Construct validity of the PROMIS PF-10 in patients with inflammatory rheumatic diseases and severe limitations in physical functioning.

OBJECTIVE: Assessing the construct validity of the Patient-Reported Outcomes Measurement Information System Physical Function 10-Item Short Form (PROMIS PF-10) in a subpopulation of rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) patients with severe limitations in physical functioning (PF). METHOD: RA/axSpA patients with severe functional limitations completed the PROMIS PF-10, Health Assessment Questionnaire - Disability Index (HAQ-DI for RA) or Bath Ankylosing Spondylitis Functional Index (BASFI for axSpA), 36-item Short Form Health Survey (SF-36), EuroQol 5-dimensions 5-level (index score, EQ-VAS), and performed the Six-Minute Walk Test (6MWT). Construct validity was assessed by computing Spearman rank or Pearson correlation coefficients and testing hypotheses about correlations between the PROMIS PF-10 and measures of PF and quality of life. RESULTS: Data from 316 patients (180 RA/136 axSpA, 91.7%/47.8% female, mean ± sd age 58.6 ± 13.2/54.0 ± 11.3 years) were analysed. The median (IQR) PROMIS PF-10 score was 34.5 (31.4-37.6) in RA and 36.0 (32.8-38.3) in axSpA patients. The PROMIS PF-10 correlated strongly with the HAQ-DI, BASFI, and EQ-5D-5L index score (r > 0.6), moderately with the SF-36 Physical Component Summary score, EQ-VAS, and 6MWT (0.30 ≤ r ≤ 0.60), and weakly with the SF-36 Mental Component Summary score (r < 0.30). Five of six hypotheses (83%) were confirmed in both groups. CONCLUSION: The overall strong correlation of the PROMIS PF-10 with measures of PF and moderate to weak correlations with outcomes measuring different constructs were confirmed in subpopulations of RA and axSpA patients with severe functional limitations, supporting its construct validity.

Prospective Follow-Up of Cortical Interruptions, Bone Density, and Micro-structure Detected on HR-pQCT: A Study in Patients with Rheumatoid Arthritis and Healthy Subjects.

OBJECTIVES: The purpose of the study was to prospectively investigate change (repair or progression) in the number, surface area and volume of cortical interruptions, bone density (vBMD) and micro-structural parameters assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in finger joints of patients with rheumatoid arthritis (RA) treated with synthetic disease modifying anti-rheumatic drugs (sDMARDs) and/or biologic DMARDs (bDMARDs) over a 1-year follow-up period, and in comparison with healthy subjects (HS). METHODS: Thirty-two patients with RA (221 joints, 53% on bDMARDs) and 32 HS (117 joints) were assessed at baseline and after 1 year using semi-automatic analysis of HR-pQCT images. Mean changes (group level) and the proportion of joints (joint level) with changes beyond the least significant change were calculated. RESULTS: At baseline, 530 interruptions were identified in patients, and 136 in HS. The mean of the interruption parameters did not significantly change in either group Mean vBMD decreased more in patients than in HS (- 4.4 versus - 1.1 mgHA/cm3, respectively). In patients versus HS, proportionally more joints showed repair in interruption volume (6.6% versus 1.7%, respectively) and loss of vBMD (26.7% versus 12.9%, respectively). In patients on sDMARDs versus patients on bDMARDs, proportionally more joints showed progression in the number of interruptions and loss of vBMD (6.1% versus 1.8% and 31.3% versus 17.2%, respectively). CONCLUSIONS: HR-pQCT is able to quantify bone repair and progression. Cortical interruption-, vBMD-, and micro-structure were impaired in RA, of which vBMD and micro-structure further deteriorated, particularly in patients on sDMARDs.

An automated algorithm for the detection of cortical interruptions and its underlying loss of trabecular bone; a reproducibility study.

BACKGROUND: We developed a semi-automated algorithm that detects cortical interruptions in finger joints using high-resolution peripheral quantitative computed tomography (HR-pQCT), and extended it with trabecular void volume measurement. In this study we tested the reproducibility of the algorithm using scan/re-scan data. METHODS: Second and third metacarpophalangeal joints of 21 subjects (mean age 49 (SD 11) years, 17 early rheumatoid arthritis and 4 undifferentiated arthritis, all diagnosed < 1 year ago) were imaged twice by HR-pQCT on the same day with repositioning between scans. The images were analyzed twice by one operator (OP1) and once by an additional operator (OP2), who independently corrected the bone contours when necessary. The number, surface and volume of interruptions per joint were obtained. Intra- and inter-operator reliability and intra-operator reproducibility were determined by intra-class correlation coefficients (ICC). Intra-operator reproducibility errors were determined as the least significant change (LSCSD). RESULTS: Per joint, the mean number of interruptions was 3.1 (SD 3.6), mean interruption surface 4.2 (SD 7.2) mm2, and mean interruption volume 3.5 (SD 10.6) mm3 for OP1. Intra- and inter-operator reliability was excellent for the cortical interruption parameters (ICC ≥0.91), except good for the inter-operator reliability of the interruption surface (ICC = 0.70). The LSCSD per joint was 4.2 for the number of interruptions, 5.8 mm2 for interruption surface, and 3.2 mm3 for interruption volume. CONCLUSIONS: The algorithm was highly reproducible in the detection of cortical interruptions and their volume. Based on the LSC findings, the potential value of this algorithm for monitoring structural damage in the joints in early arthritis patients needs to be tested in clinical studies.

Structural damage and inflammation on radiographs or magnetic resonance imaging are associated with cortical interruptions on high-resolution peripheral quantitative computed tomography: a study in finger joints of patients with rheumatoid arthritis and healthy subjects.

OBJECTIVES: To study the relationship between structural damage and inflammatory features on magnetic resonance imaging (MRI) or radiography and other risk factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) seropositivity, hand dominance, disease duration] and the presence or number of cortical interruptions in finger joints on high-resolution peripheral quantitative computed tomography (HR-pQCT). METHOD: Finger joints of 38 healthy subjects and 39 patients with rheumatoid arthritis (RA) were examined through radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical interruptions. Descriptive statistics were calculated and associations examined using generalized estimating equations. RESULTS: Cortical interruptions were found in healthy subjects and patients with RA on HR-pQCT (mean ± sd 0.33 ± 0.63 vs 0.38 ± 0.64 per joint quadrant, respectively, p < 0.01). Structural damage on MRI (cortical interruptions) or radiographs (SvH ≥ 1) was associated with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95% confidence interval (CI) 7.5-21.4, p < 0.01 and OR 4.8, 95% CI 1.9-11.7, respectively, p < 0.01]. The presence of BMO or synovitis was associated with more cortical interruptions on HR-pQCT (ß 0.47, 95% CI 0.4-0.6, p < 0.01 and ß 1.9, 95% CI 0.6-3.1, p < 0.01). In patients with RA, ACPA, and/or RF seropositivity, hand dominance and disease duration were not associated with more cortical interruptions on HR-pQCT. CONCLUSION: Structural damage and inflammatory features on MRI and radiographs are associated with cortical interruptions on HR-pQCT. No association between other risk factors and cortical interruptions was demonstrated.

Vascular channels in metacarpophalangeal joints: a comparative histologic and high-resolution imaging study.

We evaluated whether cortical interruptions classified as vascular channel (VC) on high-resolution peripheral quantitative computed tomography (HR-pQCT) could be confirmed by histology. We subsequently evaluated the image characteristics of histologically identified VCs on matched single and multiplane HR-pQCT images. Four 3-mm thick portions in three anatomic metacarpophalangeal joint specimens were selected for histologic sectioning. First, VCs identified with HR-pQCT were examined for confirmation on histology. Second and independently, VCs identified by histology were matched to single and multiplane HR-pQCT images to assess for presence of cortical interruptions. Only one out of five cortical interruptions suggestive for VC on HR-pQCT could be confirmed on histology. In contrast, 52 VCs were identified by histology of which 39 (75%) could be classified as cortical interruption or periosteal excavation on matched single HR-pQCT slices. On multiplane HR-pQCT images, 11 (21%) showed a cortical interruption in at least two consecutive slices in two planes, 36 (69%) in at least one slice in two planes and five (10%) showed no cortical interruption. Substantially more VCs were present in histology sections than initially suggested by HR-pQCT. The small size and heterogeneous presentation, limit the identification as VC on HR-pQCT.

An automated algorithm for the detection of cortical interruptions on high resolution peripheral quantitative computed tomography images of finger joints.

OBJECTIVES: To introduce a fully-automated algorithm for the detection of small cortical interruptions (≥0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure). METHODS: Ten metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully- and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully- and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated. RESULTS: The median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully- and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and 6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi-automated procedure for both the number and surface of interruptions (ICC≥0.95) and the proportion of matching interruptions was high (≥76%). Also the inter-operator reliability was almost perfect (ICC≥0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring. CONCLUSION: The algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT.

The Reliability of a Semi-automated Algorithm for Detection of Cortical Interruptions in Finger Joints on High Resolution CT Compared to MicroCT.

We developed a semi-automated algorithm for the detection of cortical interruptions in finger joints using high-resolution peripheral quantitative computed tomography (HR-pQCT). Here, we tested its reliability compared to microCT (µCT) as gold standard. Nineteen joints of 10 female anatomic index fingers were imaged by HR-pQCT and µCT (82 and 18 µm isotropic voxel sizes, respectively). The algorithm was applied for detection of cortical interruptions of different minimum diameters (range >0.16 to >0.50 mm). Reliability was tested at the joint level with intra-class correlation coefficient (ICC) for the number of interruptions and interruption surface, and at the level of a single interruption for matching between HR-pQCT and µCT with a fixed interruption diameter (>0.10 mm) on µCT. The positive predictive value (PPV0.10mm) and sensitivity0.10mm were evaluated. The mean number of interruptions per joint depended on the diameter cut-off and ranged from 3.4 to 53.5 on HR-pQCT and from 1.8 to 45.1 on µCT for interruptions >0.50 to >0.16 mm, respectively. Reliability at the joint level was almost perfect (ICC ≥0.81) for both the number and surface of interruptions >0.16 and >0.33 mm. As expected, the PPV0.10mm increased with increasing interruption diameter from 84.9 to 100%, for interruptions >0.16 and >0.50 mm, respectively. However, the sensitivity0.10mm decreased with increasing interruption diameter from 62.4 to 4.7%. This semi-automated algorithm for HR-pQCT in finger joints performed best for the detection of cortical interruptions with a minimum diameter of >0.16 or >0.33 mm, showing almost perfect reliability at the joint level and interruptions matched with those on µCT.

Long-term efficiency of infliximab in patients with ankylosing spondylitis: real life data confirm the potential for dose reduction.

OBJECTIVE: To analyse the treatment outcome of patients with ankylosing spondylitis (AS) in the European AS infliximab cohort (EASIC) study after a total period of 8 years with specific focus on dosage and the duration of intervals between infliximab infusions. METHODS: EASIC included patients with AS who had received infliximab for 2 years as part of the ASSERT trial. After that period, rheumatologists were free to change the dose or the intervals of infliximab. Clinical data were status at baseline, end of ASSERT and for a total of 8 years of follow-up. RESULTS: Of the initially 71 patients with AS from EASIC, 55 patients (77.5%) had completed the 8th year of anti-tumour necrosis factor (TNF) treatment. Of those, 48 patients (87.3%) still continued on infliximab. The mean infusion interval increased slightly from 6 to 7.1±1.5 weeks, while 45.8% patients had increased the intervals up to a maximum of 12 weeks. The mean infliximab dose remained stable over time, with a minimum of 3.1 mg/kg and a maximum of 6.4 mg/kg. In patients receiving <5 mg/kg infliximab, the mean infusion interval increased to 7.0±1.2 weeks. In total, the mean cumulative dose per patient and per year decreased from 3566.30 to 2973.60 mg. CONCLUSIONS: We could observe that over a follow-up of 8 years of treatment with infliximab, >85% patients still remained on the same treatment, without any major safety events. Furthermore, both the infusion intervals and also the mean infliximab dose were modestly reduced in ≥70% of the patients without the loss of clinical efficiency.

Visual detection of cortical breaks in hand joints: reliability and validity of high-resolution peripheral quantitative CT compared to microCT.

BACKGROUND: To study the reliability and validity of high-resolution peripheral quantitative CT (HR-pQCT) with microCT (µCT) as gold standard in the visual detection of cortical breaks in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. METHODS: Ten cadaveric fingers (10 MCP and 9 PIP joints) were imaged by HR-pQCT and µCT and visually analyzed by two independent readers. Intra- and interreader reliability were evaluated for the presence (yes/no, kappa statistics) and the total number (intraclass correlation coefficient, ICC) of cortical breaks. Sensitivity, specificity, positive and negative predictive value (PPV respectively NPV) of HR-pQCT in detecting cortical breaks were calculated. RESULTS: With HR-pQCT, mean 149 cortical breaks were identified and with µCT mean 129 (p < 0.05). Intrareader reliability for the presence of a cortical break per quadrant was 0.52 (95 % CI 0.48-0.56) and 0.71 (95 % CI 0.67-0.75) for HR-pQCT and µCT, respectively, and for the total number of cortical breaks 0.61 (95 % CI 0.49-0.70) and 0.75 (95 % CI 0.68-0.82). Interreader reliability for the presence of a cortical break per quadrant was 0.37 (95 % CI 0.33-0.41) and 0.45 (95 % CI 0.41-0.49) for HR-pQCT and µCT, respectively, and for the number of cortical breaks 0.55 (95 % CI 0.43-0.65) and 0.54 (95 % CI 0.35-0.67). Sensitivity, specificity, PPV and NPV of HR-pQCT were 81.6, 64.0, 81.6, and 64 % respectively. CONCLUSION: Cortical breaks were commonly visualized in MCP and PIP joints with HR-pQCT and µCT. Reliability of both HR-pQCT and µCT was fair to moderate. HR-pQCT was highly sensitive to detect cortical breaks with µCT as gold standard.

Impact of Certolizumab Pegol on Patient-Reported Outcomes in Patients With Axial Spondyloarthritis.

OBJECTIVE: Patient-reported outcomes (PROs) provide an opportunity to collect important information relating to patient well-being, which is often difficult for physicians to measure (e.g., quality of life, pain, fatigue, and sleep). Here we evaluate the effects of certolizumab pegol (CZP) on PROs during the 24-week, double-blind phase of the RAPID axial spondyloarthritis (SpA) trial, a phase 3 trial of axial SpA patients, including both ankylosing spondylitis (AS) and nonradiographic axial SpA patients. METHODS: A total of 325 patients with active axial SpA were randomized 1:1:1 to placebo, CZP 200 mg every 2 weeks, or CZP 400 mg every 4 weeks. The primary end point was the Assessment of SpondyloArthritis International Society criteria for 20% improvement in disease activity response at week 12, and has been reported previously. PROs included total back pain, nocturnal back pain, a daily pain diary, the Sleep Problems Index II (SPI) domain of the Medical Outcomes Study (MOS) Sleep Scale, fatigue, the Ankylosing Spondylitis Quality of Life (ASQOL) measure, and the Short Form 36-item (SF-36) health survey physical component summary (PCS), mental component summary (MCS), and domains. RESULTS: Patients treated with CZP reported significant improvements from week 1 for nocturnal back pain (placebo -0.6, CZP 200 mg every 2 weeks -1.9, and CZP 400 mg every 4 weeks -1.6; P < 0.001) and ASQOL (placebo -1.0, CZP 200 mg every 2 weeks -2.3, and CZP 400 mg every 4 weeks -1.9; P < 0.05) compared with placebo, while significant improvements in total back pain were seen from day 2. Patients treated with both CZP dosing regimens also had significantly greater improvements in fatigue, MOS-SPI, SF-36 PCS, MCS, and domains compared with placebo. Improvements were similar in both AS and nonradiographic axial SpA patients. CONCLUSION: Both CZP dosing schedules rapidly improved patient well-being, as measured by PROs, including pain, fatigue, sleep, SF-36, and ASQOL in both AS and nonradiographic axial SpA patients.

Natural course of bone marrow oedema on magnetic resonance imaging of the sacroiliac joints in patients with early inflammatory back pain: a 2-year follow-up study.

OBJECTIVES: To describe the distribution and evolution over time of bone marrow oedema (BME) on magnetic resonance imaging of the sacroiliac joint (MRI-SIJ) in patients with recent-onset inflammatory back pain (IBP) suspected for axial spondyloarthritis (axSpA). METHOD: A 2-year follow-up study with annual MRI-SIJ was conducted in patients with IBP of duration ≤ 2 years. Each SIJ was divided into quadrants and MRI scores were analysed on a per-patient and per-SIJ quadrant basis. The presence of BME in each SIJ quadrant was recorded. Fulfilment of the Assessment of SpondyloArthritis international Society (ASAS) criteria for axSpA was assessed at baseline and at follow-up. RESULTS: At baseline, 68 patients (38% male; mean age 34.9 ± 10.3 years) were included. BME was visible at baseline in 24 (35%) patients, all fulfilling the ASAS axSpA criteria. Twenty-three of these 24 patients had a follow-up MRI. Not taking into account the baseline MRI, three (13%) of these 23 patients would no longer fulfil the ASAS criteria during follow-up because of subsiding BME. Forty-four (65%) patients had a negative baseline MRI, of whom 39 had a follow-up MRI available. New BME at follow-up meant that three (8%) of these 39 patients now fulfilled the ASAS criteria. At follow-up, baseline BME lesions subsided completely in 47% of SIJ quadrants (range 33-71%) whereas new BME lesions were detected in 8% of SIJ quadrants (range 2-11%). CONCLUSIONS: BME shows a fluctuating course in patients with early IBP suspected for axSpA. This may have an impact on diagnosis and the overall performance of the ASAS axSpA criteria.

Gadolinium contrast-enhanced MRI sequence does not have an incremental value in the assessment of sacroiliitis in patients with early inflammatory back pain by using MRI in combination with pelvic radiographs: a 2-year follow-up study.

OBJECTIVES: To evaluate the potential incremental value in detecting sacroiliitis of the T1 post-gadolinium diethylenetriaminepenta-acetic acid (Gd-DTPA) MRI sequence of the sacroiliac joints (SIJ) compared with the combination of short tau inversion recovery (STIR) MRI sequence and pelvic radiographs in patients with inflammatory back pain (IBP) suspected for axial spondyloarthritis. METHODS: A 2-year follow-up study was conducted in patients with IBP of less than 2 years duration. Annual MRI of the SIJ (MRI-SIJ) was performed and scored for bone marrow oedema (BME). Pelvic radiographs were scored according to the modified New York (mNY) criteria. Agreement on the presence of BME detected by the STIR and post-Gd-DTPA sequence and the incremental value of post-Gd-DTPA sequence over STIR plus radiographs was analysed by descriptive methods and kappa statistics. RESULTS: At baseline, 20 (29%) out of 68 patients (38% male; mean (SD) age 34.9 (10.3) years) enrolled had BME both on the STIR and post-Gd-DTPA sequences; 4 patients (6%) on the STIR sequence only; none on the post-Gd-DTPA sequence only (kappa value: 0.87). Fifteen (22%) patients fulfilled the mNY criteria at baseline. Sixty-two (91%) patients had at least 1 follow-up MRI-SIJ. At 2-year follow-up, 2 patients had BME on the post-Gd-DTPA sequence without BME on the STIR sequence. These 2 patients already fulfilled the mNY criteria at baseline. CONCLUSIONS: In this cohort of patients with early IBP, the post-Gd-DTPA sequence of the MRI-SIJ did not have an incremental value in the detection of sacroiliitis compared with the STIR sequence plus pelvic radiographs.

HLA-B27 and gender independently determine the likelihood of a positive MRI of the sacroiliac joints in patients with early inflammatory back pain: a 2-year MRI follow-up study.

OBJECTIVES: To describe how inflammation on MRI of the sacroiliac joints in patients with recent-onset inflammatory back pain (IBP) evolves over time, and to study determinants of activity on MRI of the sacroiliac joint. METHODS: A 2-year follow-up study with annual MRI of the sacroiliac joints was conducted in patients with IBP of less than 2 years' duration. Images were scored for bone marrow oedema on short τ inversion recovery and enhancement after administration of gadolinium on T1. RESULTS: Of the 68 patients (38% male; mean age 34.9 ± 10.3 years) enrolled, 44 had a negative baseline MRI. Of these 44 patients, 39 patients had at least one follow-up MRI of whom six patients (15%) developed activity on MRI during follow-up. 24 patients (35%) had an abnormal MRI at baseline. In 23 of these 24 patients follow-up MRI was available. The MRI became negative in seven of these 23 patients (30%) during follow-up. Human leucocyte antigen B27 (HLA-B27) positivity and male gender determined independently the likelihood of a positive MRI at any time point. In an HLA-B27-positive patient the likelihood of a positive MRI during follow-up is 88% if the baseline MRI is positive and 27% if the baseline MRI is negative. In an HLA-B27-negative patient with a negative MRI at baseline the likelihood of a positive MRI during follow-up is less than 5%. CONCLUSIONS: A positive MRI at baseline predicts a positive MRI during follow-up in HLA-B27-positive patients. A negative MRI at baseline in HLA-B27-negative patients strongly predicts a negative MRI during follow-up.

Nodular vasculitis in systemic lupus erythematosus.

A 42-year-old man presented with fever, photosensitivity, headaches, myalgia, hyperhidrosis, muscle weakness, alopecia, nasal crustae, weight loss, painful nails, arthritis, oral ulcers, erythema, discoid cutaneous lesions, and painful subcutaneous nodes. We made a diagnosis of systemic lupus erythematosus (SLE), type II cryoglobulinemia, and nodular vasculitis. In the skin, different types of vasculitis may be observed. Typically, histology shows leukocytoclastic vasculitis of superficial vessels both in SLE and mixed cryoglobulinemia, which clinically results in palpable purpura. In our patient, however, histopathological examination of the subcutaneous nodes not only revealed leukocytoclastic vasculitis of the superficial vasculature but also showed even more extensive involvement of dermal and subdermal small and medium sized vessels, giving rise to a nodular vasculitis.

Willingness of patients with ankylosing spondylitis to pay for inpatient treatment is influenced by the treatment environment and expectations of improvement.

OBJECTIVE: To assess the willingness to pay (WTP) for treatment in a spa resort of patients with ankylosing spondylitis (AS) and to assess if the experience of a spa influences the WTP. METHODS: 120 patients participating in a randomised trial comparing 3 weeks' treatment in a spa resort in Austria or in the Netherlands with a control group completed a WTP questionnaire before and after spa treatment. Patients indicated on a payment card the maximal co-payment they wanted to contribute for three scenarios that included (a) two levels of improvement in pain and stiffness and (b) two treatment environments: a rehabilitation hospital and a spa resort. RESULTS: At baseline, patients wanted to contribute more for the same improvement after treatment in a spa resort compared with a rehabilitation hospital (p<0.003), and were prepared to pay more when expected effects were higher (p<0.001). No differences were found between men and women, pain, or income. After the trial none of the treatment groups showed a change in their WTP. CONCLUSION: The WTP of patients with AS for inpatient treatment is influenced by the treatment environment and the expected improvement. Experiencing treatment in a spa resort does not influence the co-payment.

Measuring disease activity in ankylosing spondylitis: patient and physician have different perspectives.

OBJECTIVE: There is no "gold standard" to assess disease activity in patients with ankylosing spondylitis (AS). It is known that patients and physicians have different opinions about disease activity. The objective was therefore to investigate on which criteria patients with AS and physicians base their judgement on disease activity. METHODS: A cohort of 203 AS out-patients fulfilling the modified New York criteria included in the ongoing long-term follow-up was analysed. The Assessment in Ankylosing Spondylitis (ASAS) International Working Group has established different domains relevant for outcome in AS. Each domain includes a number of instruments for making assessments, and all these instruments are included in the Outcome in Ankylosing Spondylitis International Study and were made every 6 months for 2 yr. Disease activity from the patient perspective as well as from the physician perspective was analysed using the patient's or the physician's global assessment of disease activity [visual analogue scale (VAS): 0 (best)-10 (worst)] by dichotomizing into "high disease activity" (VAS > or = 6.0) and "low disease activity" (VAS < or = 4.0). Data reduction by principal components analysis (PCA) was performed to distinguish factors capturing correlated instruments. Discriminant analysis with the factor loadings was performed to discriminate between a low and a high disease activity state from both the patient's and the physician's perspective. Multiple regression analysis on the discriminant scores was performed to prioritize the instruments. RESULTS: PCA revealed four factors: spinal mobility, physician assessments, patient assessments and laboratory assessments (Cronbach's alpha 0.52-0.80; explained variance 61%). Discriminant function analysis showed that the factor "patient assessments" was most important (pooled correlation 0.85) in discriminating between a low and a high disease activity state as defined by the patient. The other three factors contributed marginally (pooled correlation <0.30). In contrast, the factors "physician's assessments" (pooled correlation 0.62), "spinal mobility" (pooled correlation 0.52) and "laboratory assessments" (pooled correlation 0.48) contributed most to the physician's perspective. The factor "patient assessments" did not contribute at all (pooled correlation 0.05). Multivariate analysis on the discriminant scores showed that the instruments "pain spine", "BASFI", "pain joints" and "BASDAI fatigue" explained more than 90% of variance in the case of the patient perspective. The instruments "cervical rotation", "swollen joint count", "CRP" and "intermalleolar distance" explained more than 90% of variance in case of physician perspective. CONCLUSION: AS patients rate disease activity on the basis of complaints while physicians rate disease activity on the basis of instruments related to disease severity and inflammation.

Large differences in cost of illness and wellbeing between patients with fibromyalgia, chronic low back pain, or ankylosing spondylitis.

OBJECTIVE: To compare the cost of illness of three musculoskeletal conditions in relation to general wellbeing. METHODS: Patients with fibromyalgia, chronic low back pain (CLBP), and ankylosing spondylitis who were referred to a specialist and participated in three randomised trials completed a cost diary for the duration of the study, comprising direct medical and non-medical resource utilisation and inability to perform paid and unpaid work. Patients rated perceived wellbeing (0-100) at baseline. Univariate differences in costs between the groups were estimated by bootstrapping. Regression analyses assessed which variables, in addition to the condition, contributed to costs and wellbeing. RESULTS: 70 patients with fibromyalgia, 110 with chronic low back pain, and 111 with ankylosing spondylitis provided data for the cost analyses. Average annual disease related total societal costs per patient were 7813 euro for fibromyalgia, 8533 euro for CLBP, and 3205 euro for ankylosing spondylitis. Total costs were higher for fibromyalgia and CLBP than for ankylosing spondylitis, mainly because of cost of formal and informal care, aids and adaptations, and work days lost. Wellbeing was lower in fibromyalgia (mean, 48) and low back pain (mean, 42) than in ankylosing spondylitis (mean, 67). No variables other than diagnostic group contributed to differences in costs or wellbeing. CONCLUSIONS: In patients under the care of a specialist, there were marked differences in costs and wellbeing between those with fibromyalgia or CLBP and those with ankylosing spondylitis. In particular, direct non-medical costs and productivity costs were higher in fibromyalgia and CLBP.