The susceptibility of attaining and maintaining DMARD-free remission in different (rheumatoid) arthritis phenotypes.

OBJECTIVES: To compare (sustained) DMARD-free remission rates((S)DFR), defined as respectively ≥6 months and >1 year, after 2 and 5 years between three clinical arthritis phenotypes; undifferentiated arthritis(UA), autoantibody-negative(RA-) and positive rheumatoid arthritis(RA+). METHODS: All UA(n = 130), RA-(n = 176) and RA + (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were used. (S)DFR comparisons between phenotypes after 2 and 5 years were performed with Logistic regression. Medication use and early and late flares(DAS ≥ 2.4), respectively defined as < 12 and >12 months after reaching DFR, were also compared. Cox proportional hazard models were used to evaluate potential predictors for (S)DFR. RESULTS: Within 2 and 5 years less DFR was seen in RA + (17.2-25.7%), followed by RA-(28.4-42.1%) and UA patients(43.1-58.5%). This also applied for SDFR within 2 and 5 years (respectively 7.6% and 21.4%; 20.5% and 38.1%; and 35.4% and 55.4%). A flare during tapering was seen in 22.7% of patients. Of the patients in DFR 7.5% had an early flare and 3.4% a late flare. Also more treatment intensifications occurred in RA+ compared with RA- and UA. We found that higher baseline DAS, ACPA positivity, BMI and smoking were negatively associated with (S)DFR, while clinical phenotype(reference RA+), short symptom duration(<6 months) and remission within 6 months were positively associated. CONCLUSIONS: (Long-term) clinical outcomes differ between undifferentiated arthritis, autoantibody-negative and positive rheumatoid arthritis(RA). These data reconfirm that RA can be subdivided into aforementioned clinical phenotypes and that treatment might be stratified upon these phenotypes, although validation is needed. TRIAL REGISTRATION: ISRCTN, https://www.isrctn.com/, ISRCTN26791028.

The impact of different (rheumatoid) arthritis phenotypes on patients' lives.

OBJECTIVES: To compare patient-reported outcome (PRO) domains between three arthritis phenotypes [undifferentiated arthritis (UA), autoantibody-negative RA (RA-) and autoantibody-positive RA (RA+)] at diagnosis, after 2 years and over time. METHODS: All UA (n = 130), RA- (n = 176) and RA+ (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were used. PRO comparisons between phenotypes at baseline and after 2 years were performed with analysis of variance, while a linear mixed model compared them over time. Effect sizes were weighted against the minimal clinically important differences (MCIDs) for each PRO. RESULTS: RA- patients had a higher disease burden compared with RA+ and UA. At baseline and after 2 years, RA- patients had more functional impairment and a poorer Physical Component Summary (PCS) compared with the other phenotypes, while they only scored worse for general health and morning stiffness duration at baseline. The MCIDs were exceeded at baseline, except for functional ability between RA+ and UA, while after 2 years only the MCID of the PCS was exceeded by RA- compared with UA and RA. After 2 years the PROs of all phenotypes improved, but PROs measuring functioning were still worse compared with the general population, even when patients had low disease activity. CONCLUSION: RA- patients had the highest disease burden of all phenotypes. Although most patients have low disease activity after treatment, all clinical phenotypes still have a similar significant impact on patients' lives, which is mainly physical. Therefore it is important to assess and address PROs in daily practice because of persistent disease burden despite low disease activity. TRIAL REGISTRATION: ISRCTN26791028.

Meta-Analyses on the Effects of Disease-Modifying Antirheumatic Drugs on the Most Relevant Patient-Reported Outcome Domains in Rheumatoid Arthritis.

OBJECTIVE: Whereas in the treatment of rheumatoid arthritis much evidence exists on the effects of current pharmacologic treatment on clinical outcomes, little is known about the effects on patient-reported outcomes. This systematic review aims to evaluate the effects of disease-modifying antirheumatic drugs (DMARDs) on the patient-relevant domains of pain, fatigue, activity limitation, overall emotional and physical health impact, and work/school/housework ability and productivity. METHODS: A literature search was conducted to identify randomized controlled trials wherein registered DMARDs were compared with placebo or methotrexate and reported the effects on patient-reported outcomes included in the International Consortium of Health Outcomes Measurement standard set for inflammatory arthritis. Random effects meta-analyses using the standardized mean differences of change scores as the effect measure were performed for the domains of pain, fatigue, and activity limitation, comparing DMARDs with placebo and methotrexate. The other 2 domains were presented narratively. RESULTS: Across the 5 domains, 69 records belonging to 52 studies were identified. All meta-analyses showed a decrease of burden when DMARDs were compared with placebo (standardized mean differences [95% confidence interval] in pain -0.80 [-0.99, -0.61], fatigue -0.48 [-0.64, -0.32], and activity limitation -0.56 [- 0.63, -0.49]) and when compared with methotrexate (-0.55 [-0.70, -0.41), -0.44 [-0.55, -0.33], and - 0.37 [-0.44, -0.30], respectively). CONCLUSION: DMARDs decrease the burden in all the domains that are relevant to patients. Effect sizes may be influenced by DMARD type. Therefore, in the decision for rheumatoid arthritis treatment, patient-reported outcomes should be taken into account.

Diagnostic Performance and Clinical Utility of Referral Rules to Identify Primary Care Patients at Risk of an Inflammatory Rheumatic Disease.

OBJECTIVE: To determine the diagnostic performance and clinical utility of the Rotterdam Early Arthritis Cohort (REACH) and the Clinical Arthritis Rule (CARE) referral rules in an independent population of unselected patients from primary care. METHODS: This study consisted of adults who were suspected of the need for referral to a rheumatologist by their general practitioner. Diagnostic accuracy measures and a net benefit approach were used to compare both rules to usual care for recognizing inflammatory arthritis and inflammatory rheumatic diseases (IRDs). Using the least absolute shrinkage and selection operator method and cross-validation we created an optimal prediction rule for IRD. RESULTS: This study consisted of 250 patients, of whom 42 (17%) were diagnosed with inflammatory arthritis and 55 (22%) with an IRD 3 months after referral. Considering inflammatory arthritis, the area under the receiver operating characteristic curve (AUC) was 0.72 (95% confidence interval [95% CI] 0.64-0.80) for REACH and 0.82 (95% CI 0.75-0.88) for CARE. Considering IRD, the AUC was 0.66 (95% CI 0.58-0.74) for REACH and 0.76 (95% CI 0.69-0.83) for CARE. CARE was of highest clinical value when compared to usual care. The composite referral rule for IRD of 10 parameters included sex, age, joint features, acute onset of symptoms, physical limitations, and duration of symptoms (AUC 0.82 [95% CI 0.75-0.88]). CONCLUSION: Both validated rules have a net benefit in recognizing inflammatory arthritis as well as IRD compared to usual care, but CARE shows superiority over REACH. Although the composite referral rule indicates a greater diagnostic performance, external validation is needed.

Diagnostic performance of the ACR/EULAR 2010 criteria for rheumatoid arthritis and two diagnostic algorithms in an early arthritis clinic (REACH).

INTRODUCTION: An ACR/EULAR task force released new criteria to classify rheumatoid arthritis at an early stage. This study evaluates the diagnostic performance of these criteria and algorithms by van der Helm and Visser in REACH. METHODS: Patients with symptoms ≤12 months from REACH were used. Algorithms were tested on discrimination, calibration and diagnostic accuracy of proposed cut-points. Two patient sets were defined to test robustness; undifferentiated arthritis (UA) (n=231) and all patients including those without synovitis (n=513). The outcomes evaluated were methotrexate use and persistent disease at 12 months. RESULTS: In UA patients all algorithms had good areas under the curve 0.79, 95% CI 0.73 to 0.83 for the ACR/EULAR criteria, 0.80, 95% CI 0.74 to 0.87 for van der Helm and 0.83, 95% CI 0.77 to 0.88 for Visser. All calibrated well. Sensitivity and specificity were 0.74 and 0.66 for the ACR/EULAR criteria, 0.1 and 1.0 for van der Helm and 0.59 and 0.93 for Visser. Similar results were found in all patients indicating robustness. CONCLUSION: The ACR/EULAR 2010 criteria showed good diagnostic properties in an early arthritis cohort reflecting daily practice, as did the van der Helm and Visser algorithms. All were robust. To promote uniformity and comparability the ACR/EULAR 2010 criteria should be used in future diagnostic studies.

Is the frequent sonographic anechoic area distally in metacarpophalangeal joints a sign of arthritis?

In clinical practice, ultrasonography (US) often reveals, in the dorsal scan, a small anechoic area distally in both inflamed and clinically non-inflamed metacarpophalangeal joints. This "distal anechogenicity in the metacarpophalangeal joint" (DAEM) might thus be scored false positively as arthritis. We aimed to investigate whether the DAEM is a sign of arthritis. We evaluated the prevalence of DAEMs in 24 non-arthritic subjects. We then compared the dimensions of the DAEM in 10 non-arthritic subjects with a DAEM and 7 consecutive rheumatoid arthritis (RA) outpatients, using 2-D and 3-D ultrasound. Furthermore, we dissected two fresh-frozen postmortem hand specimens after US. A DAEM was observed in the metacarpophalangeal 2 (MCP2) joints of 54% of the 24 non-selected non-arthritic individuals; in none of those did the joint exhibit a power Doppler signal. A DAEM was observed in 86% of the 7 RA patients. Dimensions of DAEMs did not statistically significantly differ between these groups. At 3-D imaging and dissection, the DAEM was found to be an extension of the metacarpophalangeal joint capsule. In conclusion, DAEMs occur frequently and are not a sign of arthritis, but are distal joint recesses. This should be taken into account when using current sensitive ultrasonographic scoring systems grading arthritis.