignancy risk in patients with secukinumab-treated psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS). METHODS: This integrated safety analysis from both the secukinumab clinical trial programme and postmarketing safety surveillance data included any patient receiving at least one approved dose of secukinumab with a maximum of 5 years of follow-up. Safety analyses evaluated the rate of malignancy using exposure-adjusted incidence rates [EAIR; incidence rates per 100 patient treatment-years (PTY)]. Standardized incidence ratios (SIRs) were reported using the Surveillance, Epidemiology, and End Results Program (SEER) database as a reference population. Crude incidence of malignancy was also reported using postmarketing surveillance data. RESULTS: Safety data from 49 clinical trials with secukinumab-treated patients were included: 10 685 patients with psoriasis, 2523 with PsA and 1311 with AS. Across indications over a 5-year period, the EAIR of malignancy was 0·85 per 100 PTY [95% confidence interval (CI) 0·74-0·98] in secukinumab-treated patients, corresponding to 204 patients per 23 908 PTY. Overall, the observed vs. expected number of malignancies from secukinumab clinical trial data were comparable, as indicated by an SIR of 0·99 (95% CI 0·82-1·19) across indications. The estimated crude cumulative incidence reporting rate per 100 PTY for malignancy was 0·27 in the postmarketing surveillance data across indications with a cumulative exposure of 285 811 PTY. CONCLUSIONS: In this large safety analysis, the risk of malignancy was low for up to 5 years of secukinumab treatment. These data support the long-term use of secukinumab in these indications.

[Pathogenesis of spondylarthritis : Relevance for treatment]. / Pathogenese der Spondyloarthritiden : Relevanz für die Therapie.

Although the pathogenesis of spondylarthritis (SpA) has been the subject of intensive research in recent years, the consequences for treatment are relatively minor. Basic research studies indicated a potentially important role of the cytokines tumor necrosis factor (TNF) alpha and interleukin (IL)-17 for the pathogenesis of SpA but their outstanding role could then only be demonstrated by their inhibition in clinical studies, while other promising targets, such as IL­23 and IL­6 could not be shown to be relevant (at least against axial manifestations) in clinical studies. The intestinal microbiota probably plays an important role in the pathogenesis but not yet for the treatment of SpA. Ultimately, early effective and long-term suppression of inflammation is currently the best method to prevent ankylosis in the long run.

[Cost of illness in axial spondylarthritis for patients with and without tumor necrosis factor inhibitor treatment: results of a routine data analysis]. / Krankheitskosten bei axialer Spondyloarthritis für Patienten mit und ohne Tumor-Nekrose-Faktor-Inhibitor-Behandlung: Ergebnisse einer Routinedatenanalyse.

BACKGROUND: Tumour necrosis factor-alpha inhibitors (TNFi) are an effective but expensive treatment option in axial spondylarthritis (axSpA) patients who fail to achieve disease control under conventional treatment. OBJECTIVE: The aim of this study was to assess the cost of illness in axSpA patients treated with and without TNFi. METHODS: Using German health insurance data, patients with axSpA who newly received TNFi between 2011 and 2015 were identified and matched by age and sex to a reference group of patients with axSpA without TNFi treatment. Costs for services performed in an outpatient setting, inpatient care, pharmacotherapy and for productivity loss due to absence from paid work were analyzed over a 2-year period. In patients treated with TNFi , the 2­year period included 1 year before and 1 year after the initiation of TNFi. RESULTS: Data from 1455 axSpA patients who received TNFi treatment were included in the analyses. Costs for services performed in an outpatient setting, inpatient care, pharmacotherapy (excluding TNFi) as well as productivity loss significantly decreased after initiation of TNFi. Mean total costs increased from €â€¯6075 in the year prior to TNFi initiation to €â€¯27,871 in the year after TNFi initiation. Excluding costs for TNFi, total costs decreased by 22% to €â€¯4761. Mean total costs among the reference group of 1455 age and sex-matched axSpA patients who did not receive TNFi remained stable over 2 years: €â€¯3939 in the first year vs. €â€¯3832 in the second year. CONCLUSION: Initiation of TNFi treatment led to a sharp increase in the total costs of axSpA patients. Part of this increase was offset by a decrease of costs for services performed in an outpatient setting, inpatient care, pharmacotherapy (excluding TNFi) as well as productivity loss. In patients who did not receive TNFi, the costs remained stable over 2 years.

[Reality of care for musculoskeletal diseases at the population level : Results of the PROCLAIR collaborative project. German version]. / Versorgungswirklichkeit muskuloskeletaler Erkrankungen auf Bevölkerungsebene : Erkenntnisse aus dem Verbundprojekt PROCLAIR.

BACKGROUND: The objective of the research consortium PROCLAIR was to gain population level knowledge on the treatment of patients with rheumatoid arthritis (RA), axial spondylarthritis (axSpA) and osteoarthritis (OA) in Germany. AIMS: A main question of the consortium was whether it is possible to identify groups of people who were exposed to a particular risk of undersupply or oversupply of treatment. In addition, the study investigated the validity of claims data for these diseases as a basis for further studies. PATIENTS AND METHODS: Cross-sectional surveys were carried out among insurees of the BARMER statutory health insurance fund whose claims data included RA, axSpA and OA diagnoses. The questionnaire data were linked with the claims data of the insured persons if they agreed. RESULTS: In all three diseases risk groups for care deficits could be identified. Persons with RA who are not treated by a specialist have less access to drug treatment. Physical therapy is prescribed for all three diagnoses at a low level, even for people undergoing joint replacement surgery. A connection between depressive symptoms and disease activity or function in axSpA was shown. In addition to the results relevant to care, the PROCLAIR network has also made contributions to critically assess the quality of health insurance data. DISCUSSION: The combination of billing data with survey data enables a comprehensive description of the treatment of musculoskeletal diseases. Particularly relevant factors are the specialization of the physician, sociodemographic parameters of the patients and the region of residence. In particular, access to treatment cannot be investigated in randomized clinical trials.

Reality of care for musculoskeletal diseases at the population level : Results of the PROCLAIR collaborative project.

BACKGROUND: The objective of the research consortium PROCLAIR was to gain population level knowledge on the treatment of patients with rheumatoid arthritis (RA), axial spondylarthritis (axSpA) and osteoarthritis (OA) in Germany. AIMS: A main question of the consortium was whether it is possible to identify groups of people who were exposed to a particular risk of undersupply or oversupply of treatment. In addition, the study investigated the validity of claims data for these diseases as a basis for further studies. PATIENTS AND METHODS: Cross-sectional surveys were carried out among insurees of the BARMER statutory health insurance fund whose claims data included RA, axSpA and OA diagnoses. The questionnaire data were linked with the claims data of the insured persons if they agreed. RESULTS: In all three diseases risk groups for care deficits could be identified. Persons with RA who are not treated by a specialist have less access to drug treatment. Physical therapy is prescribed for all three diagnoses at a low level, even for people undergoing joint replacement surgery. A connection between depressive symptoms and disease activity or function in axSpA was shown. In addition to the results relevant to care, the PROCLAIR network has also made contributions to critically assess the quality of health insurance data. DISCUSSION: The combination of billing data with survey data enables a comprehensive description of the treatment of musculoskeletal diseases. Particularly relevant factors are the specialization of the physician, sociodemographic parameters of the patients and the region of residence. In particular, access to treatment cannot be investigated in randomized clinical trials.

[Health care and disease burden in persons with axial spondyloarthritis in Germany]. / Gesundheitsversorgung und Krankheitslast bei Personen mit axialer Spondyloarthritis in Deutschland.

BACKGROUND: Only very few data are available on the comprehensive care in patients with axial spondylarthritis (axSpA), one of the most frequent inflammatory rheumatic disease. OBJECTIVE: Description of the comprehensive care and common prescription patterns of medications and other therapies in patients with axSpA depending on the type of medical care by rheumatologists or nonrheumatologists. METHODS: A cross-sectional analysis was performed based on claims data of the BARMER health insurance company (in 2015) and a questionnaire, which was sent to a representative sample of patients with axSpA (International Classification of Diseases, 10th revision, German modification, ICD-10-GM, code M45) aged 18-79 years. A stratified sample of 5000 patients was used. The patients received a postal questionnaire including questions regarding the disease, health-related and psychological parameters and socioeconomic factors. Claims data consisted of demographic factors, medicinal and nonmedicinal treatment and the extra-articular manifestations inflammatory bowel disease, psoriasis and uveitis. RESULTS: A total of 1741 patients (mean age 55.9 years, female 46.4%, 86.2% Human Leucocyte Antigen[HLA]-B27 positive) confirmed the diagnosis and answered the questionnaire. The mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 4.5 and the mean Bath Ankylosing Spondylitis Functional Index (BASFI) 4.1. Of the patients 46% were treated by rheumatologists. There was a substantial difference between patients in rheumatological care and those who were not in rheumatological care regarding prescriptions for drug treatment of axSpA (91.8% versus 66.4%). This difference was especially prominent for prescriptions of biologic disease-modifying antirheumatic drugs: 34.1% of patients in rheumatological care versus 3.1% of patients treated by nonrheumatologists (p < 0.0001), despite similar disease activity in both groups. CONCLUSION: The data show that the majority of patients diagnosed with axSpA did not receive regular care from rheumatologists. This seemed to be associated with insufficient medicinal care at least in some of these patients.

Spinal radiographic progression over 2 years in ankylosing spondylitis patients treated with secukinumab: a historical cohort comparison.

OBJECTIVE: The aim of this study was to compare radiographic progression in patients with ankylosing spondylitis (AS) treated for up to 2 years with secukinumab (MEASURE 1) with a historical cohort of biologic-naïve patients treated with NSAIDs (ENRADAS). METHODS: Baseline and 2-year lateral cervical and lumbar spine radiographs were independently evaluated using mSASSS by two readers, who were blinded to the chronology and cohort of the radiographs. The primary endpoint was the proportion of patients with no radiographic progression (mSASSS change ≤ 0 from baseline to year 2). The Primary Analysis Set included patients with baseline (≤ day 30) and post-baseline day 31-743 radiographs. Sensitivity analyses were performed to assess the robustness of the comparison between the two cohorts, as follows: Sensitivity Analysis Set 1 included all patients with baseline (≤ day 30) and year 2 (days 640-819) radiographs; Sensitivity Analysis Set 2 included all patients with baseline and post-baseline (> day 30) radiographs. RESULTS: A total of 168 patients (84%) from the MEASURE 1 cohort and 69 (57%) from the ENRADAS cohort qualified for the Primary Analysis Set. Over 2 years, the LS (SE) mean change from baseline in mSASSS for the primary analysis was 0.55 (0.139) for MEASURE 1 vs 0.89 (0.216) for ENRADAS (p = 0.1852). Mean changes from baseline in mSASSS were lower in MEASURE 1 vs ENRADAS for the primary and sensitivity analyses. The proportion of patients with no radiographic progression was consistently higher in the MEASURE 1 vs ENRADAS cohort across all cutoffs for no radiographic progression (change in mSASSS from baseline to year 2 of ≤ 0, ≤ 0.5, ≤ 1, and ≤ 2), but the differences were not statistically significant. CONCLUSION: Secukinumab-treated patients demonstrated a numerical, but statistically non-significant, higher proportion of non-progressors and lower change in mSASSS over 2 years versus a cohort of biologic-naïve patients treated with NSAIDs.

[Biomarkers and imaging for diagnosis and stratification of rheumatoid arthritis and spondylarthritis in the BMBF consortium ArthroMark]. / Biomarker und Bildgebung zur Diagnose und Stratifizierung der rheumatoiden Arthritis und Spondylarthritis im BMBF-Verbund ArthroMark.

Rheumatic diseases are among the most common chronic inflammatory disorders. Besides severe pain and progressive destruction of the joints, rheumatoid arthritis (RA), spondyloarthritides (SpA) and psoriatic arthritis (PsA) impair working ability, reduce quality of life and if treated insufficiently may enhance mortality. With the introduction of biologics to treat these diseases, the demand for biomarkers of early diagnosis and therapeutic stratification has been growing continuously. The main goal of the consortium ArthroMark is to identify new biomarkers and to apply modern imaging technologies for diagnosis, follow-up assessment and stratification of patients with RA, SpA and PsA. With the development of new biomarkers for these diseases, the ArthroMark project contributes to research in chronic diseases of the musculoskeletal system. The cooperation between different national centers will utilize site-specific resources, such as biobanks and clinical studies for sharing and gainful networking of individual core areas in biomarker analysis. Joint data management and harmonization of data assessment as well as best practice characterization of patients with new imaging technologies will optimize quality of marker validation.

[Diagnosis and therapy of axial spondyloarthritis including ankylosing spondylitis (Bechterew's disease)]. / Diagnose und Therapie der axialen Spondyloarthritis einschließlich des Morbus Bechterew.

The term axial spondyloarthritis covers patients with established structural changes visible on x-ray in sacroiliac joints and/or in the spine (classical ankylosing spondylitis) but also patients with non-radiographic axial spondyloarthritis in whom early inflammatory signs of the disease can only be visualized with magnetic resonance imaging (MRI). The MRI technique plays an important role in the diagnosis of this disease and an early diagnosis is normally based on a combination of clinical, laboratory and imaging parameters. Only non-steroidal anti-inflammatory drugs and TNF-α blockers are effective in the treatment of axial spondyloarthritis. Patients with short disease duration and elevated acute phase reactant levels demonstrate best therapy response and, therefore, should be closely followed-up and consistently treated.

[Early axial spondyloarthritis. Diagnostic approach and screening]. / Frühe Spondyloarthritiden. Diagnostisches Vorgehen und Screening.

The diagnosis of axial spondyloarthritis (SpA) or ankylosing spondylitis (AS) is often delayed by 5-10 years after the first symptoms have appeared. In order to improve the early diagnosis of SpA an evidenced-based algorithm including clinical, laboratory and imaging parameters was developed. Moreover, the recently published ASAS criteria for axial and peripheral SpA should give rheumatologists more confidence in making the diagnosis of SpA and provide further support for the SpA concept. Furthermore, an easy strategy for the recognition of patients with a high probability of AS/SpA on the primary care level has been developed and recently validated.

Relationship between active inflammatory lesions in the spine and sacroiliac joints and new development of chronic lesions on whole-body MRI in early axial spondyloarthritis: results of the ESTHER trial at week 48.

AIM: To investigate the relationship between active inflammatory lesions on whole-body MRI (wb-MRI) and new development of chronic lesions on T1 MRI in patients with early axial spondyloarthritis (SpA) treated either with etanercept (ETA) or sulfasalazine (SSZ). METHODS: Wb-MRIs of 65 patients treated either with ETA (n=35) or SSZ (n=30) over 1 year were scored for active inflammation, fatty lesions, erosions and ankylosis in the 23 vertebral units (VUs) of the spine and in the sacroiliac joints (SI joints). Scoring was performed by two blinded radiologists. RESULTS: If there was no previous inflammation in the bone no new fatty lesions occurred in SI joint quadrants and only a few (0.6%) in spine VUs. There was a significant relationship between disappearance of inflammation and the appearance of fatty lesions: if baseline inflammation resolved fatty lesions occurred in 10.5% of SI joint quadrants and 17.9% of VUs. If inflammation did not resolve over 1 year, fatty lesions occurred less frequently: 2.4% (SI joint quadrants) and 7.2% (VUs). There was a significantly higher increase of the mean fatty lesion score between baseline and week 48 in the ETA (4.0 vs 4.8 for the SI joints and 1.9 vs 2.7 for the spine) compared to the SSZ (3.0 vs 3.2 for the SI joints and 1.1 vs 1.2 for the spine, respectively) group (p=0.001 and p=0.020 for the differences). No significant changes in the erosion or ankylosis score were observed in any of the two groups during this time. CONCLUSIONS: These data indicate that there is a close interaction between inflammation, tumour necrosis factor blockade and the development of fatty lesions in subchondral bone marrow of patients with axial SpA.

Comparison of a high sensitivity and standard C reactive protein measurement in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis.

OBJECTIVE: This study was aimed at comparing high sensitivity C reactive protein (hsCRP) measurement with routine C reactive protein (CRP) evaluation as disease activity parameters in patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nrSpA). METHODS: A total of 269 patients (153 with AS and 116 with nrSpA) were included. Level of hsCRP was measured using particle-enhanced immunoturbidimetric method with the lowest detected level of 0.1 mg/litre. The hsCRP values were compared to results of routine turbidimetric CRP test with the lowest detected level of 6 mg/litre. RESULTS: In the whole group of patients with AS, hsCRP showed a better than routine CRP correlation with clinical parameters. In the whole group of patients with nrSpA, hsCRP correlated with the level of enthesitis-related tenderness only. In the AS subgroup with a negative routine CRP (<6 mg/litre) there was a clear trend for an increased level of pain, stiffness and functional impairment in patients with higher hsCRP concentration. Such a trend was less pronounced in patients with nrSpA. CONCLUSIONS: hsCRP correlates better than routine CRP with clinical disease activity parameters in patients with axial SpA, especially in AS. Therefore, hsCRP could be superior to standard CRP in assessing disease activity in axial SpA.

A systematic comparison of rheumatoid arthritis and ankylosing spondylitis: non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) play different roles in the management of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). In RA there is minimal evidence that NSAIDs are able to alter the course of disease or prevent joint destruction and, therefore, they should mostly be used as a short-term bridging therapy. In contrast to RA, in AS NSAIDs are considered as a cornerstone of the treatment not only because of a high symptomatic efficacy, but also because they might even retard osteoproliferation and radiographic progression. Considering younger age of AS patients and lower prevalence of comorbidities, they are probably at lower risk for cardiovascular and gastrointestinal side effects of short- and long-term NSAID therapy in comparison to RA.