[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.

[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.

[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.

[Research consortium Neuroimmunology and pain in the research network musculoskeletal diseases]. / Forschungsverbund Neuroimmunologie und Schmerz (Neuroimpa) im Forschungsnetz Muskuloskelettale Erkrankungen.

BACKGROUND: The research consortium Neuroimmunology and Pain (Neuroimpa) explores the importance of the relationships between the immune system and the nervous system in musculoskeletal diseases for the generation of pain and for the course of fracture healing and arthritis. MATERIAL AND METHODS: The spectrum of methods includes analyses at the single cell level, in vivo models of arthritis and fracture healing, imaging studies on brain function in animals and humans and analysis of data from patients. RESULTS: Proinflammatory cytokines significantly contribute to the generation of joint pain through neuronal cytokine receptors. Immune cells release opioid peptides which activate opioid receptors at peripheral nociceptors and thereby evoke hypoalgesia. The formation of new bone after fractures is significantly supported by the nervous system. The sympathetic nervous system promotes the development of immune-mediated arthritis. The studies show a significant analgesic potential of the neutralization of proinflammatory cytokines and of opioids which selectively inhibit peripheral neurons. Furthermore, they show that the modulation of neuronal mechanisms can beneficially influence the course of musculoskeletal diseases. DISCUSSION: Interventions in the interactions between the immune system and the nervous system hold a great therapeutic potential for the treatment of musculoskeletal diseases and pain.

[Treat-to-target (T2T) recommendation for patients with spondyloarthritis - translation into German]. / "Treat-to-target (T2T)" Empfehlungen für die Behandlung von Patienten mit Spondyloarthritis ­ Übersetzung ins Deutsche.

The management of patients with spondyloarthritis (SpA) has experienced a paradigm shift in recent years. This is true for the treatment of axial as well as peripheral manifestations. International treat to target (T2T) recommendations for SpA based on the T2T strategy have now also been published, which contain 5 higher level principles (A-E) in addition to the 15 recommendations. In order to make the recommendations known and to promote national distribution, German experts have now issued a translation of the T2T recommendations for SpA into German.

[Enthesitis in connection with spondyloarthritides]. / Enthesitis im Rahmen von Spondyloarthritiden.

Enthesitis is a frequent manifestation in spondyloarthritis (SpA) and psoriatic arthritis (PsA) and can be found in up to 40% of patients with SpA. Because of the pathognomonic relevance the classification criteria for SpA and PsA use enthesitis as an entrance or secondary criterion. Enthesitis is most frequently localized at the heel but it can occur at any insertion of an enthesis into the bone. When diagnosing enthesitis differential diagnoses should be considered, mechanical-degenerative causes and fibromyalgia in particular should be excluded. The imaging techniques power Doppler ultrasound (PDUS) and magnetic resonance imaging (MRI) are most helpful in making the diagnosis. The therapeutic options for enthesitis are limited. Nonsteroidal antirheumatic drugs (NSARD) and local injections of corticosteroids are recommended. In small clinical trials no efficacy of disease modifying antirheumatic drugs (DMARD) could be demonstrated. In contrast, tumor necrosis factor alpha (TNF-alpha) blockers were shown to be highly effective in randomized controlled trials for SpA and PsA but they are not currently approved for enthesitis only.

[Enthesitis in the context of spondyloarthritides]. / Enthesitis im Rahmen von Spondyloarthritiden.

Enthesitis is a frequent manifestation in spondyloarthritis (SpA) and psoriatic arthritis (PsA) and can be found in up to 40 % of patients with SpA. Because of the pathognomonic relevance the classification criteria for SpA and PsA use enthesitis as an entrance or secondary criterion. Enthesitis is most frequently localized at the heel but it can occur at any insertion of an enthesis into the bone. When diagnosing enthesitis differential diagnoses should be considered, mechanical-degenerative causes and fibromyalgia in particular should be excluded. The imaging techniques power Doppler ultrasound (PDUS) and magnetic resonance imaging (MRI) are most helpful in making the diagnosis. The therapeutic options for enthesitis are limited. Nonsteroidal antirheumatic drugs (NSARD) and local injections of corticosteroids are recommended. In small clinical trials no efficacy of disease modifying antirheumatic drugs (DMARD) could be demonstrated. In contrast, tumor necrosis factor alpha (TNF-alpha) blockers were shown to be highly effective in randomized controlled trials for SpA and PsA but they are not currently approved for enthesitis only.

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

BACKGROUND: The efficacy of oral prednisolone in patients with active ankylosing spondylitis (AS) has not been studied to date. METHODS: In this double-blind, randomised, placebo-controlled trial, patients with AS with active disease despite taking non-steroidal antirheumatic drugs were randomised to three groups in which they were either treated with 20 mg (n=13) or 50 mg (n=12) of prednisolone, or placebo (n=14), administered orally every day for a total of 2 weeks. The primary endpoint was defined as a 50% improvement of the Bath AS Disease Activity Index (BASDAI) at week 2. RESULTS: The primary endpoint was reached in 33% and 27% of the patients treated with 50 and 20 mg of prednisolone, respectively, versus only 8% on placebo (p=0.16 and p=0.30). However, the mean improvement of BASDAI score was significantly higher in the 50 mg prednisolone compared to the placebo group (2.39±0.5 vs 0.66±0.49, p=0.03), while there was only a small change in the 20 mg group (1.19±0.53; p=0.41). The results for other outcome parameters were similar. CONCLUSIONS: Oral prednisolone 50 mg per day, but not low dose prednisolone, showed a short-term response that was significantly higher than placebo. The clinical significance and the duration of this effect warrant further study.

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.

Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial.

PURPOSE: To evaluate the potential of etanercept versus sulfasalazine to reduce active inflammatory lesions on whole-body MRI in active axial spondyloarthritis with a symptom duration of less than 5 years. METHODS: Patients were randomly assigned to etanercept (n=40) or sulfasalazine (n=36) treatment over 48 weeks. All patients showed active inflammatory lesions (bone marrow oedema) on MRI in either the sacroiliac joints or the spine. MRI was performed at weeks 0, 24 and 48 and was scored for active inflammatory lesions in sacroiliac joints and the spine including posterior segments and peripheral enthesitis by two radiologists, blinded for treatment arm and MRI time point. RESULTS: In the etanercept group, the reduction of the sacroiliac joint score from 7.7 at baseline to 2.0 at week 48 was significantly (p=0.02) larger compared with the sulfasalazine group from 5.4 at baseline to 3.5 at week 48. A similar difference in the reduction of inflammation was found in the spine from 2.2 to 1.0 in the etanercept group versus from 1.4 to 1.3 in the sulfasalazine group between baseline and week 48, respectively (p=0.01). The number of enthesitic sites also improved significantly from 26 to 11 in the etanercept group versus 24 to 26 in the sulfasalazine group (p=0.04 for difference). 50% of patients reached clinical remission in the etanercept group versus 19% in the sulfasalazine group at week 48. CONCLUSION: In patients with early axial spondyloarthritis active inflammatory lesions detected by whole-body MRI improved significantly more in etanercept versus sulfasalazine-treated patients. This effect correlated with a good clinical response in the etanercept group.

Treatment of active ankylosing spondylitis with abatacept: an open-label, 24-week pilot study.

OBJECTIVE: To prospectively explore the short-term efficacy and safety of abatacept in patients with ankylosing spondylitis (AS). METHODS: In this prospective open-label pilot study, abatacept (10 mg/kg) was administered intravenously on days 1, 15, 29 and every 28 days thereafter up to week 24 in 15 tumour necrosis factor α (TNFα)-inhibitor naive patients (group 1) and 15 patients with inadequate response to TNFα inhibitors (group 2) with active AS. The primary end point was the proportion of patients with 40% improvement according to the Assessment of SpondyloArthritis international Society criteria (ASAS40) in both groups at week 24. RESULTS: At week 24, ASAS40 was reached by 13% of group 1 and 0% of group 2; 20% improvement (ASAS20) was reached by 27% and 20%, respectively. There was no significant change of Bath Ankylosing Spondylitis Disease Activity Index score, patient global assessment or C reactive protein. Overall, abatacept was well tolerated. CONCLUSIONS: In this pilot open-label AS study a major response was not observed.

Use of methotrexate in patients with ankylosing spondylitis.

The disease modifying antirheumatic drug (DMARD) methotrexate (MTX) is widely used and well accepted for the treatment of patients with rheumatoid arthritis (RA). In ankylosing spondylitis (AS), the use of MTX is not recommended for the axial manifestations and may have some efficacy in the peripheral involvement. For this disease there is a lack of clinical trials, and most of the trials did not show efficacy on the axial symptoms of the disease. Furthermore, there is no evidence that MTX increases the effects or prevents the side effects of TNF-blockers if given in combination. In this paper the available data of MTX in AS will be discussed.

Disease-modifying anti-rheumatic drugs in rheumatoid arthritis and ankylosing spondylitis.

Disease modifying antirheumatic drugs (DMARDs) are widely used and well accepted for the treatment of patients with rheumatoid arthritis (RA). Many studies have been performed with monotherapy and combinations of DMARDs showing their efficacy and safety. In ankylosing spondylitis (AS) DMARDs, sulfasalazine especially, are recommended only for the peripheral involvement and not for the axial symptoms. For this disease there is a lack of clinical trials and most of the trials did not show efficacy on the axial symptoms of the disease. In this paper, the differences and similarities of DMARDs in the treatment of RA and AS patients will be discussed.

Multicenter open-label study with infliximab in active ankylosing spondylitis over 28 weeks in daily practice.

OBJECTIVE: The aim of this study was to prospectively investigate the therapeutic efficacy and safety of infliximab therapy in NSAID-refractory AS patients, with special emphasis on impact on quality of life in daily practice. PATIENTS AND METHODS: 101 AS patients with active disease (mean Bath ankylosing spondylitis activity index (BASDAI) 6.3, range 4.0-9.8) were enrolled in an open label study. Infliximab 5 mg/kg body weight was administered intravenously at week 0, 2, 6, 12, 18 and 24 followed by a final assessment at week 28. Clinical assessments included quality of life (SF-36, primary endpoint), disease activity (BASDAI), function (BASFI), metrology (BASMI), patients' and physicians' global, pain, work productivity (WPAI) and CRP. RESULTS: Using an intention to treat (ITT) analysis, the mean SF-36 physical health component improved from 27.6 at baseline to 40.9 at study end (p<0.001), the mean SF-36 mental health component improved from 44.4 at study entry to 53.0 at final assessment (p<0.001). The Assessment of AS (ASAS-) 20 short-term improvement criteria were reached by 80.2% of patients, ASAS 40 by 60.4% and the ASAS criteria for partial remission were reached by 27.7% of patients. A BASDAI 50% improvement was found in 66.3% of patients. Comparable significant improvements were found for mean BASDAI; BASFI, BASMI, patients' and physicians' global, general pain, CRP and WPAI. 11.8% of patients stopped therapy because of side effects. CONCLUSIONS: Infliximab showed high efficacy and safety when used by non-specialised rheumatologists in daily practice.

Radiographic progression in patients with ankylosing spondylitis after 4 yrs of treatment with the anti-TNF-alpha antibody infliximab.

OBJECTIVES: Anti-tumour necrosis factor therapy with infliximab has been shown to improve signs and symptoms of patients with active ankylosing spondylitis (AS). The objective of this article was to study the effect of infliximab on structural changes in AS over 4 yrs. METHODS: Conventional radiographs of the cervical and the lumbar spine of 33 AS patients at baseline (BL), after 2 (FU1) and after 4 yrs (FU2) of infliximab therapy were scored by the modified Stokes ankylosing spondylitis spinal score (mSASSS). Definite baseline damage was defined when at least one syndesmophyte (mSASSS >/=2) was seen. Definite radiographic progression was defined as a change from 0 or 1 to syndesmophytes or ankylosis (mSASSS >/=2). RESULTS: The mean change over 4 yrs was 1.6 +/- 2.6 mSASSS units (P = 0.001), (0.9 +/- 2.3 for BL-FU1 vs 0.7 +/- 1.6 for FU1-FU2). This is less radiographic progression in comparison with published data from the OASIS cohort (4.4 within 4 yrs). Definite radiographic progression was found in 10/33 (30.3%) patients for BL-FU2. Patients with definite damage at BL developed more chronic changes at FU2 (2.3 +/- 3.1, P = 0.003) than those with no damage at BL (0.7 +/- 1.5, P = 0.08). Four out of seven patients with no damage at BL showed radiographic deterioration after 4 yrs. The change of the mean mSASSS in comparison with BL was significantly different after 2 (P = 0.007) but not after 4 yrs of infliximab therapy. CONCLUSIONS: There is some radiographic progression after 2 and 4 yrs of infliximab therapy in AS patients. A comparison with the historical OASIS cohort suggests that infliximab may decelerate progression of structural changes. Larger studies are needed to confirm this finding.

Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor alpha agents.

OBJECTIVE: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are clinically and pathologically linked. Anti-tumor necrosis factor (anti-TNF) agents are efficacious in treating AS, but not all are equally effective in treating IBD (Crohn's disease [CD] and ulcerative colitis [UC]). The purpose our study was to analyze the incidence of flares and new onset of IBD in patients with AS treated with anti-TNF agents. METHODS: Data from 9 trials, 7 placebo-controlled trials and 2 open studies, were analyzed. RESULTS: Data were available on 419 AS patients exposed to etanercept (625 patient-years), 366 exposed to infliximab (618 patient-years), 295 exposed to adalimumab (132 patient-years), and 434 placebo patients (150 patient-years). A history of IBD was reported in 76 of 1,130 patients (6.7%). There were 2 reports of IBD while receiving placebo (1.3 per 100 patient-years), 1 while receiving infliximab, and 3 while receiving adalimumab. Among the 14 IBD cases receiving etanercept (2.2 per 100 patient-years) there were 8 CD and 6 UC cases, significantly different from infliximab (P = 0.01) but not from placebo. Patients with a history of IBD had an IBD flare odds ratio of 18.0 (95% confidence interval [95% CI] 2-154) while taking etanercept and 4.2 (95% CI 0.4-44) while taking adalimumab, in comparison with infliximab. The incidence rates of new onset of IBD showed no significant difference between etanercept (0.8 per 100 patient-years) and placebo (0.5 per 100 patient-years). CONCLUSION: New onset and flare of IBD are infrequent events in AS patients receiving anti-TNF therapy. Infliximab (but not etanercept) largely prevents IBD activity. More data are required for adalimumab. The incidence of new onset of IBD was statistically not different from placebo for all anti-TNF agents.

Progression of radiographic damage in patients with ankylosing spondylitis: defining the central role of syndesmophytes.

BACKGROUND: Structural changes such as erosions, syndesmophytes and ankylosis are characteristic of ankylosing spondylitis (AS). These can be quantified by the modified Stokes Anklylosing Spondylitis Spinal Score (mSASSS). It is unknown which radiographic feature is most relevant for the assessment of change and the prediction of future damage in AS. OBJECTIVES: To analyse radiographic progression in AS by using different assessments to define the most important changes. METHODS: Spinal radiographs of 116 patients with AS were scored by the mSASSS at baseline (BL) and after 2 years. Radiographic progression was assessed by differentiating (1) any change; (2) progression to syndesmophytes/ankylosis (definite change); and (3) changes exceeding the smallest detectable change (SDC) as predefined. A growth angle of 45 degrees was used to differentiate syndesmophytes from spondylophytes. RESULTS: Some radiographic progression after 2 years was detected in 42% of patients, novel syndesmophytes in 31% of patients, and, using the SDC (calculated at 2 mSASSS units) as cut-off, progression was seen in 28% of patients. Thus, in 74% of the patients changes were because of syndesmophytes and/or ankylosis. Using the predefined cut-off, only 12% of all syndesmophytes were spondylophytes. Patients with such changes were of older age. Definite radiographic progression was found in 44% of the patients with syndesmophytes/ankylosis at BL (n = 57) versus 19% (p = 0.03) of the patients without such changes (n = 59). CONCLUSIONS: Syndesmophytes and ankylosis are the most relevant structural changes in AS, and also in the mSASSS. Development of just one syndesmophyte within 2 years indicates progression of structural changes in AS; this is relevant for clinical practice. Syndesmophytes are the best predictors of radiographic progression.

No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial.

OBJECTIVE: To examine the potential therapeutic effect of methotrexate 20 mg given weekly as subcutaneous injections to 20 patients with ankylosing spondylitis refractory to non-steroidal antirheumatic drugs. PATIENTS AND METHODS: 20 patients with ankylosing spondylitis, a mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 5.6 (range 4-9.3) and predominantly axial manifestations were treated with weekly 15 mg methotrexate subcutaneously for 4 weeks, which was then increased to 20 mg subcutaneously for the next 12 weeks. Clinical outcome assessments included, among others, BASDAI score physical function, spinal mobility, patients' and physicians' global assessment (visual analogue scale), peripheral joint assessment, quality of life (Short Form 36) and C reactive protein. The primary end point of the study was a 20% improvement on the ASsessments in Ankylosing Spondylitis (ASAS 20) scale. RESULTS: Using an intention-to-treat analysis, ASAS 20 was achieved in only 25% of patients. An ASAS 40 response was achieved in 10% of patients, and no patient reached an ASAS 70 response or the ASAS criteria for partial remission. For the mean BASDAI score, no change was observed between baseline and week 16 (baseline 5.6 v week 16, 5.6). No improvement was observed in any of the clinical parameters or C reactive protein, except a small but non-significant decrease in the number of swollen joints. CONCLUSIONS: In this open study, methotrexate did not show any benefit for axial manifestations in patients with active ankylosing spondylitis beyond the expected placebo response.