Search PubMed⌕ Search

Biomedical subjects

J Braun

Publications and source records attributed to J Braun.

At least 55 records · Page 3Linked to original sources
PubMed2005

Assessment of acute spinal inflammation in patients with ankylosing spondylitis by magnetic resonance imaging: a comparison between contrast enhanced T1 and short tau inversion recovery (STIR) sequences.

OBJECTIVES: To compare the performance of two different MRI sequences-T(1) weighted, fat saturated, spin echo after application of contrast medium, and short tau inversion recovery (STIR) sequences-to detect spinal inflammation in patients with ankylosing spondylitis (AS). METHODS: Both MRI sequences were performed in 38 patients with active AS and compared using the MRI activity scoring system, ASspiMRI-a. One vertebral unit (VU) was defined as the region between two virtual lines drawn through the middle of each vertebral body. RESULTS: Intraclass correlation coefficients were excellent-0.91 and 0.86 for the Gd-DTPA and STIR sequences, respectively. The overall correlation of the single MRI scores for both sequences was also good (r = 0.84, p = 0.01). The intrarater variance was 6.71 and 9.41 and the interrater variance was 13.16 and 19.04 for the Gd-DTPA and STIR sequences, respectively. The smallest detectable distance was 4.7 and 5.6 for the Gd-DTPA and STIR sequences, respectively. The concordance rate for both sequences was 83.5% (range 80.5-87.7% in the three spinal segments). Inflammatory spinal lesions were found in 10.1% of the VUs in the STIR sequence but not in the T(1)/Gd-DTPA sequence, while the T(1)/Gd-DTPA sequence showed inflammatory lesions in 6.4% of the VUs that were found normal by STIR. CONCLUSIONS: Both MRI techniques can evaluate active spinal lesions in patients with AS. More spinal lesions are detected by the STIR sequence, but the reliability between readings and readers is better for the Gd-DTPA sequence. The ASspiMRI-a is a reliable instrument for evaluating acute spinal changes in AS.

Acute Disease↗
PubMed2005

Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis before and after therapy with the tumor necrosis factor alpha receptor fusion protein etanercept.

OBJECTIVE: To assess spinal inflammation by magnetic resonance imaging (MRI) before and after treatment with the tumor necrosis factor receptor fusion protein etanercept compared with placebo. METHODS: As part of a recently published randomized, controlled trial, 40 patients with ankylosing spondylitis (AS) underwent MRI of the lower thoracic and lumbar spine at 4 different time points: baseline, 12 weeks, 24 weeks, and 48 weeks. Nineteen patients received subcutaneous etanercept twice weekly (25 mg twice daily) for 1 year, and 21 patients received placebo for 6 months before being switched to etanercept. The mean age of the patients was 39.7 years, 75% were male, 89% were HLA-B27 positive, and the mean disease duration was 13 years. MRI examinations included T1-weighted sequences before and after application of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) and T2-weighted fat-saturated sequences. MRI sequences were scored with an adjusted AS spinal MRI score, using predefined vertebral units (VUs) as a basis. RESULTS: After 12 weeks, spinal inflammation (as assessed by T2-weighted MRI with fat saturation) regressed by 54% in the etanercept group (mean score 1.33 per VU at baseline and 0.61 per VU at 12 weeks; P = 0.002) but worsened by 13% in the placebo group (0.94 at baseline and 1.06 at 12 weeks) (P < 0.001 between groups). After switching to etanercept, placebo patients improved similarly. T1-weighted Gd-DTPA MRI sequences performed equally well in detecting spinal changes. At baseline, >50% of all active lesions were detected in the thoracic spine. Deterioration of chronic changes was significant only in patients treated with placebo. CONCLUSION: Etanercept treatment of patients with active AS results in regression of spinal inflammation as assessed by spinal MRI. Inclusion of the thoracic spine in MRI examinations of patients with AS may be of particular importance.

Adult↗
PubMed2005

Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept.

OBJECTIVE: To estimate the incidence of anterior uveitis in patients with ankylosing spondylitis (AS) who underwent anti-tumor necrosis factor (anti-TNF) therapy, using data from recently performed trials. METHODS: Data from 4 placebo-controlled studies with anti-TNF agents in AS (2 with etanercept and 2 with infliximab) and 3 open-label studies were analyzed for the prestudy prevalence and the incidence of reported flares of anterior uveitis. RESULTS: A total of 717 patients who received treatment for anterior uveitis during the course of published clinical studies were identified by a systematic literature search using Medline. Followup information on the course of anterior uveitis was available for 397 patients. Of these, 297 were exposed to etanercept and 90 were exposed to infliximab for a total of 430 and 146.4 years, respectively. Among 190 patients who received placebo, the overall exposure was 70.5 years. The frequency of flares of anterior uveitis in the placebo group was 15.6 per 100 patient-years (95% confidence interval 7.8-27.9), while the patients treated with anti-TNF agents had a mean of only 6.8 anterior uveitis flares per 100 patient-years (P = 0.01). Flares of anterior uveitis occurred less frequently (although not significantly) in patients treated with infliximab than in patients treated with etanercept (3.4 per 100 patient-years and 7.9 per 100 patient-years, respectively). CONCLUSION: Treatment of AS patients with biologic agents directed against TNFalpha is associated with a significant decrease in the number of anterior uveitis flares. This reduction was slightly more marked among patients treated with infliximab, but the difference was not significant.

Antibodies, Monoclonal↗
PubMed2005

[Quality assurance of haemotherapy in anaesthesia. Auswertung eines 3-jahrigen Erfahrungszeitraums].

BACKGROUND: The measures for quality assurance in haemotherapy developed at the Charite Campus Mitte according to the transfusion law of 1998 are introduced and discussed. METHODS: In a 3-year study period the submission of transfusion documentation and the expiration of blood products were compared to the year 2001. The potentials for improvement for 2001-2003 were compared based on evaluation of the self-inspection documentation of the transfusion clinics. RESULTS: The submission rate for the transfusion documentation increased from 90% in 2001 to 98.3% in 2002 and 2003. The expiration of blood products decreased from 5.1% in 2001 to 1.7% in 2003 resulting in a cost reduction from 140,000 Euro to 50,000 Euro. Continuous need for improvement was found for the prescribed annual further education of staff on quality management. CONCLUSIONS: The self-inspection procedure in transfusion clinics still revealed potential for improvement, although documentation of transfusions were improved and the expiration of blood products and the resulting costs were substantially reduced.

Anesthesia↗
PubMed2005

No increase in rejection or graft loss in kidney transplant recipients with thrombophilia treated with anticoagulation and triple immunosuppression.

INTRODUCTION: Recent studies from Europe have demonstrated that patients with end-stage renal disease who receive a kidney transplant are at an increased risk for rejection and graft loss when compared with patients who have no known thrombophilia. The role of anticoagulation has not been investigated in these patients. MATERIALS AND METHODS: We prospectively tested patients who were evaluated for a kidney transplant for 8 thrombophilias, protein S and C deficiencies, factor V Leiden mutation, antithrombin III deficiency, anticardiolipin antibody, lupus anticoagulant, prothrombin gene mutation, and heparin-induced platelet antibody (HIPA). Patients with any identified thrombophilia received heparin or argatroban (for HIPA (+) patients) followed by coumadin for 1 year after transplantation. Triple therapy included cyclosporine, prednisone, and CellCept (Roche Pharmaceuticals, Nutley, NJ, USA). Sensitized, black, or repeat transplantation patients received induction with an interleukin (IL)-2 inhibitor. Data were collected in a retrospective manner. Rejection was biopsy-proven. RESULTS: Of the 112 transplant recipients who were tested for thrombophilia, 37 had 1 or more thrombophilia and 75 had no thrombophilia identified. Twenty-six patients received heparin and 11 received argatroban. There were no differences in recipient age, cold storage time, graft loss, HLA match, rejection episodes, 1-year graft survival, or serum creatinine level at 1 year. Significant differences were noted in posttransplantation bleeding, 35% versus 5%, and delayed graft function, 32% versus 15%, in patients with thrombophilia versus no thrombophilia, respectively. CONCLUSION: This is the first study to demonstrate that there is no increase in rejection or graft loss in kidney transplant recipients with thrombophilia when treated with anticoagulation and triple immunosuppression.

Anticoagulants↗
PubMed2005

[Early rehabilitation care in the hospital--definition and indication. Results of the expert group "Early Rehabilitation Care in the Hospital"].

As a result of the continuing development in recent medicine, and improvements of emergency services, an increasing number of patients are surviving serious disease and injury. This has increased the need for rehabilitation, starting already during the acute hospital stay. Early identification and rehabilitation may reduce overall costs and help patients to regain independence earlier. Since the eighties specialized early post-acute rehabilitation units have been increasingly implemented in German hospitals. With book 9 of the German Social Code (SGB IX) coming into effect in July 2001, early post-acute rehabilitation care in hospitals became accepted as a social right. However, the specifics of early rehabilitation care have not been defined. There is a lack of generally accepted indication criteria for early rehabilitation services. Similarly, the aims, objectives and methods need to be specified. It was the objective of a group of interested experts from different fields and backgrounds to achieve an interdisciplinary consensus in terms of conceptual definitions and terminology for all early rehabilitation care services in the acute hospital. The development of the definitions and criteria was achieved by using a modified Delphi-technique. By publishing this paper the group is providing information about its activities and results. Examples of typical cases from the various fields of early rehabilitation care were identified and described. Furthermore, the report points out a number of other problems in the area of early rehabilitation care, which have yet to be solved.

Persons with Disabilities↗
PubMed2005

Six months open label trial of leflunomide in active ankylosing spondylitis.

OBJECTIVE: To examine the potential therapeutic effects of leflunomide in patients with active AS in an open label study. PATIENTS AND METHODS: Twenty patients with AS fulfilling the 1984 modified New York criteria with a Bath AS Disease Activity Index (BASDAI) >3 were given leflunomide for 6 months. Clinical outcome assessments included disease activity (BASDAI), function (BASFI), metrology (BASMI), patient's and physician's global assessment, peripheral joint assessment, quality of life (SF-36), global pain, and CRP. Primary end point was a reduction of disease activity as measured by the BASDAI of >25% at 6 months. RESULTS: A BASDAI 25% improvement was noted in 5/20 (25%) patients and a BASDAI 50% improvement in 4/20 (20%) patients. The absolute BASDAI did not change significantly over the 6 month study (4.9 at baseline v 4.3 at week 24, p>0.05). Similarly, no significant change was found for the BASFI, BASMI, patient's and physician's global assessment, SF-36 mental component, and CRP. For the 10 patients with peripheral arthritis, the mean number of inflamed joints was significantly reduced from 1.7 at baseline to 0.9 at week 12 (p = 0.034) and 0.2 at week 24 (p = 0.039). CONCLUSION: In this open study of patients with active AS only those with peripheral arthritis improved significantly with leflunomide treatment. Axial symptoms did not improve.

Adult↗
PubMed2005

Seronegative spondyloarthropathies: to lump or split?

The advent of novel biological therapies for the treatment of rheumatic disease has renewed interest in the seronegative spondyloarthropathies (SpAs). International efforts are redefining disease classification and measures of disease activity, outcome, metrology, and imaging. However, opinion is divided between those who propose that the SpA group represents the same disease with variable expression (the "lumpers") and those who consider these to be separate diseases with shared clinical features (the "splitters"). This review presents the evidence for both approaches.

Arthritis, Psoriatic↗
PubMed2005

Very early spondyloarthritis: where the inflammation in the sacroiliac joints starts.

Involvement of the sacroiliac joints (SIJ) is a major and characteristic feature of the spondyloarthritides (SpA). In early ankylosing spondylitis and undifferentiated SpA (uSpA) sacroiliitis is the most common early clinical finding and the presumed first manifestation of the disease. Magnetic resonance imaging has proved useful for visualising inflammation in the SIJ in adults and children. Recently, initial localisation of the inflammation in the SIJ has been described in some detail, but it has not been completely defined to date--either in imaging or in histopathological studies. This is mainly owing to the lack of data in very early disease and the lack of follow up studies. Here we present a patient with early disease, which may augment our understanding of this stage of SpA.

Age of Onset↗
PubMed2004

Long-term efficacy and safety of etanercept after readministration in patients with active ankylosing spondylitis.

OBJECTIVES: Treatment of ankylosing spondylitis (AS) with the tumour necrosis factor alpha (TNF-alpha) receptor fusion protein etanercept has shown efficacy in patients with active disease in randomized controlled trials (RCTs) for limited periods. The objective of the study was to assess the long-term efficacy and safety of etanercept over 1 yr, including discontinuation and readministration. METHODS: In this 54-week open observational study, 26 AS patients received 25 mg etanercept subcutaneously twice weekly after several months of discontinuation following a 6-month RCT with the same agent. All patients who developed high disease activity after cessation of etanercept, defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) > or = 4 and pain > or = 4 on a numerical rating scale, entered the study. Standard assessment tools, such as the Bath Ankylosing Spondylitis functional index (BASFI), were used. An intention-to-treat (ITT) and a completer analysis were performed. The results were compared with the baseline values of the open study. RESULTS: Out of the initial 30 patients, 26 (87%) were eligible for the open extension study after a mean of about 27 weeks. At week 54, 23/26 patients (88%) were still on treatment with etanercept. The ITT analysis showed that 58% (95% confidence interval 39-74%) of the patients achieved a 50% improvement of BASDAI at week 54. According to the Assessments in Ankylosing Spondylitis working group criteria, 8/26 patients (31%) were in partial remission at week 54. Function, metrology and quality of life improved significantly. Only one patient had a serious adverse event that resulted in discontinuation. CONCLUSIONS: This study shows that treatment with etanercept is efficacious and safe after readministration over 1 yr in patients with active AS not taking DMARDs or steroids.

Adult↗
PubMed2004

Inflammation in ankylosing spondylitis: a systematic description of the extent and frequency of acute spinal changes using magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly used to detect inflammation in the spine of patients with ankylosing spondylitis (AS). OBJECTIVES: To detect differentially the presence and extent of inflammation in the three spinal segments of patients with AS by MRI. METHODS: In 38 patients with active AS, acute spinal lesions were assessed by T(1) weighted, gadolinium enhanced, spin echo MRI (T(1)/Gd-DTPA) and short tau inversion recovery (STIR) sequences. MRI was quantified by the validated scoring system ASspiMRI-a. Acute spinal lesions were detected in the whole spine and in each spinal segment. One vertebral unit (VU) was defined as the region between two virtual lines drawn through the middle of each vertebral body. RESULTS: A greater number of inflammatory spinal lesions were found by the STIR sequence than by Gd-DTPA: inflammation was present in 30.6% of the VUs as assessed by STIR, compared with 26.8% of the same VUs assessed by T(1)/Gd-DTPA. Inflammation was found more commonly in the thoracic spine (TS) than in the cervical (CS) or the lumbar spine (LS) with both techniques. When STIR was used, spinal inflammation in the CS, the TS, and LS was detected in 10/38 (26%), 28/38 (74%), and 9/38 (24%) patients, respectively. The VU T7/8 was found to be the VU most often affected by both techniques (27.8% by T(1)/Gd-DTPA and 34.5% by STIR). CONCLUSIONS: Spinal inflammation is a common manifestation in patients with AS, and appears more frequently in the TS. The scoring system ASspiMRI-a can be used for evaluation of acute spinal changes in AS.

Acute Disease↗
PubMed2004

Two year maintenance of efficacy and safety of infliximab in the treatment of ankylosing spondylitis.

OBJECTIVE: To obtain results of the second year extension of an original 3 month randomised, placebo controlled trial (and the 1 year extension study) assessing the use of infliximab, a monoclonal antibody to tumour necrosis factor alpha, for the treatment of patients with ankylosing spondylitis (AS). METHODS: Of the 54 patients with AS who completed the first year of the study, 52 continued to receive infliximab 5 mg/kg every 6 weeks up to week 102. The primary end point was the proportion of patients achieving at least 50% improvement from baseline in the Bath AS Disease Activity Index (BASDAI) at week 102. Other assessments included patient and physician global assessments, quality of life as assessed by Short Form-36, Bath AS Functional Index, Bath AS Metrology Index, and C reactive protein (CRP). RESULTS: Improvement in signs and symptoms of AS seen during the first year of the study was sustained during the second year. Forty nine patients (71% of 69 enrolled patients and 49/52 (94%) patients who started year 2) completed the study up to week 102. Thirty (58%) patients achieved at least 50% improvement from baseline in the BASDAI score at week 102. Scores for other efficacy assessments were similar at weeks 54 and 102. Median CRP levels remained low at weeks 54 and 102 (3.9 and 4.3 mg/l, respectively). Side effects during the second year of the study were similar to those of the first year of treatment with infliximab. CONCLUSIONS: Patients with AS treated for 2 years with infliximab 5 mg/kg exhibited a good and durable clinical response.

Adult↗
PubMed2004

The burden of ankylosing spondylitis and the cost-effectiveness of treatment with infliximab (Remicade).

OBJECTIVES: In the past, treatment options for ankylosing spondylitis (AS) have been limited, and the introduction of new treatments such as infliximab will have a noticeable impact on health-care budgets. The objective of this study was therefore to assess the current burden of the disease and estimate the cost-effectiveness of infliximab treatments. METHODS: A cross-sectional retrospective observational study of resource consumption and utility related to disease severity was performed in patients who had participated in a population survey between 1992 and 1994 at the University of Bath and patients regularly followed at the Royal National Hospital for Rheumatic Diseases in Bath for up to 9 years. Mean costs and utility were estimated using a regression model including age, gender, disease duration, disease activity and functional status, and disease development was expressed as annual progression of functional disability. Cost-effectiveness of infliximab was modelled using a 3-month placebo-controlled clinical trial with open 1-yr extension in 70 patients, over a total time frame of 2 yr. In the model, costs and utility controlled for disease severity and age from the observational study were assigned to individual patients. The effect of long-term treatment was evaluated in a hypothetical model over 30 yr. RESULTS: Fifty-seven per cent of patients answered the questionnaires. The mean age was 57 (s.d. 11.2) yr, 74% were male and mean disease duration was 30.2 (11.7) yr. Mean total costs were estimated at pound 6765 (s.d. pound 166). Indirect costs represented 57.9% and non-medical costs such as investments and informal care accounted for 16.5% of total costs. Mean utility was 0.67 (0.21). In the main model, mean costs for untreated patients are estimated at pound 25,128. For the infliximab group, mean costs (excluding treatment) are estimated at pound 17,240, a reduction of 31%. Thus, part of the treatment cost was offset by savings in other resources ( pound 7888), leaving an incremental cost of pound 6214. Treatment increased the number of quality-adjusted live years (QALYs) by 0.175 QALYs, leading to a cost per QALY gained of pound 35,400 for the first year of treatment. When treatment is assumed to continue for the full 2 yr, the cost per QALY is pound 32,800. When infliximab infusions are given every 8 weeks instead of every 6 weeks, the cost per QALY is reduced to pound 17,300. In the long-term model, the cost per QALY is estimated at pound 9600. CONCLUSIONS: Non-medical costs and production losses dominate costs in AS, and economic evaluation must therefore adopt a societal perspective. The cost of treatment with infliximab is partly offset by reductions in the cost of the disease and patients' quality of life is increased, leading to a cost per QALY gained in the vicinity of pound 30,000 to pound 40,000 in the short term, but potentially below pound 10,000 in the long term.

Antibodies, Monoclonal↗
PubMed2004

Biological therapies in the spondyloarthritides--the current state.

Therapeutic options for patients suffering from the more severe spondyloarthritides (SpA) have been rather limited in the last decades. Evidence is now accumulating that anti-tumour necrosis factor (TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published concerning more than 1000 patients with AS and PsA, this treatment seems to be even more effective than in rheumatoid arthritis (RA). The anti-TNFalpha agents currently available, infliximab (Remicade), etanercept (Enbrel) and adalimumab (Humira), are approved for the treatment of RA in the USA and Europe. The situation for SpA is different from RA because there is an unmet medical need, especially in AS, since no therapies with disease-modifying anti-rheumatic drugs (DMARDs) are available for severely affected patients, especially those with spinal disease. Thus, TNF blockers may even be considered a first-line treatment in a patient with active AS and PsA whose condition is not sufficiently controlled with non-steroidal anti-inflammatory drugs (NSAIDs) in the case of axial disease, and sulphasalazine or methotrexate in the case of peripheral arthritis. For infliximab, a dose of 5 mg/kg is required, and intervals of between 6 and 12 weeks are necessary to constantly suppress disease activity-also a major aim for long-term treatment. The standard dosage of etanercept is 2 x 25 mg subcutaneously per week. There are almost no studies yet on adalimumab (standard dose in RA, 20-40 mg subcutaneously every 1-2 weeks) in SpA. Infliximab and etanercept are now both approved for AS in Europe. The efficacy of etanercept was first demonstrated in PsA, and it is now approved for this indication in the USA and Europe. There is preliminary evidence that both agents also work in other SpA, such as undifferentiated SpA (uSpA). Studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term anti-TNF therapy and whether radiological progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. These can largely be prevented by appropriate screening. As it stands now, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.

Antirheumatic Agents↗
PubMed2004

Analysing chronic spinal changes in ankylosing spondylitis: a systematic comparison of conventional x rays with magnetic resonance imaging using established and new scoring systems.

OBJECTIVES: To compare conventional radiography and magnetic resonance imaging (MRI) for detection of chronic changes in the spine of patients with ankylosing spondylitis (AS). METHODS: Assessment of chronic lesions in conventional x rays and T1 weighted MRI turbo spin echo sequences was performed with the established x ray scores BASRI and SASSS, the new Berlin score, and the MRI scoring system ASspiMRI-c All images were read twice and "blindly" by two readers. One vertebral unit (VU) was defined as the region between two virtual lines drawn through the middle of each vertebra. Definite involvement was defined as a score > or =2 in a spinal segment. RESULTS: Thirty nine patients with AS were examined (25 (64%) male, mean age 40.9 years, 33/36 (92%) HLA-B27 positive). The Berlin score correlated with the BASRI (r = 0.73, p = 0.01). The ASspiMRI-c correlated well with the BASRI and the Berlin score (r = 0.66 and r = 0.51, respectively, p = 0.01). The Berlin x ray score showed that 12/35 (34.3%), 13/35 (37.1%), and 12/28 (31.6%) patients had definite involvement of the cervical spine (CS), thoracic spine (TS), and lumbar spine (LS), respectively. The ASspiMRI-c showed that 10/36 (27.8%), 21/36 (58.3%), and 9/35 (25.7%) patients had definite involvement of the CS, TS, and LS, respectively. Syndesmophytes were found in 14.4% of all VUs with 90% agreement between the SASSS and Berlin score. CONCLUSIONS: T1 weighted MRI can detect chronic lesions in AS. The two new scoring systems proved valid in comparison with established scoring systems and based on aspects of the OMERACT filter. The thoracic spine is most commonly affected in AS. This part of the spine is best assessed by MRI.

Adult↗
PubMed2004

In vivo 1H magnetic resonance spectroscopy of rat brain after valproate administration.

Previous studies have shown that valproate is detectable in vitro by 1H magnetic resonance spectroscopy (MRS) at 1.5 T, whereas in patients on valproate monotherapy, no significant dose-dependent valproate signal could be seen. To investigate whether an increased signal-to-noise ratio as provided by higher valproate doses and increased magnetic field strength would enable detection of valproate in vivo, six Wistar rats were examined using volume-selective 1H MRS at 2.34 T. The spectra were analyzed by fitting a linear superposition of the basis spectra of valproate, brain metabolites, and simulated lipid signals. The analysis revealed no significant signal contributions after valproate administration of up to 330 mg/kg body weight. To analyze how underlying mechanisms, such as potential drug interactions with macromolecules, may affect the valproate signal, additional in vitro spectra of valproate were measured before and after adding albumin. The spectra exhibited a strong decrease of the valproate signal with increasing albumin concentration. The results support the hypothesis that in vivo valproate is bound to a high degree to macromolecules and will therefore not be detectable by 1H MRS.

Animals↗
PubMed2004

Development and preselection of criteria for short term improvement after anti-TNF alpha treatment in ankylosing spondylitis.

OBJECTIVE: To develop and compare candidate improvement criteria for anti-TNFalpha treatment in ankylosing spondylitis with optimal discriminating capacity between treatment and placebo. METHODS: Data from two randomised controlled trials which included 99 patients treated with infliximab or etanercept were used to evaluate 50 candidate improvement criteria. These were developed on the basis of pain, patient's global assessment, function, morning stiffness, spinal mobility, and C reactive protein. Different levels of improvement in each domain (20-60%) were used to define Boolean type criteria. These criteria were compared with different percentages of improvement on the BASDAI and with modified ASAS improvement criteria. Bootstrap methods were applied to calculate 95% confidence intervals (CI) of the chi(2) test values to select the best candidate improvement criteria. RESULTS: The best performing improvement criteria were "20% improvement in five of six domains" (chi(2) = 31.9 (95% CI, 18.0 to 46.9)) with a low placebo response of 2.9% and a high response to infliximab of 67.7%; and "ASAS 40% improvement" (chi(2) = 26.5 (13.3 to 41.1)), with response to placebo of 5.7% and response to infliximab of 64.7%. The good discriminating capacity of the two improvement criteria was confirmed by the combined dataset of the infliximab and etanercept trial. CONCLUSIONS: The "five of six" improvement criterion has the advantage of including the objective domains spinal mobility and acute phase reactants, but requires only 20% improvement. The ASAS 40% improvement criterion has the advantage of setting a high threshold, but only in patient reported outcomes. The choice between these improvement criteria needs to be based on further validation from upcoming trials.

Adult↗