How do patients with systemic sclerosis experience currently provided healthcare and how should we measure its quality?

OBJECTIVES: To gain insight into SSc patients' perspective on quality of care and to survey their preferred quality indicators. METHODS: An online questionnaire about healthcare setting, perceived quality of care (CQ index) and quality indicators, was sent to 2093 patients from 13 Dutch hospitals. RESULTS: Six hundred and fifty patients (mean age 59 years, 75% women, 32% limited cutaneous SSc, 20% diffuse cutaneous SSc) completed the questionnaire. Mean time to diagnosis was 4.3 years (s.d. 6.9) and was longer in women compared with men (4.8 (s.d. 7.3) vs 2.5 (s.d. 5.0) years). Treatment took place in a SSc expert centre for 58%, regional centre for 29% or in both for 39% of patients. Thirteen percent of patients was not aware of whether their hospital was specialized in SSc. The perceived quality of care was rated with a mean score of 3.2 (s.d. 0.5) (range 1.0-4.0). There were no relevant differences between expert and regional centres. The three prioritized process indicators were: good patient-physician interaction (80%), structural multidisciplinary collaboration (46%) and receiving treatment according to SSc guidelines (44%). Absence of disease progression (66%), organ involvement (33%) and digital ulcers (27%) were the three highest rated outcome indicators. CONCLUSION: The perceived quality of care evaluated in our study was fair to good. No differences between expert and regional centres were observed. Our prioritized process and outcome indicators can be added to indicators suggested by SSc experts in earlier studies and can be used to evaluate the quality of care in SSc.

Validity and measurement precision of the PROMIS physical function item bank and a content validity-driven 20-item short form in rheumatoid arthritis compared with traditional measures.

OBJECTIVE: To evaluate the content validity and measurement properties of the Patient-Reported Outcome Measurement Information System (PROMIS) physical function item bank and a 20-item short form in patients with RA in comparison with the HAQ disability index (HAQ-DI) and 36-item Short Form Health Survey (SF-36) physical functioning scale (PF-10). METHODS: The content validity of the instruments was evaluated by linking their items to the International Classification of Functioning, Disability and Health (ICF) core set for RA. The measures were administered to 690 RA patients enrolled in the Dutch Rheumatoid Arthritis Monitoring registry. Measurement precision was evaluated using item response theory methods and construct validity was evaluated by correlating physical function scores with other clinical and patient-reported outcome measures. RESULTS: All 207 health concepts identified in the physical function measures referred to activities that are featured in the ICF. Twenty-three of 26 ICF RA core set domains are featured in the full PROMIS physical function item bank compared with 13 and 8 for the HAQ-DI and PF-10, respectively. As hypothesized, all three physical function instruments were highly intercorrelated (r 0.74-0.84), moderately correlated with disease activity measures (r 0.44-0.63) and weakly correlated with age (rs 0.07-0.14). Item response theory-based analysis revealed that a 20-item PROMIS physical function short form covered a wider range of physical function levels than the HAQ-DI or PF-10. CONCLUSION: The PROMIS physical function item bank demonstrated excellent measurement properties in RA. A content-driven 20-item short form may be a useful tool for assessing physical function in RA.

Green light may improve diagnostic accuracy of nailfold capillaroscopy with a simple digital videomicroscope.

Nailfold capillaroscopy is a non-invasive and safe technique for the analysis of microangiopathologies. Imaging quality of widely used simple videomicroscopes is poor. The use of green illumination instead of the commonly used white light may improve contrast. The aim of the study was to compare the effect of green illumination with white illumination, regarding capillary density, the number of microangiopathologies, and sensitivity and specificity for systemic sclerosis. Five rheumatologists have evaluated 80 images; 40 images acquired with green light, and 40 images acquired with white light. A larger number of microangiopathologies were found in images acquired with green light than in images acquired with white light. This results in slightly higher sensitivity with green light in comparison with white light, without reducing the specificity. These findings suggest that green instead of white illumination may facilitate evaluation of capillaroscopic images obtained with a low-cost digital videomicroscope.

Treating to the target of remission in early rheumatoid arthritis is cost-effective: results of the DREAM registry.

BACKGROUND: Where health economic studies are frequently performed using modelling, with input from randomized controlled trials and best guesses, we used real-life data to analyse the cost-effectiveness and cost-utility of a treatment strategy aiming to the target of remission compared to usual care in early rheumatoid arthritis (RA). METHODS: We used real-life data from comparable cohorts in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry: the DREAM remission induction cohort (treat-to-target, T2T) and the Nijmegen early RA inception cohort (usual care, UC). Both cohorts were followed prospectively using the DREAM registry methodology. All patients fulfilled the American College of Rheumatology criteria for RA and were included in the cohort at the time of diagnosis. The T2T cohort was treated according to a protocolised strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6). The UC cohort was treated without DAS28-guided treatment decisions. EuroQol-5D utility scores were estimated from the Health Assessment Questionnaire. A health care perspective was adopted and direct medical costs were collected. The incremental cost effectiveness ratio (ICER) per patient in remission and incremental cost utility ratio (ICUR) per quality-adjusted life year (QALY) gained were calculated over two and three years of follow-up. RESULTS: Two year data were available for 261 T2T patients and 213 UC patients; an extended follow-up of three years was available for 127 and 180 patients, respectively. T2T produced higher remission percentages and a larger gain in QALYs than UC. The ICER was € 3,591 per patient in remission after two years and T2T was dominant after three years. The ICUR was € 19,410 per QALY after two years and T2T was dominant after three years. CONCLUSIONS: We can conclude that treating to the target of remission in early RA is cost-effective compared with UC. The data suggest that in the third year, T2T becomes cost-saving.

Long-term effectiveness and safety of TNF-blocking agents in daily clinical practice: results from the Dutch Rheumatoid Arthritis Monitoring register.

OBJECTIVES: Experience with anti-TNF agents for a decade can be used to research the safety and effectiveness of anti-TNF agents in the long term. The objective of this article is to describe drug survival, disease activity, daily functioning, quality of life and adverse events of TNF-blocking agents in daily clinical practice after 5 years of follow-up. METHODS: Data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) register of 1560 RA patients were used for analyses (5-year follow-up, n=174). Drug survival and time to first serious infection or malignancy were analysed by Kaplan-Meier analysis. Several outcome measures at several follow-up moments were analysed per intention to treat and per protocol. RESULTS: The 5-year drug survival of the first anti-TNF was 45%, and 60% for total use of TNF-blocking agents. Baseline 28-joint DAS (DAS-28) was 5.1 (s.d. 1.3). After 5 years, the mean DAS-28 was 3.2 (s.d. 1.3) in all patients who had started with TNF-blocking agents and 2.9 (s.d. 1.1) in patients who were still on TNF-blocking agents. In the latter group, the HAQ score was 0.88 (s.d. 0.7) and the EuroQol five dimensions (EQ-5D) utility score was 0.7 (s.d. 0.2). Incidence rates of serious infections and malignancies were 2.9 and 0.6 per 100 patient-years, respectively. CONCLUSION: Five-year follow-up of RA patients treated with TNF-blocking agents showed a 60% drug survival accompanied by sustained low disease activity, normalized function and quality of life similar to that in the general population. The benefit to risk ratio for long-term TNF-blocking therapy remains favourable.

Determinants of engagement in face-to-face and online patient support groups.

BACKGROUND: Although peer-to-peer contact might empower patients in various ways, studies show that only a few patients actually engage in support groups. OBJECTIVE: The objective of our study was to explore factors that facilitate or impede engagement in face-to-face and online peer support, using the theory of planned behavior (TPB). METHODS: A questionnaire was completed by 679 patients being treated for arthritis, breast cancer, or fibromyalgia at two Dutch regional hospitals. RESULTS: Our results showed that only a minority of the patients engaged in organized forms of peer support. In total 10% (65/679) of the respondents had engaged in face-to-face meetings for patients in the past year. Only 4% (30/679) of the respondents had contact with peers via the Internet in the past year. Patients were more positive about face-to-face peer support than about online peer support (P < .001). In accordance with the TPB, having a more positive attitude (P < .01) and feeling more supported by people in the social environment (P < .001) increased the intention to participate in both kinds of peer support. In addition, perceived behavioral control (P = .01) influenced the intention to participate in online peer support. Nevertheless, the intention to engage in face-to-face and online peer support was only modestly predicted by the TPB variables (R(2) = .33 for face-to-face contact and R(2) = .26 for online contact). CONCLUSION: Although Health 2.0 Internet technology has significantly increased opportunities for having contact with fellow patients, only a minority seem to be interested in organized forms of peer contact (either online or face-to-face). Patients seem somewhat more positive about face-to-face contact than about online contact.

Ultra-low doses of rituximab for continued treatment of rheumatoid arthritis (REDO study): a randomised controlled non-inferiority trial.

BACKGROUND: Rituximab is an effective treatment for rheumatoid arthritis, given as either two doses of 1000 mg (2 weeks apart) every 6 months (the dose recommended by the US Food and Drug Administration and European Medicines Agency) or two doses of 500 mg (2 weeks apart) or one dose of 1000 mg (a standard low dose) every 6 months. Findings of several small uncontrolled studies suggest that doses lower than the recommended dose or standard low dose might be sufficient for maintenance treatment, potentially improving safety and reducing costs. Therefore, we aimed to compare the efficacy of ultra-low doses of rituximab (one dose of 500 mg or 200 mg) with a standard low dose of rituximab (one dose of 1000 mg) for patients with rheumatoid arthritis who respond to standard doses of rituximab. METHODS: The REDO study is a randomised, double-blind, non-inferiority trial done at five centres in the Netherlands. Adults (aged ≥18 years) with rheumatoid arthritis responding well to rituximab were randomly allocated (1:2:2) to receive intravenous rituximab as one dose of either 1000 mg, 500 mg, or 200 mg, respectively. Volumes of all doses were equal to achieve masking. Randomisation lists were computer-generated and stratified by rheumatoid factor or anti-citrullinated protein antibody status (positive or negative) and concomitant use of conventional synthetic disease modifying antirheumatic drugs (yes or no). The primary analysis was a per-protocol hierarchical testing procedure comparing ultra-low doses with a standard low dose (500 mg vs 1000 mg at 3 months, followed by 500 mg vs 1000 mg at 6 months, 200 mg vs 1000 mg at 3 months, and 200 mg vs 1000 mg at 6 months), using a non-inferiority margin of 0·60 on change from baseline in the 28-joint disease activity score based on C-reactive protein levels (DAS28-CRP). The study is registered at www.trialregister.nl, NTR6117. FINDINGS: Between Dec 15, 2016, and Sept 20, 2018, 142 patients were randomly allocated to either 1000 mg rituximab (n=29), 500 mg rituximab (n=58), or 200 mg rituximab (n=55). The 500 mg dose was non-inferior to 1000 mg at 3 months (mean change from baseline in DAS28-CRP, -0·07, 95% CI -0·41 to 0·27) but not at 6 months (0·29, -0·08 to 0·65). Because of the hierarchical testing procedure, non-inferiority could not be tested for the 200 mg dose. 13 patients had serious adverse events, three (10%) in the 1000 mg group, six (10%) in the 500 mg group, and four (7%) in the 200 mg group. The most frequently reported serious adverse events were cardiovascular. No deaths occurred during the study. A significantly lower incidence of infections was seen in the ultra-low-dose groups compared with the standard dose group (1·10 infections per patient-year with the 1000 mg dose vs 0·52 per patient-year with the 500 mg dose and 0·51 per patient-year with the 200 mg dose; rate ratio 0·47, 95% CI 0·21-0·83; p=0·013 for 500 mg vs 1000 mg; 0·44, 0·22-0·88; p=0·019 for 200 mg vs 1000 mg). INTERPRETATION: Our study did not show non-inferiority of ultra-low doses of rituximab for continued treatment of patients with rheumatoid arthritis. Nonetheless, in clinical practice, a strategy with an ultra-low dose of rituximab might be considered after evaluation of risks and benefits, although further studies are needed to establish non-inferiority. Further analyses and a 2-year observational extension are ongoing and should provide further insight into efficacy and safety. FUNDING: Menzis and Centraal Ziekenfonds.

Predictors of biologic-free disease control in patients with rheumatoid arthritis after stopping tumor necrosis factor inhibitor treatment.

BACKGROUND: The aim of this study was to identify predictors of prolonged disease control after discontinuation of tumor necrosis factor inhibitor (TNFi) treatment in patients with rheumatoid arthritis (RA). METHODS: Post-hoc analysis of 439 RA patients (67.3% rheumatoid factor positive) with longstanding RA in remission or with stable low disease activity, randomized to stopping TNFi treatment in the multicenter POET trial. Prolonged acceptable disease control was defined as not restarting TNFi treatment within 12 months after stopping. Baseline demographic and disease-related variables were included in univariate and multivariate logistic regression analysis for identifying predictors of relapse. RESULTS: One year after baseline, 220 patients (50.1%) had not restarted TNFi treatment. Use of an anti-TNF monoclonal antibody (versus a receptor antagonist, OR = 2.41; 95% CI: 1.58-3.67), ≤10 yrs. disease duration (OR = 2.15; 95% CI: 1.42-3.26) and low or moderate multi-biomarker disease activity (MBDA) scores (OR = 2.00; 95% CI: 1.10-3.64) at baseline were independently predictive of successful TNFi discontinuation (area under the receiver operating characteristic curve = 0.66; 95% CI: 0.61-0.71). Results were similar when using no physician-reported flare as the criterion. TNFi-free survival was significantly different for patient groups based on the number of predictors present, ranging from 21.4% of patients with no predictor present to 66.7% of patients with all three predictors present. CONCLUSION: Patients using an anti-TNF monoclonal antibody, with shorter disease duration and low or moderate baseline MBDA score are most likely to achieve prolonged disease control after TNFi discontinuation. TRIAL REGISTRATION: Netherlands Trial Register NTR3112, 21 October 2011.

Dermatological guidelines for monitoring methotrexate treatment reduce drug-survival compared to rheumatological guidelines.

BACKGROUND: Methotrexate (MTX) is widely used as disease modifying treatment for psoriasis and psoriatic arthritis (PsA). Rheumatological and dermatological guidelines to prevent MTX-induced adverse events diverge in the number and frequency of blood tests. These differences are not based on evidence indicating a higher risk for patients with psoriasis compared to PsA or rheumatic arthritis (RA). This raises the question if multiple testing increases safety, or results in false positive signals potentially leading to early withdrawal of an effective treatment. OBJECTIVE: Compare the effects of MTX monitoring strategies by rheumatologists and dermatologists regarding drug survival, reasons for withdrawal and safety. METHODS: Retrospective follow-up of all patients diagnosed with psoriasis by dermatologists or PsA by rheumatologists. Included were consecutive patients who started methotrexate (MTX) between 2006 and 2012 and had a scheduled follow-up by dermatologist or rheumatologist. Exclusions were: drug not started after the first prescription or incomplete availability of lab data. Data were extracted from electronic records: start and stop dates and dosing of MTX; treatment with folic acid and dose; reasons for withdrawal of MTX; numbers of blood sampling and types of laboratory tests performed for MTX safety; number of abnormal tests; occurrence of any serious adverse event (SAE). RESULTS: 190 Psoriasis and 196 PsA patients starting methotrexate (MTX) were included. Age and sex were comparable. PsA patients used higher initial and maximum doses of MTX and folic acid, but psoriasis patients had a higher frequency of abnormal laboratory results (0.14 vs 0.03 per treatment month, p<0.001), resulting in a striking difference in withdrawal of MTX for abnormal liver enzymes (15.8% vs 3.6%, p<0.001). In PsA patients MTX was withdrawn less frequently for ineffectiveness (15.8 vs 24.2%, p<0.05) leading to longer drug survival in the first course of treatment (37.4±30 vs 18.8±19.1 months). Repeated courses of MTX were more often prescribed by rheumatologists than by dermatologists. There were no significant differences in the occurrence of SAE (psoriasis 0.0041 vs PsA 0.0038 per treatment month) or death (1.6% vs 2.0%) between these groups. Hospital admissions related to infection were recorded in 6 (3.1%) PsA vs 4 (2.1%) psoriasis patients. CONCLUSION: Strict monitoring by dermatologists resulted in more abnormal findings, which reduced drug survival of MTX. The limited monitoring strategy by rheumatologists was not associated with more SAEs. Further research in other populations is needed to confirm whether reduced intensity of monitoring can optimize the use of MTX with sufficient long-term safety.

Multi-biomarker disease activity score as a predictor of disease relapse in patients with rheumatoid arthritis stopping TNF inhibitor treatment.

OBJECTIVE: Successfully stopping or reducing treatment for patients with rheumatoid arthritis (RA) in low disease activity (LDA) may improve cost-effectiveness of care. We evaluated the multi-biomarker disease activity (MBDA) score as a predictor of disease relapse after discontinuation of TNF inhibitor (TNFi) treatment. METHODS: 439 RA patients who were randomized to stop TNFi treatment in the POET study were analyzed post-hoc. Three indicators of disease relapse were assessed over 12 months: 1) restarting TNFi treatment, 2) escalation of any DMARD therapy and 3) physician-reported flare. MBDA score was assessed at baseline. Associations between MBDA score and disease relapse were examined using univariate analysis and multivariate logistic regression. RESULTS: At baseline, 50.1%, 35.3% and 14.6% of patients had low (<30), moderate (30-44) or high (>44) MBDA scores. Within 12 months, 49.9% of patients had restarted TNFi medication, 59.0% had escalation of any DMARD and 57.2% had ≥1 physician-reported flare. MBDA score was associated with each indicator of relapse. At least one indicator of relapse was observed in 59.5%, 68.4% and 81.3% of patients with low, moderate or high MBDA scores, respectively (P = 0.004). Adjusted for baseline DAS28-ESR, disease duration, BMI and erosions, high MBDA scores were associated with increased risk for restarting TNFi treatment (OR = 1.85, 95% CI 1.00-3.40), DMARD escalation (OR = 1.99, 95% CI 1.01-3.94) and physician-reported flare (OR = 2.00, 95% 1.06-3.77). CONCLUSION: For RA patients with stable LDA who stopped TNFi, a high baseline MBDA score was independently predictive of disease relapse within 12 months. The MBDA score may be useful for identifying patients at risk of relapse after TNFi discontinuation.

An Economic Evaluation of Stopping Versus Continuing Tumor Necrosis Factor Inhibitor Treatment in Rheumatoid Arthritis Patients With Disease Remission or Low Disease Activity: Results From a Pragmatic Open-Label Trial.

OBJECTIVE: To evaluate, from a societal perspective, the incremental cost-effectiveness of withdrawing tumor necrosis factor inhibitor (TNFi) treatment compared to continuation of these drugs within a 1-year, randomized trial among rheumatoid arthritis patients with longstanding, stable disease activity or remission. METHODS: Data were collected from a pragmatic, open-label trial. Cost-utility analysis was performed using the nonparametric bootstrapping method, and a cost-effectiveness acceptability curve was constructed using the net-monetary benefit framework, where a willingness-to-accept threshold (WTA) was defined as the minimal cost saved that a patient accepted for each quality-adjusted life year (QALY) lost. RESULTS: A total of 531 patients were randomized to the stop group and 286 patients to the continuation group. Withdrawal of TNFi treatment resulted in a >60% reduction of the total drug cost, but led to an increase of ∼30% in other health care expenditures. Compared to continuation, stopping TNFi resulted in a mean yearly cost saving of €7,133 (95% confidence interval [95% CI] €6,071, €8,234]) and was associated with a mean loss of QALYs of 0.02 (95% CI 0.002, 0.040). Mean saved cost per QALY lost and per extra flare incurred in the stop group compared to the continuation group was €368,269 (95% CI €155,132, €1,675,909) and €17,670 (95% CI €13,650, €22,721), respectively. At a WTA of €98,438 per QALY lost, the probability that stopping TNFi treatment is cost-effective was 100%. CONCLUSION: Although an official WTA is not defined, the mean saved cost of €368,269 per QALY lost seems acceptable in The Netherlands, given existing data on willingness to pay.

Feasibility of photoacoustic/ultrasound imaging of synovitis in finger joints using a point-of-care system.

We evaluate a portable ultrasound and photoacoustic imaging (PAI) system for the feasibility of a point-of-care assessment of clinically evident synovitis. Inflamed and non-inflamed proximal interphalangeal joints of 10 patients were examined and compared with joints from 7 healthy volunteers. PAI scans, ultrasound power Doppler (US-PD), and clinical examination were performed. We quantified the amount of photoacoustic (PA) signal using a region of interest (ROI) drawn over the hypertrophic joint space. PAI response was increased 4 to 10 fold when comparing inflamed with contralateral non-inflamed joints and with joints from healthy volunteers (p < 0.001 for both). US-PD and PAI were strongly correlated (Spearman's ρ = 0.64, with 95% CI: 0.42, 0.79). Hence, PAI using a compact handheld probe is capable of detecting clinically evident synovitis. This motivates further investigation into the predictive value of PAI, including multispectral PAI, with other established modalities such as US-PD or MRI.

Further Simplification of the Simple Erosion Narrowing Score With Item Response Theory Methodology.

OBJECTIVE: To further simplify the simple erosion narrowing score (SENS) by removing scored areas that contribute the least to its measurement precision according to analysis based on item response theory (IRT) and to compare the measurement performance of the simplified version to the original. METHODS: Baseline and 18-month data of the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial were modeled using longitudinal IRT methodology. Measurement precision was evaluated across different levels of structural damage. SENS was further simplified by omitting the least reliably scored areas. Discriminant validity of SENS and its simplification were studied by comparing their ability to differentiate between the COBRA and sulfasalazine arms. Responsiveness was studied by comparing standardized change scores between versions. RESULTS: SENS data showed good fit to the IRT model. Carpal and feet joints contributed the least statistical information to both erosion and joint space narrowing scores. Omitting the joints of the foot reduced measurement precision for the erosion score in cases with below-average levels of structural damage (relative efficiency compared with the original version ranged 35-59%). Omitting the carpal joints had minimal effect on precision (relative efficiency range 77-88%). Responsiveness of a simplified SENS without carpal joints closely approximated the original version (i.e., all Δ standardized change scores were ≤0.06). Discriminant validity was also similar between versions for both the erosion score (relative efficiency = 97%) and the SENS total score (relative efficiency = 84%). CONCLUSION: Our results show that the carpal joints may be omitted from the SENS without notable repercussion for its measurement performance.

Validation of automatic joint space width measurements in hand radiographs in rheumatoid arthritis.

Computerized methods promise quick, objective, and sensitive tools to quantify progression of radiological damage in rheumatoid arthritis (RA). Measurement of joint space width (JSW) in finger and wrist joints with these systems performed comparable to the Sharp-van der Heijde score (SHS). A next step toward clinical use, validation of precision and accuracy in hand joints with minimal damage, is described with a close scrutiny of sources of error. A recently developed system to measure metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints was validated in consecutive hand images of RA patients. To assess the impact of image acquisition, measurements on radiographs from a multicenter trial and from a recent prospective cohort in a single hospital were compared. Precision of the system was tested by comparing the joint space in mm in pairs of subsequent images with a short interval without progression of SHS. In case of incorrect measurements, the source of error was analyzed with a review by human experts. Accuracy was assessed by comparison with reported measurements with other systems. In the two series of radiographs, the system could automatically locate and measure 1003/1088 (92.2%) and 1143/1200 (95.3%) individual joints, respectively. In joints with a normal SHS, the average (SD) size of MCP joints was [Formula: see text] and [Formula: see text] in the two series of radiographs, and of PIP joints [Formula: see text] and [Formula: see text]. The difference in JSW between two serial radiographs with an interval of 6 to 12 months and unchanged SHS was [Formula: see text], indicating very good precision. Errors occurred more often in radiographs from the multicenter cohort than in a more recent series from a single hospital. Detailed analysis of the 55/1125 (4.9%) measurements that had a discrepant paired measurement revealed that variation in the process of image acquisition (exposure in 15% and repositioning in 57%) was a more frequent source of error than incorrect delineation by the software (25%). Various steps in the validation of an automated measurement system for JSW of MCP and PIP joints are described. The use of serial radiographs from different sources, with a short interval and limited damage, is helpful to detect sources of error. Image acquisition, in particular repositioning, is a dominant source of error.

Stopping Tumor Necrosis Factor Inhibitor Treatment in Patients With Established Rheumatoid Arthritis in Remission or With Stable Low Disease Activity: A Pragmatic Multicenter, Open-Label Randomized Controlled Trial.

OBJECTIVE: Tumor necrosis factor inhibitor (TNFi) biologic agents are an effective treatment for rheumatoid arthritis (RA). It is unclear whether patients whose disease is in remission or who have stable low disease activity need to continue use of TNFi or can stop this treatment. This study was undertaken to assess whether patients with established RA who are in remission or have stable low disease activity can effectively and safely stop their TNFi therapy. METHODS: The study was designed as a pragmatic multicenter, open-label randomized controlled trial. Inclusion criteria were a diagnosis of RA according to the American College of Rheumatology 1987 classification criteria, as well as use of a TNFi for at least 1 year along with a stable dose of disease-modifying antirheumatic drugs and a Disease Activity Score in 28 joints (DAS28) of <3.2 over the 6 months preceding trial inclusion. Patients were randomized in a 2:1 ratio to either stop or continue treatment with their current TNFi. Flare was defined as a DAS28 of ≥3.2 during the 12-month follow-up period and an increase in score of ≥0.6 compared to the baseline DAS28. RESULTS: In total, 531 patients were allocated to the stop group and 286 to the TNFi continuation group. At 12 months, more patients had experienced a flare in the stop group (272 [51.2%] of 531) than in the continuation group (52 [18.2%] of 286; P < 0.001). The hazard ratio for occurrence of a flare after stopping TNFi was 3.50 (95% confidence interval [95% CI] 2.60-4.72). The mean DAS28 in the stop group was significantly higher during the follow-up period compared to that in the continuation group (P < 0.001). Of the 195 patients who restarted TNFi treatment after experiencing a flare and within 26 weeks after stopping, 165 (84.6%) had regained a DAS28 of <3.2 by 6 months later, and the median time to a regained DAS28 of <3.2 was 12 weeks (95% Cl 10.7-13.3). There were more hospitalizations in the stop group than in the continuation group (6.4% versus 2.4%). CONCLUSION: Stopping TNFi treatment results in substantially more flares than does continuation of TNFi in patients with established RA in remission or with stable low disease activity.

[Temporal arteritis: do not rely on the erythrocyte sedimentation rate]. / Arteriitis temporalis: vaar niet blind op de bloedbezinking.

Three patients with signs of temporal arteritis are presented. In two patients a normal ESR resulted in the diagnosis 'temporal arteritis' being discarded, prompting clinicians to consider meningitis, sinusitis, and blindness due to atherosclerosis. In the third case, the ESR measured with the Alifax Test-1TH apparatus was 17 mm/h, whereas the Westergren method used on the same sample resulted in an ESR of 83 mm/h. In all three cases CRP was elevated. On the basis of literature on the sensitivity of ESR and CRP it is advisable to use both measures when temporal arteritis is being considered. It is noted that in one hospital using the Alifax Test-1TH, only 52% of 25 patients with biopsy-proven temporal arteritis had an ESR over 40 mm/h, while 96% had elevated CRP. This observation requires further evaluation. The significance of signs, symptoms and new imaging techniques for recognising cranial giant cell arteritis is summarised.

Initial results of finger imaging using photoacoustic computed tomography.

We present a photoacoustic computed tomography investigation on a healthy human finger, to image blood vessels with a focus on vascularity across the interphalangeal joints. The cross-sectional images were acquired using an imager specifically developed for this purpose. The images show rich detail of the digital blood vessels with diameters between 100 µm and 1.5 mm in various orientations and at various depths. Different vascular layers in the skin including the subpapillary plexus could also be visualized. Acoustic reflections on the finger bone of photoacoustic signals from skin were visible in sequential slice images along the finger except at the location of the joint gaps. Not unexpectedly, the healthy synovial membrane at the joint gaps was not detected due to its small size and normal vascularization. Future research will concentrate on studying digits afflicted with rheumatoid arthritis to detect the inflamed synovium with its heightened vascularization, whose characteristics are potential markers for disease activity.

Adherence to a treat-to-target strategy in early rheumatoid arthritis: results of the DREAM remission induction cohort.

INTRODUCTION: Clinical trials have demonstrated that treatment-to-target (T2T) is effective in achieving remission in early rheumatoid arthritis (RA). However, the concept of T2T has not been fully implemented yet and the question is whether a T2T strategy is feasible in daily clinical practice. The objective of the study was to evaluate the adherence to a T2T strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6) in early RA in daily practice. The recommendations regarding T2T included regular assessment of the DAS28 and advice regarding DAS28-driven treatment adjustments. METHODS: A medical chart review was performed among a random sample of 100 RA patients of the DREAM remission induction cohort. At all scheduled visits, it was determined whether the clinical decisions were compliant to the T2T recommendations. RESULTS: The 100 patients contributed to a total of 1,115 visits. The DAS28 was available in 97.9% (1,092/1,115) of the visits, of which the DAS28 was assessed at a frequency of at least every three months in 88.3% (964/1,092). Adherence to the treatment advice was observed in 69.3% (757/1,092) of the visits. In case of non-adherence when remission was present (19.5%, 108/553), most frequently medication was tapered off or discontinued when it should have been continued (7.2%, 40/553) or treatment was continued when it should have been tapered off or discontinued (6.2%, 34/553). In case of non-adherence when remission was absent (42.1%, 227/539), most frequently medication was not intensified when an intensification step should have been taken (34.9%, 188/539). The main reason for non-adherence was discordance between disease activity status according to the rheumatologist and DAS28. CONCLUSIONS: The recommendations regarding T2T were successfully implemented and high adherence was observed. This demonstrates that a T2T strategy is feasible in RA in daily clinical practice.

Automated measurement of joint space width in small joints of patients with rheumatoid arthritis.

OBJECTIVE: Comparison of performances of 5 (semi)automated methods in measuring joint space width (JSW) in rheumatoid arthritis. METHODS: Change in JSW was determined by 5 measurement methods on 4 radiographs per patient from 107 patients included in the COBRA trial (comparing sulfasalazine alone or in combination with methotrexate and corticosteroids). For each method the number of patients with sufficient available results was assessed (efficiency). An independent repeated measurement was carried out on a random sample of 30 patients' baseline and 1-year radiographs, to evaluate within-method reliability of change scores. Discriminatory ability (DA) of the measurement methods (between the 2 treatment arms) was compared with the DA of the Sharp-van der Heijde score (SHS) and its 2 components (erosion and JSW scores). RESULTS: The overall success rate varied widely between methods. Applying the chosen threshold of a minimum of 50% available joints with a change score per patient resulted in a success rate > 92% in 4/5 methods. Repeatability of measurements was good for most methods (intraclass correlation coefficient > or = 0.80 in 4/5 methods). Almost all measurement methods in 3 followup periods (12/14) showed a lower mean loss of JSW in patients from the intensive treatment group, although this was rarely statistically significant, confirming the known difference in structural damage. JSW as measured by the (semi)automated systems often showed higher DA than the JSW score of the SHS, but was lower than the total SHS and erosion scores. CONCLUSION: Although efficiency of the methods should be improved further, results already show good reliability and encouraging DA of most methods. Optimal information may be obtained with a combination of scoring of erosions and (semi)automated measurement of JSW.