What benefit-risk trade-offs are acceptable to rheumatoid arthritis patients during treatment selection? Evidence from a multicountry choice experiment.

OBJECTIVE: Understanding preferences of patients with rheumatoid arthritis (RA) can facilitate tailored patient-centric care. This study elicited trade-offs that patients with RA were willing to make during treatment selection. METHODS: Patients with RA completed an online discrete choice experiment, consisting of a series of choices between hypothetical treatments. Treatment attributes were selected based on literature review and qualitative patient interviews. Eligible patients were ≥18 years old, diagnosed with RA, receiving systemic disease-modifying antirheumatic drug therapy, and residents of Europe or USA. Male patients were oversampled for subgroup analyses. Data were analysed using a correlated mixed logit model. RESULTS: Of 2090 participants, 42% were female; mean age was 45.2 years (range 18-83). Estimated effects were significant for all attributes (p<0.001) but varied between patients. Average relative attribute importance scores revealed different priorities (p<0.001) between males and females. While reducing pain and negative effect on semen parameters was most important to males, females were most concerned by risk of blood clots and serious infections. No single attribute explained treatment preferences by more than 30%. Preferences were also affected by patients' age: patients aged 18-44 years placed less importance on frequency and mode of treatment administration (p<0.05) than older age groups. Patients were willing to accept higher risk of serious infections and blood clots in exchange for improvements in pain, daily activities or administration convenience. However, acceptable trade-offs varied between patients (p<0.05). CONCLUSION: Treatment preferences of patients with RA were individual-specific, but driven by benefits and risks, with no single attribute dominating the decision-making.

What to Expect When Systemic Treatment in Juvenile Idiopathic Arthritis Is Withdrawn?

OBJECTIVE: The goal of juvenile idiopathic arthritis (JIA) treatment is to maintain clinical remission. It is also important to reduce drug exposure, whenever possible, in order to avoid or decrease potential side effects. We aimed to analyze remission survival after systemic treatment withdrawal and to determine which factors can influence it. METHODS: We conducted a multicenter, observational, longitudinal study. All patients included had a diagnosis of JIA. We analyzed remission survival using Kaplan-Meier curves according to the systemic treatment received (methotrexate [MTX] alone or in combination with biologic disease-modifying antirheumatic drugs [bDMARDs]) and JIA subgroups (oligoarticular and polyarticular course, juvenile spondyloarthritis, and systemic JIA). In addition, risk factors were examined using multivariate analysis. RESULTS: We included 404 patients with JIA; 370 of them (92%) had received systemic treatment at some point and half of them (185 patients) had withdrawn on at least 1 occasion. There were 110 patients who flared (59%) with a median time of 2.3 years. There were no differences in remission survival between JIA subcategories. Twenty-nine percent of patients with JIA who received MTX and bDMARDs, in which MTX alone was withdrawn, flared; median time to flare of 6.3 years. However, if only the bDMARD was withdrawn, flares occurred 57% of the time; median time to flare of 1.1 years. CONCLUSION: Flares are frequent when systemic treatment is withdrawn, and uveitis or joint injections could be related risk factors. In MTX and biologic-naïve patients, the frequency of flares occurred in more than half of patients, although they were less frequent when clinical remission lasted for > 1 year.

Salivary gland ultrasound in clinical practice: What is its real usefulness?

BACKGROUND: Salivary gland ultrasound (SGU) provides information about structural gland abnormalities that can be graded and used for primary Sjögren's syndrome (pSS) diagnosis. Its potential role as a prognostic marker for detecting patients at high risk of lymphoma and extra-glandular manifestations is still under evaluation. We aim to assess the usefulness of SGU for SS diagnosis in routine clinical practice and its relationship with extra-glandular involvement and lymphoma risk in pSS patients. METHODS: We designed a retrospective observational single-center study. Data was collected using the electronic health records of patients referred to an ultrasound outpatient clinic for evaluation over a 4-year period. Data extraction included demographics, comorbidities, clinical data, laboratory tests, SGU results, salivary gland (SG) biopsy, and scintigraphy results. Comparisons were made between patients with and without pathological SGU. The external criterion for comparison was the fulfillment of the 2016 ACR/EULAR pSS criteria. RESULTS: A total of 179 SGU assessments were included from this 4-year period. Twenty-four cases (13.4%) were pathological. The most frequently diagnosed conditions prior to SGU-detected pathologies were pSS (9.7%), rheumatoid arthritis (RA) (13.1%), and systemic lupus (4.6%). One hundred and two patients (57%) had no previous diagnosis (sicca syndrome work-up); of these, 47 patients (46.1%) were ANA positive and 25 (24.5%) anti-SSA positive. In this study, the sensitivity and specificity of SGU for SS diagnosis were 48% and 98% respectively, with a positive predictive value of 95%. There were statistically significant relationships between a pathological SGU and the presence of recurrent parotitis (p=.0083), positive anti-SSB antibodies (p=.0083), and a positive sialography (p=.0351). CONCLUSIONS: SGU shows high global specificity but low sensitivity for pSS diagnosis in routine care. Pathological SGU findings are associated with positive autoantibodies (ANA and anti-SSB) and recurrent parotitis.

What drives the decision to optimise biological treatment in children and youngsters with juvenile idiopathic arthritis? A discrete-choice experiment.

OBJECTIVE: To analyse factors involved in the decision to optimise biologics in juvenile idiopathic arthritis. METHODS: A "discrete-choice" methodology was used. In a nominal group meeting, factors which may influence physicians' decisions to optimise biological dose were identified, together with decision nodes. 1000Minds® was used to create multiple fictitious clinical scenarios based on the factors identified, and to deploy surveys that were sent to a panel of experts. These experts decided for each item which of two clinical scenarios prompted them to optimise the dose of biologic. A conjoint analysis was carried out, and the partial-value functions and the weights of relative importance calculated. RESULTS: In the nominal group, three decision nodes were identified: (1) time to decide; (2) to maintain/reduce or prolong interval; (3) what drug to reduce. The factors elicited were different for each node and included patient and drug attributes. The presence of macrophage activation syndrome (MAS), systemic involvement, or subclinical inflammation made the decision easier (highest weights). The presence of joints of difficult control and year of debut influenced the decision in some but not all, and in different directions. Immunogenicity, adherence, and concomitant treatments were also aspects taken into account. CONCLUSIONS: The decision to optimise the dose of biological therapy in children and youngster can be divided into several nodes, and the factors, both patient and therapy-related, leading to the decision can be detailed. These decisions taken by experts may be transported to practice, study designs, and guidelines.

The role of ultrasound and FDG-PET/CT to detect extracranial artery involvement in patients with suspected large vessel vasculitis.

OBJECTIVE: To assess the accuracy of ultrasound (US) versus fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) to identify extracranial involvement in large vessel vasculitis (LVV). METHODS: A retrospective observational study of patients with suspected LVV. All patients underwent US exam within 24 h per protocol. FDG-PET/CT was performed according to clinician criteria. The gold standard for LVV diagnosis was clinical confirmation after 6 months. RESULTS: Of the 113 patients included (74.3% female, mean age 74 years), 37 (32.7%) were diagnosed with LVV after 6 months. The sensitivity and specificity of US were 86.5% and 96.1%, respectively. Only 12 (42.9%) of 28 patients undergoing a FDG-PET/CT per clinician criteria showed positive findings. The sensitivity and specificity of FDG-PET/CT for LVV were 61.1% and 90%, respectively. Taking FDG-PET/CT as the reference, US showed extracranial inflammation in 10/12 (83.3%) and detected 2 (12.5%) additional cases of extracranial involvement with negative FDG-PET/CT. Conversely, FDG-PET/CT was positive in two patients with negative US (one isolated aortitis and one aortoiliac involvement). CONCLUSIONS: US and FDG-PET/CT are both valid tools to detect extracranial involvement. The presence of US extracranial artery inflammation is consistent with FDG-PET/CT examination, although a negative US scan does not rule out extracranial involvement.

Impact of cardiovascular risk on the diagnostic accuracy of the ultrasound Halo Score for giant cell arteritis.

OBJECTIVE: To evaluate the impact of cardiovascular risk (CVR) on the diagnostic accuracy of the ultrasonographic (US) Halo Score in patients with suspected giant cell arteritis (GCA). METHODS: Retrospective observational study of patients referred to our US fast track clinic with suspected GCA for a 2-year period. The intima-media thickness (IMT) of cranial and extra-cranial arteries and the Halo Score was determined to assess the extent of vascular inflammation. The European Society of Cardiology Guidelines on CV Disease Prevention were used to define different categories of CVR and patients were classified according to the Systemic Coronary Risk Evaluation (SCORE). The gold standard for GCA diagnosis was clinical confirmation after a 6-month follow-up. RESULTS: Of the 157 patients included, 47 (29.9%) had GCA after a 6-month follow-up. Extra-cranial artery IMT was significantly higher in patients with high/very high CVR than in those with low/moderate CVR, but only among patients without GCA. Non-GCA patients with high/very high CVR had also a significantly higher Halo Score in contrast with low/moderate CVR [9.38 (5.93) vs 6.16 (5.22); p = 0.007]. The area under the ROC curve of the Halo Score to identify GCA was 0.835 (95% CI 0.756-0.914), slightly greater in patients with low/moderate CVR (0.965 [95% CI 0.911-1]) versus patients with high/very high CVR (0.798 [95% CI 0.702-0.895]). A statistically weak positive correlation was found between the Halo Score and the SCORE (r 0.245; c = 0.002). CONCLUSIONS: Elevated CVR may influence the diagnostic accuracy of the US Halo Score for GCA. Thus, CVR should be taken into consideration in the US screening for GCA.

Inhibidores de receptores JAK quinasa e infección por virus varicela zoster en pacientes con artritis reumatoide. Revisión sistemática de la literatura / JAK Kinase Inhibitors and Varicella Zoster Virus Infection in Patients with Rheumatoid Arthritis. Systematic Review of the Literature

Objetivos: El objetivo de esta revisión sistemática es evaluar la infección por herpes zoster (HZ) publicada en los ensayos clínicos faseII y faseIII de pacientes con AR en tratamiento con inhibidores de JAK (iJAK). Material y métodos: Revisión sistemática de la literatura que evalúa la incidencia de HZ publicada en los ensayos clínicos de los distintos iJAK comercializados o en estudio. Resultados: Las tasas de HZ variaron entre el 1,51 y 20,22. Los resultados se expresaron principalmente en porcentaje de eventos. Los estudios más recientes categorizaron mejor la incidencia de HZ y su gravedad. Conclusión: Los iJAK se asocian a mayor riesgo de HZ. Aunque las tasas de HZ de los iJAK selectivos de JAK1 son menores, son necesarios más estudios que confirmen estos resultados.(AU)

Objectives: JAK kinase inhibitors (JAKi) are a new therapeutic option in the treatment of rheumatoid arthritis, but they are not without risks, especially the incidence of herpes zoster (HZ). Material and methods: Systematic literature review that evaluates the incidence of HZ published in the clinical trials of the different JAKis marketed or under study. Results: The HZ rates ranged between 1.51 and 20.22. The results were expressed mainly as a percentage of events. The most recent studies better categorized the incidence of HZ and its severity. Conclusion: JAKis are associated with an increased risk of HZ. Although the HZ rates of the selective JAK1 JAKis are lower, more studies are needed to confirm these results.(AU)

Ultrasound intima media thickness cut-off values for cranial and extracranial arteries in patients with suspected giant cell arteritis.

Objective: To determine the optimal ultrasound (US) cut-off values for cranial and extracranial arteries intima media thickness (IMT) to discriminate between patients with and without giant cell arteritis (GCA). Methods: Retrospective observational study including patients referred to an US fast-track clinic. All patients underwent bilateral US examination of the cranial and extracranial arteries including the IMT measurement. Clinical confirmation of GCA after 6 months was considered the gold standard for diagnosis. A receiver operating characteristic (ROC) analysis was performed to select the cut-off values on the basis of the best tradeoff values between sensitivity and specificity. Results: A total of 157 patients were included, 47 (29.9%) with clinical confirmation of GCA after 6 months. 41 (87.2%) of patients with GCA had positive US findings (61.7% had cranial and 44.7% extracranial involvement). The best threshold IMT values were 0.44 mm for the common temporal artery; 0.34 mm for the frontal branch; 0.36 mm for the parietal branch; 1.1 mm for the carotid artery and 1 mm for the subclavian and axillary arteries. The areas under the ROC curves were greater for axillary arteries 0.996 (95% CI 0.991-1), for parietal branch 0.991 (95% CI 0.980-1), for subclavian 0.990 (95% CI 0.979-1), for frontal branch 0.989 (95% CI 0.976-1), for common temporal artery 0.984 (95% CI 0.959-1) and for common carotid arteries 0.977 (95% CI 0.961-0.993). Conclusion: IMT cut-off values have been identified for each artery. These proposed IMT cut-off values may help to improve the diagnostic accuracy of US in clinical practice.

JAK kinase inhibitors and varicella zoster virus infection in patients with rheumatoid arthritis. Systematic review of the literature.

OBJECTIVES: JAK kinase inhibitors (JAKi) are a new therapeutic option in the treatment of rheumatoid arthritis, but they are not without risks, especially the incidence of herpes zoster (HZ). MATERIAL AND METHODS: Systematic literature review that evaluates the incidence of HZ published in the clinical trials of the different JAK is marketed or under study. RESULTS: The HZ rates ranged between 1.51 and 20.22. The results were expressed mainly as a percentage of events. The most recent studies better categorized the incidence of HZ and its severity. CONCLUSION: JAK is are associated with an increased risk of HZ. Although the HZ rates of the selective JAK1 JAK is are lower, more studies are needed to confirm these results.

Long-Term Retention Rate of Golimumab in Patients With Rheumatoid Arthritis, Psoriatic Arthritis, and Spondyloarthritis in a Real-Life Setting.

METHODS: We conducted a single-center, medical records review study of all patients with RA, PsA, and SpA on GLM treatment attending a large rheumatology department from 2010 to 2017. Times from start to end of GLM treatment were collected, as well as sociodemographic, clinical, and safety variables. Golimumab retention rate was estimated by the Kaplan-Meier method, and comparison across diseases was analyzed with the Mantel-Haenszel statistic (log-rank test). Cox proportional hazards regression models were used to identify factors associated with GLM discontinuation. RESULTS: In the study period, a total of 212 patients (61 RA, 48 PsA, 103 SpA) were prescribed GLM. Retention rates were 72% in the first year, 61% in the second, 56% in the third, and 38% at 5 years. Differences were statistically significant across diseases (median times to GLM discontinuation were 50.2, 46.0, and 38.7 months for RA, SpA, and PsA, respectively) and according to the number of previous biologic therapies (55.2 months in biologic-naive patients vs 14.0 months in patients with ≥2 previous biologics; p < 0.001). The use of concomitant conventional synthetic disease-modifying antirheumatic drugs was associated with a lower probability of discontinuation (hazards ratio [HR], 0.57; 95% confidence interval [CI], 0.33-0.97). Female sex (HR, 1.84; 95% CI, 1.07-3.17) and having used 2 biologics before GLM (HR, 2.99; 95% CI, 1.76-5.06) were associated with increased discontinuation rates. Twenty-three patients (10.9%) had at least 1 serious adverse event. CONCLUSIONS: In a real-life setting, GLM shows appropriate long-term safety-effectiveness ratio.

Radiosynovectomy in routine care: an old tool with modern applications.

OBJECTIVES: Radiosynovectomy can be an effective treatment for difficult-to-treat monoarthritis resistant to systemic and local standard therapy. The objective of our study was to determine predictors of good response to radiosynovectomy in routine care and give an overview of this underused technique. METHODS: Retrospective observational study of all the patients who underwent radiosynovectomy during a 6-year inclusion period. All the procedures were ultrasound guided and the radiopharmaceutical used was chosen according to joint size. The patient was considered to have an effective response to radiosynovectomy if the attending physician reported a positive outcome and there was no need to increase local and or systemic treatment due to arthritis in the affected joint during the next 12 months following the procedure. RESULTS: We included 67 patients who underwent radiosynovectomy in the knee (73.1%), wrist (16.4%), and elbow (10.5%). Overall, 44 (65.7%) procedures were considered effective. In the multivariate analysis, infiltration of wrists (odds ratio = 0.192; confidence interval = 0.046-0.79) and pigmented villonodular synovitis (odds ratio = 0.13; confidence interval = 0.021-0.82) were independently associated with a noneffective response. No patients experienced complications associated with radiosynovectomy during follow-up. CONCLUSION: Infiltrations of wrists with joint damage seem less likely to have a response to radiosynovectomy. In pigmented villonodular synovitis, radiosynovectomy as an adjuvant therapy for relapse might not be effective when performed more than 6 months after surgery. Overall, radiosynovectomy is an effective and safe treatment for persistent monoarthritis.

Ultrasound in clinically suspect arthralgia: the role of power Doppler to predict rheumatoid arthritis development.

OBJECTIVE: To determine the usefulness of power Doppler (PD) ultrasound (US) to predict rheumatoid arthritis (RA) development in patients with clinically suspect arthralgia (CSA). METHODS: Retrospective analysis of a US unit cohort over a 1-year period. Patients with CSA and no previous diagnosis of inflammatory arthritis (IA) were included for analysis. All underwent bilateral US examination of the hands and/or feet according to the EULAR guidelines. Active US inflammation was defined as PD synovitis and/or tenosynovitis ≥1 at any location. RA diagnosis according to clinician criteria 6 months after the US examination was checked. Univariate and multivariate logistic regression models were employed to investigate possible predictive factors of RA development. RESULTS: A total of 110 CSA patients (80 females, mean age 53.6 years) were included for analysis. After 6 months of follow-up, 14 (12.7%) developed RA and 34 (30.9%) IA. US active inflammation was present in 38 (34.5%) patients (28.2% showed PD synovitis and 18.2% PD tenosynovitis). Multivariate analysis showed that ACPA (OR 1.0003; 95% CI 1.002-1.006) and ESR (OR 1.054; 95% CI 1.016-1.094) were significantly associated with the detection of US active inflammation at baseline. Only PD tenosynovitis was found to be an independent predictive factor of an evolution towards RA (OR 6.982; 95% CI 1.106-44.057) and IA (OR 5.360; 95% CI 1.012-28.390). CONCLUSION: US is able to detect features of subclinical inflammation in CSA patients, especially in those with higher ESR and ACPA values. Only PD tenosynovitis at baseline US assessment was found to be an independent predictor of RA and IA development in CSA patients.

Persistence and adherence to biologic therapies in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease that often requires biological therapy to control its activity. Medication persistence and adherence are important aspects on which we have scarce information. We performed a longitudinal, retrospective, and observational study based on data from the daily clinical management of JIA patients. We recorded clinical remission at 6 and 12 months. Persistence of biological therapy was evaluated using Kaplan-Meier curves, and adherence was assessed using the medication possession ratio (MPR). We included 68 patients who received biological therapy. Of these, 11 (16.2%) and 5 (7.4%) required a second and third drug, respectively. The persistence rate for biological therapy at 5 years was 64%, with no differences between the first and second lines. Adherence was high during the first year of treatment (MPR80: 96.3%) and also in the second and third years (MPR80: 85.2% and 91.8%, respectively). Persistence and adherence to biological therapy were remarkably high in our JIA cohort. Adherence to biological treatments could be related to a higher probability of fulfilling the Wallace remission criteria at 6 months, although this was not confirmed at 12 months.

Subclavian artery involvement in patients with giant cell arteritis: do we need a modified Halo Score?

OBJECTIVE: To assess whether adding the subclavian artery examination into the ultrasound (US) Southend Halo Score, as proposed in the modified Halo Score, improves the diagnostic accuracy of giant cell arteritis (GCA) and its relationship with systemic inflammation. METHODS: Retrospective observational study of patients referred to a GCA fast track pathway (FTP) over a 1-year period. Patients underwent US exam of temporal and large vessel (LV) (carotid, subclavian, and axillary) arteries. The extent of inflammation was measured by the halo count, the Southend Halo Score, and the modified Halo Score. The gold standard for GCA diagnosis was clinical confirmation after 6-month follow-up. RESULTS: Sixty-four patients were evaluated in the FTP, 17 (26.5%) had GCA. Subclavian artery involvement was present only in patients with GCA (29.4% versus 0%, p < 0.001). Overall, the three scores showed excellent diagnostic accuracy for GCA (ROC AUC 0.906, 0.930, and 0.928, respectively) and moderate correlations with acute phase reactants (0.35-0.51, p < 0.01). Only the modified Halo Score correlated with markers of inflammation in patients with LV involvement. CONCLUSIONS: The inclusion of subclavian artery examination in the modified Halo Score does not improve the diagnostic accuracy of GCA. Nevertheless, it correlates better with markers of systemic inflammation in LV-GCA. Key Points • Adding the subclavian artery examination into the Southend Halo Score, as proposed in the modified Halo Score, does not improve the diagnostic accuracy of GCA. • However, the extent of vascular inflammation as quantified by the modified Halo Score correlates better with markers of systemic inflammation in the large vessel (LV) GCA subgroup of patients. • Although the diagnostic value of adding subclavian arteries to the current recommended US examination of GCA is limited, it may have a role in monitoring disease activity as it correlates with the general burden of inflammation in LV GCA. These findings need to be confirmed in additional populations and larger prospective studies.