Two-year cost effectiveness between two gradual tapering strategies in rheumatoid arthritis: cost-utility analysis of the TARA trial.

OBJECTIVE: The aim of the current study was to evaluate the 2-year cost-utility ratio between tapering conventional synthetic disease-modifying antirheumatic drugs (csDMARD) first followed by the tumour necrosis factor (TNF)-inhibitor, or vice versa, in patients with rheumatoid arthritis (RA). METHODS: Two-year data of the Tapering strategies in Rheumatoid Arthritis trial were used. Patients with RA, who used both a csDMARD and a TNF-inhibitor and had a well-controlled disease (disease activity score ≤2.4 and swollen joint count≤1) for at least 3 months, were randomised into gradual tapering the csDMARD first followed by the TNF-inhibitor, or vice versa. Quality-adjusted life years (QALYs) were derived from the European Quality of life questionnaire with 5 dimensions. Healthcare and productivity costs were calculated with data from patient records and questionnaires. The incremental cost-effectiveness ratio and the incremental net monetary benefit were used to assess cost effectiveness between both tapering strategies. RESULTS: 94 patients started tapering their TNF-inhibitor first, while the other 95 tapered their csDMARD first. QALYs (SD) were, respectively, 1.64 (0.22) and 1.65 (0.22). Medication costs were significantly lower in the patients who tapered the TNF-inhibitor first, while indirect cost were higher due to more productivity loss (p=0.10). Therefore, total costs (SD) were €38 833 (€39 616) for tapering csDMARDs first, and €39 442 (€47 271) for tapering the TNF-inhibitor (p=0.88). For willingness-to-pay (WTP) levels <€83 800 tapering, the csDMARD first has the highest probability of being cost effective, while for WTP levels >€83 800 tapering the TNF-inhibitor first has the highest probability. CONCLUSION: Our economic evaluation shows that costs are similar for both tapering strategies. Regardless of the WTP, tapering either the TNF-inhibitor or the csDMARD first is equally cost effective. TRIAL REGISTRATION NUMBER: NTR2754.

Comparison of disease activity measures in early psoriatic arthritis in usual care.

OBJECTIVES: To compare responsiveness and longitudinal validity of Disease Activity Score 28 (DAS28), Disease Activity index for PSoriatic Arthritis (DAPSA), Composite Psoriatic Disease Activity Index (CPDAI), Psoriatic ArthritiS Disease Activity Score (PASDAS), GRAppa Composite scorE (GRACE) and Minimal Disease Activity (MDA) in usual care PsA patients, within 1 year after diagnosis. METHODS: Data collected in the Dutch southwest early PsA cohort (DEPAR) were used. Responsiveness was assessed using effect size (ES), standardized response mean (SRM), and discrimination between different general health states. Longitudinal validity was tested using mixed models with outcomes health-related quality of life (HRQOL), productivity and disability. RESULTS: Responsiveness was highest for PASDAS, with ES 1.00 and SRM 0.95, lowest for DAPSA, with ES 0.73 and SRM 0.71, and in between for DAS28, CPDAI and GRACE. Differences in general health were best discriminated with PASDAS and GRACE. Patients reporting stable or worsening general health could not be distinguished by DAS28 or CPDAI. Discrimination was better using DAPSA, but worse than when using PASDAS and GRACE. Longitudinal evolvement of HRQOL and productivity had the highest association with low disease activity according to GRACE, followed by PASDAS, MDA, DAPSA, DAS28, with the lowest association for CPDAI. CONCLUSION: PASDAS and GRACE were superior with respect to responsiveness, and together with MDA best related to longitudinal evolvement of HRQOL, productivity and disability. Responsiveness and longitudinal validity of most outcomes were inferior for DAS28, DAPSA and CPDAI. As alternatives to the continuous measure DAPSA, use of PASDAS or GRACE should be considered.

No clear association between ultrasound remission and health status in rheumatoid arthritis patients in clinical remission.

Objectives: Although RA patients achieve clinical remission, risk of flare still exists. Given the association between US synovitis and increased risk of flare, it is of clinical interest whether these patients report a different health status. Therefore, our aim was to evaluate the frequency of US remission in RA patients in clinical remission and to compare the health status of RA patients in clinical remission with those who were also in US remission. Methods: In a prospective study, we included 89 RA patients (aged >17 years) treated with a synthetic DMARD and a TNF inhibitor who were in remission (DAS in 44 joints ⩽2.4 and swollen joint count ⩽1). Demographic characteristics, swollen and tender joints, laboratory variables, US (MCP2-5, PIP2-5, wrists and MTP2-5) and patient-reported outcomes (general health, functional ability, fatigue, depression and anxiety, pain and morning stiffness) were recorded at two consecutive visits (3 months apart). US remission was defined as grey scale grade ⩽1 and power Doppler = 0. Results: At visit 1, 39% of patients were in US remission. At visit 2, 32% of patients were in US remission. At visit 1, functional ability (HAQ) was scored lower by patients in US remission (P = 0.029). At visit 2, HAQ scores were similar (P = 0.928). At visit 2, Hospital Anxiety and Depression Scale anxiety score and visual analog scale pain were significantly higher in patients in US remission. Similar levels were found for the other patient-reported outcomes. Conclusion: One-third of RA patients in clinical remission were in US remission. In our study population, we could not find a clear association between health status of RA patients and being in US remission.

Limited value for ultrasonography in predicting flare in rheumatoid arthritis patients with low disease activity stopping TNF inhibitors.

Objective: Ultrasonography (US) can be used for treatment decisions in RA patients. This study investigated the added value of US to clinical variables in predicting flare in RA patients with longstanding low disease activity when stopping TNF inhibitors (TNFi). Methods: Cox models with and without using US added to clinical variables were developed in the Potential Optimization of Expediency of TNFi-UltraSonography study. RA patients (n = 259), using >1 year TNFi and csDMARD with DAS28 < 3.2 for 6 months prior to inclusion, were followed for 52 weeks after stopping TNFi. The added value of US was assessed in two ways: first, by the extent to which individual predictions for flare at 52 weeks with and without US differed; and second, by comparing how US information improved the prediction to classify patients at 52 weeks in the low risk (<33% flare), intermediate risk (33-50%) and high risk (50-100%) groups. Results: Although US was predictive of flare at group level (multivariate hazard ratio = 1.7; 95% CI: 1.1, 2.5), individual predictions for flare at 52 weeks with and without US differed little (median difference 3.7%; interquartile range: -7.8 to 6.5%). With US, 15.9% of patients were designated low risk; without US, 14.6%. In fact, 12.0% of patients were US-classified as low risk with/without knowing US. Conclusion: In RA patients with longstanding low disease activity, at time of stopping TNFi, US is a predictor for flare at group level, but at the patient level, US has limited added value when common clinical parameters are used already, though the predictive value of clinical predictors is modest as well.

Do we need to lower the cut point of the 2010 ACR/EULAR classification criteria for diagnosing rheumatoid arthritis?

OBJECTIVE: In this study we aimed to evaluate the effect of lowering the cut point of the 2010 criteria to identify more patients with RA among early inflammatory arthritis patients. METHODS: We included early arthritis patients from the Rotterdam Early Arthritis Cohort with at least one joint with clinical synovitis and symptoms for <1 year, with no other explanation for their symptoms. The demographic and clinical characteristics of each patient were recorded at baseline. Patients were classified as case or non-case at the 1-year follow-up by the definition used in the development of the 2010 criteria (MTX initiation). To assess the diagnostic performance of the 2010 criteria, the sensitivity and specificity at each cut point were determined. RESULTS: We included 557 patients in our analysis. At the 1-year follow-up, 253 patients (45%) were classified as case (MTX use). In the group of patients who scored 0-5 points (n = 328), 98 patients (30%) were classified as case (MTX use). The sensitivity and specificity of the 2010 criteria using the cut point of 6 were 61% and 76%, respectively. With the cut point of 5, the sensitivity would increase to 76% and the specificity would decrease to 68%. CONCLUSION: By lowering the cut point of the 2010 criteria from 6 to 5 points, we were able to identify 15% more RA patients at the cost of 8% more false-positive patients.

Best cost-effectiveness and worker productivity with initial triple DMARD therapy compared with methotrexate monotherapy in early rheumatoid arthritis: cost-utility analysis of the tREACH trial.

OBJECTIVE: To evaluate direct and indirect costs per quality adjusted life year (QALY) for different initial treatment strategies in very early RA. METHODS: The 1-year data of the treatment in the Rotterdam Early Arthritis Cohort trial were used. Patients with a high probability (>70%) according to their likelihood of progressing to persistent arthritis, based on the prediction model of Visser, were randomized into one of following initial treatment strategies: (A) initial triple DMARD therapy (iTDT) with glucocorticoids (GCs) intramuscular (n = 91); (B) iTDT with an oral GC tapering scheme (n = 93); and (C) initial MTX monotherapy (iMM) with GCs similar to B (n = 97). Data on QALYs, measured with the Dutch EuroQol, and direct and indirect cost were used. Direct costs are costs of treatment and medical consumption, whereas indirect costs are costs due to loss of productivity. RESULTS: Average QALYs (sd) for A, B and C were, respectively, 0.75 (0.12), 0.75 (0.10) and 0.73 (0.13) for Dutch EuroQol. Highest total costs per QALY (sd) were, respectively, €12748 (€18767), €10 380 (€15 608) and €17 408 (€21 828) for strategy A, B and C (P = 0.012, B vs C). Direct as well as indirect costs were higher with iMM (strategy C) compared with iTDT (strategy B). Higher direct costs were due to ∼40% more biologic usage over time. Higher indirect costs, on the other hand, were caused by more long-term sickness and reduction in contract hours. iTDT was >95% cost-effective across all willingness-to-pay thresholds compared with iMM. CONCLUSION: iTDT was more cost-effective and had better worker productivity compared with iMM.

Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid arthritis.

OBJECTIVE: To investigate if erythrocyte-methotrexate-polyglutamate (MTX-PG) concentrations in patients with rheumatoid arthritis (RA) are associated with disease activity or adverse events. METHODS: We used a longitudinal study design with two cohorts. The derivation cohort included 102 and the validation cohort included 285 patients with RA on MTX. We measured erythrocyte-MTX-PG with 1-5 glutamate residues at 3 months, 6 months and 9 months after MTX start with a liquid chromatography (LC)-mass spectrometry (MS)/MS assay. Outcomes were disease activity score in 28 joints (DAS28) and adverse events. Longitudinal associations of MTX-PG concentrations after 3 months, 6 months and 9 months with DAS28 were tested with a linear mixed model adjusted for age, gender, baseline DAS28, MTX dose and comedication. RESULTS: In the derivation cohort, mean DAS28 decreased from 4.26 (SE=0.14) at baseline to 2.72 (SE=0.13) after 9 months. Thirty per cent of patients in the derivation cohort experienced more than three adverse events after 3 months, which decreased to 18% after 9 months. In the validation cohort, DAS28 and adverse events were comparable with the derivation cohort. In the derivation cohort, MTX-PG1 (ß=-0.005), MTX-PG2 (ß=-0.022), MTX-PG3 (ß=-0.007) and total MTX-PG (ß=-0.004) were associated (p<0.05) with lower DAS28 over 9 months. In the validation cohort, MTX-PG2 (ß=-0.015), MTX-PG3 (ß=-0.010), MTX-PG4 (ß=-0.008) and total MTX-PG (ß=-0.003) were associated with lower DAS28 over 9 months. None of the MTX-PGs was associated with adverse events. CONCLUSIONS: In this first longitudinal study, we showed that an increase in erythrocyte-MTX-PG concentration was associated with a decreased DAS28 over 9 months in two cohorts, and is therefore a potential tool for therapeutic drug monitoring of MTX in RA.

Association of Physical Activity and Medication with Enthesitis on Ultrasound in Psoriatic Arthritis.

OBJECTIVE: Enthesitis is a manifestation of psoriatic arthritis (PsA), but its symptoms are difficult to interpret clinically. We investigated the associations of ultrasonographic changes in entheses with clinical characteristics in patients with PsA, and compared enthesis changes of patients aged 35 to 60 years with healthy volunteers of that age. METHODS: Consecutive patients with PsA participated in this cross-sectional study, irrespective of enthesitis complaints and age. We collected data about complaints, physical activity and activity avoidance, medication, and clinical enthesitis. Inflammatory and structural enthesis changes were scored with the modified MAdrid Sonographic Enthesitis Index (MASEI). Among all patients, associations between ultrasound (US) scores and clinical characteristics were investigated using linear regression. We compared US scores of healthy volunteers and patients with PsA aged 35-60 years using Wilcoxon rank-sum tests. RESULTS: Eighty-four patients with PsA and 25 healthy volunteers participated. In patients with PsA, we found a small association between higher inflammatory-modified MASEI score and older age (ß 0.07, 95% CI 0-0.13) and current use of biologics (ß 1.56, 95% CI 0.16-2.95). Patients who reported avoiding activities had significantly lower inflammatory-modified MASEI scores (ß -1.71, 95% CI -3.1 to -0.32) than those who did not. The patients with PsA aged 35-60 years (n = 50) had similar inflammatory scores as healthy volunteers but higher structural scores (median 6 vs 2; p = 0.01). CONCLUSION: Within patients with PsA, avoiding physical activity, younger age, and not using biologics were associated with less enthesis inflammation. Patients with PsA and healthy volunteers aged 35 to 60 years displayed similar levels of inflammatory changes of the entheses, but patients had more structural damage.

Reduced Occurrence Rate of Acute Anterior Uveitis in Ankylosing Spondylitis Treated with Golimumab - The GO-EASY Study.

OBJECTIVE: Acute anterior uveitis (AAU) is common in ankylosing spondylitis (AS). Golimumab (GOL), a tumor necrosis factor-α inhibitor (TNFi), has proven to be effective in the treatment of AS. To date, the effect of GOL on the incidence of AAU in AS is unknown. The objective was to study the AAU occurrence rate in patients with AS during GOL treatment and secondarily, the efficacy of GOL in daily clinical practice. METHODS: The study was a multicenter prospective study in a real-world setting in patients with AS who were treated with GOL for 12 months. The occurrence of AAU was assessed in the year before the initial TNFi treatment and during GOL treatment and calculated for the period at risk for a new AAU. Measures for disease activity [Ankylosing Spondylitis Disease Activity Score (ASDAS)] and treatment response [Assessment of Spondyloarthritis international Society (ASAS20 score)] were collected. RESULTS: In total, 93 patients (65% male, 55% TNFi-naive, 27% history of AAU) were included, with a median disease duration of 7 years and ASDAS score of 3.1. During GOL treatment, the AAU occurrence rate was reduced from 11.1 to 2.2 per 100 patient-years (rate-ratio 0.20, 95% CI 0.04-0.91). After 3 months of treatment, 41% of the patients experienced a clinically important improvement of the ASDAS score (p < 0.001) and 36% an ASDAS20 response (p < 0.001). At month 12, 49% had achieved an ASAS20 response (p < 0.001). CONCLUSION: In AS, the AAU occurrence rate and disease activity decreased significantly during GOL treatment. Therefore, GOL can be considered a good choice in patients with AS who need a TNFi, especially in cases of recurrent AAU. (EudraCT number: 2012-002458-21).

Time to minimal disease activity in relation to quality of life, productivity, and radiographic damage 1 year after diagnosis in psoriatic arthritis.

BACKGROUND: In a cohort of patients with newly diagnosed psoriatic arthritis (PsA) who received usual care, we investigated the impact of time elapsed to minimal disease activity (MDA) on health-related quality of life (HRQoL), work productivity, and radiographic damage throughout the first year after diagnosis. METHODS: Data collected in the Dutch southwest early PsA cohort (DEPAR) study were analyzed. These three-monthly data encompassed disease activity, HRQOL was measured with the Short Form 36 (SF36) Physical Component Scale (SF36-PCS) and Mental Component Scale, and productivity was measured with the Productivity Cost Questionnaire. Radiographic damage was scored at baseline and at 12 months with the PsA-modified Sharp/van der Heijde score. Patients were classified by time to MDA as in early (within 3 months), late (at 6-12 months), and never MDA in the first year. RESULTS: We included 296 patients who had had their 1-year outpatient visit (mean age 51 years, 53% male). Ninety-six (32%) were classified as early MDA, 78 (26%) as late MDA, and 98 (33%) as never MDA. Data of 24 patients (8%) were missing. SF36-PCS and productivity scores improved after gaining MDA, but remained low in never MDA patients. At 1 year, SF36-PCS and productivity scores were similar in early and late MDA patients. Radiographic progression rate was low and similar in all groups. CONCLUSION: Gaining MDA was associated with considerable improvement in HRQoL and functioning, irrespective of time to first MDA. In the one third of patients not in MDA in the first year, the disease had a substantial health impact.