Increase in axial spondyloarthritis diagnoses after the introduction of the ASAS criteria: a systematic review.

To explore the proportion of axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) diagnoses within all newly referred patients visiting rheumatology outpatient clinics. And more specifically, to analyze whether there is an effect of the introduction of the ASAS and CASPAR classification criteria for axSpA and PsA. We systematically searched Embase, Medline Ovid, Cochrane Central and Web of Science from database inception to November 2022. Articles that investigated new onsets of axSpA and PsA in adults from rheumatology clinics were included. In total, 170 out of 7139 studies were found eligible for full-text review, after which 33 unique studies were included. Seventeen studies reported new onsets of axSpA, and 20 studies of PsA. The pooled proportion of axSpA within all newly referred patients was 19% (95% CI 15-23%) and 18% (95% CI 14-22%) for PsA. The proportion of axSpA before 2009 was 3% (95% CI 0-6%) and increased up to 21% (95% CI 14-28%) after 2009. For PsA, limited data were available in order to analyze the proportions of PsA before 2006. Overall, heterogeneity was high (I2 > 95%, p < 0.001) that was most likely caused by geographical area, study design, setting and use of different referral strategies. The pooled proportion of axSpA and PsA among patients referred to the rheumatology outpatient clinic was 19 and 18%, respectively. Although the proportion of diagnosed axSpA patients seemed to increase after the introduction of the ASAS criteria, due to the large heterogeneity our findings should be interpreted with caution.

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.

Comparison of laser speckle contrast imaging with laser Doppler perfusion imaging for tissue perfusion measurement.

OBJECTIVE: Laser-based tissue perfusion monitoring techniques have been increasingly used in animal and human research to assess blood flow. However, these techniques use arbitrary units, and knowledge about their comparability is scarce. This study aimed to model the relationship between laser speckle contrast imaging (LSCI) and laser Doppler perfusion imaging (LDPI), for measuring tissue perfusion over a wide range of blood flux values. METHODS: Fifteen healthy volunteers (53% female, median age 29 [IQR 22-40] years) were enrolled in this study. We performed iontophoresis with sodium nitroprusside on the forearm to induce regional vasodilation to increase skin blood flux. Besides, a stepwise vascular occlusion was applied on the contralateral upper arm to reduce blood flux. Both techniques were compared using a linear mixed model analysis. RESULTS: Baseline blood flux values measured by LSCI were 33 ± 6.5 arbitrary unit (AU) (Coefficient of variation [CV] = 20%) and by LDPI 60 ± 11.5 AU (CV = 19%). At the end of the iontophoresis protocol, the regional blood flux increased to 724 ± 412% and 259 ± 87% of baseline measured by LDPI and LSCI, respectively. On the other hand, during the stepwise vascular occlusion test, the blood flux reduced to 212 ± 40% and 412 ± 177% of its baseline at LDPI and LSCI, respectively. A strong correlation was found between the LSCI and LDPI instruments at increased blood flux with respect to baseline skin blood flux; however, the correlation was weak at reduced blood flux with respect to baseline. DISCUSSION: LSCI and LDPI instruments are highly linear for blood flux higher than baseline skin blood flux; however, the correlation decreased for blood flux lower than baseline. This study's findings could be a basis for using LSCI in specific patient populations, such as burn care.

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.

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.

Gradual tapering TNF inhibitors versus conventional synthetic DMARDs after achieving controlled disease in patients with rheumatoid arthritis: first-year results of the randomised controlled TARA study.

OBJECTIVES: The aim of this study is to evaluate the effectiveness of two tapering strategies after achieving controlled disease in patients with rheumatoid arthritis (RA), during 1 year of follow-up. METHODS: In this multicentre single-blinded (research nurses) randomised controlled trial, patients with RA were included who achieved controlled disease, defined as a Disease Activity Score (DAS) ≤ 2.4 and a Swollen Joint Count (SJC) ≤ 1, treated with both a conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and a TNF inhibitor. Eligible patients were randomised into gradual tapering csDMARDs or TNF inhibitors. Medication was tapered if the RA was still under control, by cutting the dosage into half, a quarter and thereafter it was stopped. Primary outcome was proportion of patients with a disease flare, defined as DAS > 2.4 and/or SJC > 1. Secondary outcomes were DAS, European Quality of Life-5 Dimensions (EQ5D) and functional ability (Health Assessment Questionnaire Disability Index [HAQ-DI]) after 1 year and over time. RESULTS: A total of 189 patients were randomly assigned to tapering csDMARDs (n = 94) or tapering anti-TNF (n = 95). The cumulative flare rates in the csDMARD and anti-TNF tapering group were, respectively, 33 % (95% CI,24% to 43 %) and 43 % (95% CI, 33% to 53 % (p = 0.17). Mean DAS, HAQ-DI and EQ-5D did not differ between tapering groups after 1 year and over time. CONCLUSION: Up to 9 months, flare rates of tapering csDMARDs or TNF inhibitors were similar. After 1 year, a non-significant difference was found of 10 % favouring csDMARD tapering. Tapering TNF inhibitors was, therefore, not superior to tapering csDMARDs. From a societal perspective, it would be sensible to taper the TNF inhibitor first, because of possible cost reductions and less long-term side effects. TRIAL REGISTRATION NUMBER: NTR2754.