Search

The aim of this study was to analyze the therapeutic results of rheumatoid arthritis (RA) therapy with different biologic disease-modifying antirheumatic drugs (bDMARDs) and the first Janus-activated kinase (JAK) inhibitor in real-life clinical settings. This is a prospective, observational, longitudinal study at the largest rheumatology clinic in Bulgaria conducted during the period 2012-2020. One hundred seventy-four patients were followed up for a period of one year. Patients naïve to biological therapy were consecutively assigned on the available at the time bDMARDs (infliximab, etanercept, adalimumab, rituximab, golimumab, cetrolizumab, tocilizumab) or tofacitinib. We evaluated the disease activity score (DAS28-CRP), Health assessment questionnaires (HAQ) and short form 36 (SF-36) were applied at the initiation of biological therapy, after 6, and 12 months of follow-up. We analyze the changes in the two major subgroups of SF36-physical (MCS) and mental health (PCS). The age and gender distribution were similar between the groups on bDMARDs and tsDMARD. All observed indicators for disease control and QoL improve after the initiation of the biological or JAK inhibitor therapy. We also analyze the effect of therapies on DAS28-CRP, HAQ, SF-36 (PCS, MCS). Dispersion analysis for the effect of therapy measured through DAS28 between 1st and 3rd measurement shows a statically significant difference in between the average effect of therapies (p = 0.005). According to the average change in DAS28 between the first and third measurement the most effective is the golimumab (Median difference = 2.745), followed by rituximab (median = 2.305) and etanercept (median = 2.070). According to the average change in HAQ between first and third the most effective is tofacitinib (median 0.563), followed rituximab and infliximab (median 0.500 for both). Less effective in term of HAQ changes between the first and third measurement appears to be etanercept (median difference 0.250). All differences are statistically significant (p 0.05). Regarding the changes in the QoL measured with SF-36 MCS and PCS there is no statistically significant differences in the average effect of different therapeutic agents. Tofacitinib is non-inferior in comparison to bDMARDs and improve both-disease activity and QoL in patients with RA.

Nanomedicine (NM) is the medical use of nanotechnology (NT). NT is the study and control of nanoscale structures (between approximately 1 and 100 nm). Nanomaterials are created by manipulating atoms and molecules at the nanoscale, resulting in novel physical and chemical properties. With its targeted tissue delivery capabilities, NT has enabled molecular modulation of the immune response and underlying inflammatory responses in individuals with rheumatic diseases (RD). NM has enabled targeted drug delivery, reduced adverse effects on non-target organs, raised drug concentration in synovial tissue, and slowed the progression of immune-mediated RD such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Thus, NM has evolved in rheumatology prevention, diagnosis, and therapy. Animal models have proven superior outcomes to conventional techniques of treating specific illnesses. Nanodiamond (ND) immunomodulatory applications have been proposed as an alternative to traditional nanoparticles in the diagnosis and treatment of RA due to their small size and ability to be removed from the body without causing harm to the patient's organs, such as the liver. However, human clinical NM needs more research. We conducted a literature review to assess the present role of NM in clinical rheumatology, describing its current and future applications in the diagnosis and treatment of rheumatic diseases.

Factors influencing prognosis after administration of the last biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) to patients with difficult-to-treat rheumatoid arthritis (D2T_RA) were evaluated in a clinical setting. RA patients who met the EULAR definition of D2T_RA were recruited. These patients were grouped according to success/failure. Success was defined as sustained within light disease activity or discontinued after clinical remission, and all of the following were met, including glucocorticoid (GCS) 7.5 mg/day, no rapid radiographic progression, and improved quality of life from the beginning of the b/tsDMARD (baseline). Failure was defined as any other condition from success. The primary endpoint of the study was success or failure at 12 months after baseline. Factors influencing success/failure were statistically evaluated. A total of 71 D2T_RA patients were selected, 22 were in the success group and 49 in the failure group. For patients taking GCS and methotrexate (MTX) ≤ 8.6 mg/week, only one was included in the success group and the other 24 were included in the failure group (p 0.001). Of the 18 patients without GCS and with MTX ≥ 8.7 mg, 12 patients whose 28-joint disease activity score ≤ 1.90 at 3 months or ≤ 2.54 at 6 months were in the success group (p 0.01). D2T_RA patients with GCS or MTX ≤ 8.6 mg at baseline are considered to be at high risk of repeat D2T_RA. Patients with no GCS and MTX ≥ 8.7 mg are more likely to withdraw from D2T_RA if their disease activity is tightly controlled.

International audience; To develop and validate a questionnaire assessing patient knowledge in rheumatoid arthritis (RA). Knowledge considered essential for patients with RA was identified through a series of Delphi rounds among rheumatologists, health professionals (HPs), patients, and then reformulated to construct the knowledge questionnaire. Cross-sectional multicenter validation was performed in 12 rheumatology departments to assess internal validity (Kuder\textendash Richardson coefficient), external validity, acceptability, reproducibility (Lin's concordance correlation coefficient) and sensitivity to change (difference in total score before and after patient education sessions). Associations between patient variables and knowledge levels were evaluated. RAKE (RA Knowledge questionnairE) is a self-administered 45-item questionnaire scored 0\textendash 100, with a 32-item short-form survey assessing knowledge of disease, comorbidity, pharmacological treatments, non-pharmacological treatments, self-care and adaptative skills. Of 130 patients included in the validation study, 108 were women. Acceptability was good with\

The study aimed to compare treatment retention for first-line TNF inhibitor (TNFi) in the ATTRA registry patients receiving either combination with conventional synthetic DMARDs or TNFi as monotherapy. A retrospective multicenter study analyzed data of all adult patients with rheumatoid arthritis (n = 3032) starting TNF inhibitor as the first-line biological therapy in combination with csDMARDs or in monotherapy from January 1st 2012 to December 31st 2020. Kaplan–Meier method was employed to calculate drug retentions. Survival curves of treatment retentions were compared through Log-rank test between the studied subgroups. The hazard ratio for drug discontinuation was assessed through univariate cox regression models. In patients who started the first line TNFi therapy, the median treatment retention was 47.7 (42.2; 53.1) months for combination therapy and 22.7 (14.9; 30.6) months for TNFi monotherapy (p p = 0.003). Use of csDMARDs co-medication was associated with significantly better first TNFi drug survival compared to monotherapy. The combination of TNFi with MTX is more effective than the combination with leflunomide, which did not demonstrate a significant effect.

Rheumatoid factor (RF) binds to the fragment crystallizable (Fc) portion of immunoglobulin. It could bind to the Fc portion of anti-TNF inhibitors (TNFi) and attenuate the clinical efficacy. We tried to determine whether the therapeutic efficacy of TNFi with Fc might be lower than that of TNFi without Fc in rheumatoid arthritis (RA) patients with high titres of RF. The Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational multi-center registry of patients with RA in the Kansai district of Japan. RA patients treated with TNFi were included and divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, and etanercept) and TNFi without Fc (certolizumab pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was compared by Mann-Whitney U test between TNFi with and without Fc in each RF titre group. Multiple linear regression analysis was used to analyze the effect of TNFi without Fc for the change of DAS28-ESR adjusted after potential confounders. A total of 705 RA patients were classified into four groups (RF

Rheumatoid arthritis is a severe chronic autoimmune disorder that results from pathological activation of immune cells and altered cytokine/chemokine network. The aim of our study was to evaluate concentrations of chosen cytokines and chemokines in blood sera and synovial fluid samples isolated from low disease activity rheumatoid arthritis (RA) patients and osteoarthritis (OA) sufferers. Blood sera and synovial fluid samples have been obtained from 24 OA and 14 RA patients. Cytokines/chemokines levels have been determined using a Milliplex®Map 38-plex human cytokine/chemokine magnetic bead-based panel (Merck Millipore, Germany) and Luminex®MAGPIX®platform (Luminex USA). Low disease activity RA patients showed altered concentration of numerous cytokine/chemokine when compared to OA controls—they were characterized by, inter alia, increased: eotaxin/CCL11 (p = 0.037), GRO/CXCL1 (p = 0.037), IL-2 (p = 0.013), IL-4 (p = 0.017), IL-7 (p = 0.003), IL-8 (p = 0.0007) and GM-CSF (p = 0.037) serum levels, whilst MDC/CCL22 concentration was decreased in this group (p = 0.034). Eotaxin/CCL11 (p = 0.001), GRO/CXCL1 (p = 0.041), IL-10 (p = 0.003), GM-CSF (p = 0.01), IL-1RA (p = 0.0005) and VEGF (p = 0.01) concentrations in synovial fluid of RA females were also increased. Even with low disease activity score, RA patients exhibited increased concentrations of cytokines with pro- and anti-inflammatory activities, as well as numerous chemokines, growth factors and regulators of angiogenesis. Surprisingly, RA subjects also shown decreased concentration of CCL22 chemokine. The attempt to restore cytokine balance and tolerogenic environment is ineffective in RA sufferers even with good disease management. Distinguished factors could serve as possible indicators of disease progression even in low disease activity patients.

Rheumatoid arthritis (RA) is an autoimmune disorder of unknown etiology with aberrant immunological responses leading to inflammation, swelling and pain of the joints. CD8

The Handscan is a novel objective optical imaging device for disease follow-up and management in rheumatoid arthritis patients. We aim to examine the association between the baseline outcomes of the Handscan, disease activity levels and joint swelling. The Handscan measures differences in laser light absorption between joints of fingers and wrists and adjacent reference tissue, indicating the presence or absence of inflammation. The device gives an optical spectral transmission (OST) index per joint. The average of these indices is represented in the total optical score (TOS). Associations between TOS and DAS28 at subject level and OST and swelling at joint level were examined. 484 RA patients were included. Compared to patients with high disease activity (defined by DAS28), TOS was significantly lower in patients with moderate (estimated coefficient B: - 7.09, P < 0.001), low disease activity (B: - 6.99, P < 0.001) and patients in remission (B: - 7.72, P < 0.001) but could not distinguish between the latter three disease states. TOS was significantly lower in females (B: - 3.2, P < 0.001). OST was significantly higher in swollen than non-swollen joints (B: 0.28, P < 0.001). TOS was significantly higher in patients with high disease activity than in those in remission or with low and moderate disease activity. The difference in TOS between males and females should be accounted for in the interpretation of this outcome. The OST at joint level discriminates swollen from non-swollen joints and could be a more promising tool than the overall optical activity reflected in TOS.

The study proposes a novel machine learning (ML) paradigm for cardiovascular disease (CVD) detection in individuals at medium to high cardiovascular risk using data from a Greek cohort of 542 individuals with rheumatoid arthritis, or diabetes mellitus, and/or arterial hypertension, using conventional or office-based, laboratory-based blood biomarkers and carotid/femoral ultrasound image-based phenotypes. Two kinds of data (CVD risk factors and presence of CVD-defined as stroke, or myocardial infarction, or coronary artery syndrome, or peripheral artery disease, or coronary heart disease) as ground truth, were collected at two-time points: (i) at visit 1 and (ii) at visit 2 after 3 years. The CVD risk factors were divided into three clusters (conventional or office-based, laboratory-based blood biomarkers, carotid ultrasound image-based phenotypes) to study their effect on the ML classifiers. Three kinds of ML classifiers (Random Forest, Support Vector Machine, and Linear Discriminant Analysis) were applied in a two-fold cross-validation framework using the data augmented by synthetic minority over-sampling technique (SMOTE) strategy. The performance of the ML classifiers was recorded. In this cohort with overall 46 CVD risk factors (covariates) implemented in an online cardiovascular framework, that requires calculation time less than 1 s per patient, a mean accuracy and area-under-the-curve (AUC) of 98.40% and 0.98 (p 0.0001) for CVD presence detection at visit 1, and 98.39% and 0.98 (p 0.0001) at visit 2, respectively. The performance of the cardiovascular framework was significantly better than the classical CVD risk score. The ML paradigm proved to be powerful for CVD prediction in individuals at medium to high cardiovascular risk.

Methotrexate (MTX) is recommended as a first-line treatment for rheumatoid arthritis (RA). There are no strict guidelines regarding monitoring for liver damage in RA patients. This study aimed to evaluate noninvasive diagnostic procedures in assessing liver fibrosis in RA patients. Ninety-six RA patients were recruited for this study. The procollagen III N-terminal peptide (PIIINP) serum level was measured in all patients. The Enhanced Liver Fibrosis score (ELF-1) was calculated for 82 patients. Transient elastography (TE) was performed in 91 patients, those examined were divided into two groups: a study and control group, comprising patients with and without risk factors for liver fibrosis, respectively. The TE result correlated only with the body mass index—BMI (p p = 0.33). The TE result was significantly higher in those with risk factors for liver fibrosis than in those without risk factors (TE result > = 7.1 kPa 28/42 vs 13/41, HR = 2.103, Mann–Whitney U test, approximately 0.02). There was a positive correlation between the PIIINP level and body weight (p = 0.028), cumulative MTX dose (p = 0.007), RA activity (p = 0.028) and diabetes mellitus (DM) (p = 0.001). There was a positive correlation between the ELF-1 score and age (p p = 0.007) and RA activity (p

To enable patients with rheumatoid arthritis (RA) and their healthcare professionals to choose the optimal treatment, it is crucial to accurately assess the current state of inflammatory activity. The objectives of this study were to (1) investigate the perspective of RA patients on their insight into the current status of their disease, and to (2) investigate the patients’ perspective on the possible added value of a monitoring device based on optical spectral transmission—called the HandScan—that measures the location and severity of joint inflammation. A survey was distributed online among patients with RA in the Netherlands. Four-hundred and eight patients with RA completed the survey. Of these, 298 (73%) felt they have sufficient insight into their current disease status. Most respondents perceived either a large (n = 242; 59%) or small (n = 148; 36%) added value of the HandScan in their monitoring process, mostly because the device provides additional knowledge on the presence of inflammation. This perceived added value was higher for respondents experienced with the device (n = 46; p = .04). Respondents preferred monitoring with the device on every (n = 192; 47%) or most (n = 171; 42%) visits to the outpatient clinic, or even more often than on every visit (n = 17; 4%). Monitoring RA using an optical spectral transmission device is seen by patients as a possibly valuable addition to the monitoring process of inflammatory activity during visits to an outpatient clinic. Their main reason was that the device can increase insight into their current disease status. More insight may support patients in discussing treatment options with their rheumatologist.

Lack of sufficient head-to-head trials comparing biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA), makes the choice of the first bDMARD a matter of rheumatologist's preference. Longer drug survival on the first bDMARD usually correlates with early remission. We aimed to identify factors associated with longer drug survival. We conducted a population-based retrospective longitudinal cohort study. We identified RA patients using the relevant International Classification of Disease 9th codes. "True" RA patients were defined as patients fulfilling, additionally, at least one of the following: receiving conventional DMARDs (cDMARDs), being positive for rheumatoid factor or anti-cyclic citrullinated peptide, or being diagnosed by a rheumatologist. We compared drug survival times and identified factors associated with longer drug survival. We identified 4268 true RA patients between the years of 2000-2017. 820 patients (19.2%) received at least one bDMARD. The most commonly prescribed bDMARDs were etanercept (352, 42.9%), adalimumab (143, 17.4%), infliximab (142, 17.3%) and tocilizumab (58, 7.1%). Infliximab was associated with the longest drug survival (47.1 months ± 46.3) while golimumab was associated with the shortest drug survival (14.9 months ± 15.1). Male gender [hazard ratio (HR) = 0.76, 95% confidence interval (CI), 0.63-0.86, p = 0.001], concurrent conventional DMARDs use (HR = 0.79, 95% CI 0.68 - 0.98, p = .031) and initiating bDMARD therapy in earlier calendric years (HR = 1.12, 95% CI 1.10 -1.18, p = 0.0001) were associated with longer drug survival. Male gender, concomitant cDMARDs and initiating biologic therapy at earlier calendric years are associated with longer drug survival.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were launched in December 2020. Vaccination of patients with rheumatic diseases is recommended, as they are considered at higher risk of severe COVID-19 than the general population. Patients with rheumatic disease have largely been excluded from vaccine phase 3 trials. This study explores the safety and reactogenicity of BNT162b2 among patients with rheumatic diseases. Patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), median age 58.8 years, 285 subjects in total, were vaccinated twice with the BNT162b2 (Pfizer/BioNTech). Questionnaires on reactogenicity matching the original phase 3 study were answered seven days after completed vaccination. The majority of SLE and RA patients experienced either local (78.0%) or systemic reactions (80.1%). Only 1.8% experienced a grade-4 reaction. Compared to the original study, we found more frequent fatigue [Odds ratio (OR) 2.2 (1.7-2.8)], headache [OR 1.7 (1.3-2.2)], muscle pain [OR 1.8 (1.4-2.3)], and joint pain [OR 2.3 (1.7-3.0)] in patients. In contrast, the use of antipyretics was less frequent [OR 0.5 (0.3-0.6)]. Patients with SLE and RA experience reactogenicity to the Pfizer-BioNTech BNT162b2 COVID-19 vaccine. Reactogenicity was more frequent in patients, however, not more severe compared with healthy controls.

Rheumatoid arthritis (RA) was significantly associated with increased overall risk of periodontitis, both chronic, inflammatory pathologies leading to connective tissue breakdown and bone destruction. To identify clinical and/or serological variables routinely evaluated during follow-up of people with RA which are associated with the severity of their periodontal disease. An observational, cross-sectional study was carried out, which included RA patients according to ACR/EULAR 2010 criteria having chronic periodontal disease. RA clinical parameters (disease duration, erythrocyte sedimentation rate, serum C-reactive protein, disease activity (DAS28) and rheumatoid factor, presence of bone erosions and rheumatic nodules) and also corticosteroid therapy were considered. Periodontitis was evaluated according to the American Academy of Periodontology (1999) and chronic periodontitis was assessed by full mouth periapical radiographic examination, periodontal probing depth, clinical attachment level and bleeding index. A total of 110 subjects with RA and chronic periodontitis were included. The female/male relation was 5.1, and no significant differences between genres were found in rheumatic or oral variables. RA patients with longer disease duration, higher disease activity and with rheumatic nodules had significantly greater periodontitis severity. Multivariate analysis confirmed that severe periodontitis was associated with DAS283 4.1 (OR 51.4, CI 95% 9.4–281.5) and the presence of rheumatic nodules (OR 6.4, CI 95% 1.3–31.6). Disease activity and rheumatic nodules were strongly associated with severe periodontitis. Based on these findings it would be desirable to include interdisciplinary management at an early stage of RA to ensure comprehensive treatment of both pathologies

This study aimed to examine the progression of large joint involvement from early to established RA in terms of range of movement (ROM) and time to joint surgery, according to the presence of rheumatoid factor (RF). We used a historical longitudinal cohort of early RA patients. Patients were deemed RF negative if all repeated assessments were negative. The rate of progression from normal to any loss of range of movement (ROM) from years 3 to 14 were modelled using generalized estimating equations, for elbows, wrists, hips, knees and ankle, adjusting for confounders. Time to joint surgery was analysed using multivariable Cox models. A total of 1458 patients were included (66% female, mean age 55 years) and 74% were RF-positive. The prevalence of any loss of ROM, from year 3 through to 14 was highest in the wrist followed by ankle, knee, elbow and hip. Odds of loss of ROM increased over time in all joint regions assessed, at around 7–13% per year from year 3 to 14. Time to surgery was similar according to RF-status for the wrist and ankle, but RF-positive cases had a lower hazard of surgery at the elbow (HR 0.37, 0.15–0.90), hip (HR 0.69, 0.48–0.99) and after 10 years at the knee (HR 0.41, 0.25–0.68). Large joints become progressively involved in RA, most frequently affecting the wrist followed by ankle, which is overlooked in composite disease activity indices. RF-negative and positive cases progressed similarly. Treat-to-target approaches should be followed irrespective of RF status.

Neutropenia is a common adverse event of tocilizumab (TCZ) in rheumatoid arthritis (RA) patients; however, the association between the decrease in neutrophil counts and the TCZ clinical efficacy remains inconclusive. This study aimed to examine whether TCZ-induced neutrophil decrease at 1 month predicts clinical remission within 1 year. We reviewed medical records of RA patients initiating TCZ between May 2011 and September 2019 in our hospital. The Clinical Disease Activity Index (CDAI) was evaluated at baseline (before initiating TCZ) and 1, 3, 6, and 12 months after administration. Clinical remission was defined when CDAI decreased ≤ 2.8. The ratio of neutrophil counts 1 month after initiating TCZ to those at baseline (neutrophil ratio) was also calculated. Among 255 TCZ-treated patients, 169 with valid CDAI and neutrophil counts were enrolled (with median age of 60 years and 79% females). Rheumatoid factor and anti-cyclic citrullinated peptide antibody were positive in 75% and 83%, respectively, and 56% of the patients had concomitant methotrexate (median dose: 8 mg/week). Multivariate logistic regression analysis suggested baseline CDAI (odds ratio (OR) 0.96, p = 0.045), concomitant PSL (OR 0.42, p = 0.030), and the neutrophil ratio (OR 0.19, p = 0.011) as predictors of CDAI remission. Neutrophil ratio ≤ 0.8 was associated with achieving remission (Fisher's exact test, p = 0.02) with no apparent increase of severe infection. More than 20% reduction of neutrophil count 1 month after initiating TCZ predicts clinical remission within 1 year at an early treatment phase.

The aim of this study was to investigate the effects of lockdown on the mental health (anxiety and depression) and quality of life (QOL) of people with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in the context of the COVID-19 pandemic and public health measures instituted at a national level by the New Zealand Government. The present cohort was 104 individuals with RA (73.1%) and AS (26.9%) who had previously completed surveys for the Patient Opinion Real-Time Anonymous Liaison (PORTAL) project in 2018. Participants completed an online survey between July and September 2020 assessing their experiences over the first national COVID-19 lockdown in New Zealand (March-May, 2020). Fear of SARS-CoV-2 infection, baseline anxiety, and being younger in age were all predictors of participants' current anxiety levels. Current QOL scores were significantly lower than prior to lockdown and were predicted by baseline QOL and current depression. No variables predicted current depression other than baseline levels. The COVID-19 pandemic appears to have had an impact on QOL and anxiety levels, but not depression for people with RA and AS in New Zealand. These novel findings imply that appropriate screening of mental health issues should be included in planning within the ongoing COVID-19 pandemic and for future pandemics to optimise the wellbeing of people with RA and AS.

Medication compliance is critical to achieve therapeutic efficacy in patients with rheumatoid arthritis; however, among other factors, low patient-health literacy plays a negative role. Therefore, the development and validation of audiovisual educational material with the participation of health specialists and patients could lead to an improved level of compliance with treatment, while favoring its acceptance. To design and validate audiovisual educational material generated by a multidisciplinary and participative group of patients and health specialists. This study was carried out using a sequential methodology, including qualitative and quantitative techniques: (1) a non-participative observational study with patients and a non-systematic literature search were performed to identify conceptual topics. (2) Pilot videos were qualitatively assessed by patients and health specialists (focus groups and expert committees). (3) Improved versions of seven videos were quantitatively evaluated by patients and specialists following qualitative criteria of attraction, understanding, involvement, acceptance and induction of action. 74 patients with RA, 10 rheumatologists, 4 pharmacists and 2 medical anthropologists participated in the different phases of validation. A total of seven videos lasting 3 min each were generated, incorporating the most relevant suggestions by patients and healthcare professionals. The final version of the videos led to a mean compliance of 96.04 ± 5.2%, according to a representative group of patients and a mean 89.6 ± 9.4%, according to health professionals. With the participation of both patients and health specialists, seven audiovisual educational video recordings were developed and validated, reaching high levels of compliance in accordance with international criteria.

This study used data from a large-scale multicenter medical information database in Japan to estimate the incidence rate of herpes zoster (HZ) and to examine the relationship between hypertension, dyslipidemia, and diabetes mellitus (DM), and the risk of HZ among patients with rheumatoid arthritis (RA). The research dataset consisted of 221,196 records of potential target patients with RA extracted between April 1, 2008 and August 31, 2017 from the Medical Data Vision database. To assess the association between hypertension, dyslipidemia, and DM and the risk of HZ, a case–control study was set up. Records of 101,498 study subjects met the inclusion criteria. During the observation period, 2566 patients developed HZ and the overall incidence rate was 5.2 (95% confidence interval: 5.0–5.4 per 1000 patient-years). Hypertension, dyslipidemia, and DM were significantly associated with an increased risk of HZ after adjustment for sex, age, hospital size, and use of anti-rheumatic drugs. When mutual adjustment was made for hypertension, dyslipidemia, and DM, the positive associations between hypertension and dyslipidemia and the risk of HZ remained significant; however, the positive association with DM completely disappeared. RA patients with hypertension or dyslipidemia may be at higher risk of HZ. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04889-1.

Rheumatoid arthritis (RA), a long-term auto-immune condition is a challenging condition for patients to manage. Goals of treatment include reducing pain, decreasing inflammation, and improving an individual’s overall function. Increasingly technology is being utilised to support patients to self-manage their condition. The aim of this systematic narrative review was to synthesise and critically appraise published evidence concerning the effectiveness of tele-health interventions to support self-management in RA. Bibliographic databases searched from 2014 to March 2020 included MedLINE, Embase, Cochrane Library. Search strategy combined the following concepts: (1) rheumatoid arthritis, (2) tele-health interventions, and (3) self-management. Only randomised controlled trials (RCTs) involving adults with RA were included. Titles, abstracts, full-text articles were screened, any discrepancies were checked by a second reviewer. Risk of bias was assessed using Cochrane risk of bias tool and data were extracted utilising the Cochrane data collection form for RCT interventions along with the TiDier checklist. Due to high heterogeneity, results were not meta-analysed and instead data were synthesised narratively. The search identified 98 articles, seven were included. The completed RCTs varied in the nature of the interventions, duration/severity of RA, outcomes measured and effectiveness of the interventions. The completed RCTs included a total of 791 participants Disease duration was largely between 4 and 10 years and disease severity on average was moderate. There was extensive variation in intervention components, theories underpinning theories and outcomes measured. Five RCTs reported a positive effect on factors such as disease activity, medication adherence, physical activity and self-efficacy levels. This study suggests that tele-health interventions that are well-designed, tailored and multi-faceted can help to achieve positive self-management outcomes in RA. None of the studies showed evidence of harm. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04907-2.

To design and develop a smartphone application for a structured hand exercise programme for patients with rheumatoid arthritis (RA) in Turkey and to test its usability. We followed a two-stage process: (1) Design and Development and (2) Usability testing. In stage 1, we used a qualitative user-centered design approach. We conducted a focus group (8 therapists and people with RA) to discuss the content, features and design to produce a prototype of the application. In a second focus group session, the participants tested the prototype, provided feedback and further revisions were made. In stage 2, 17 participants with RA used the app for 4 to 6 weeks. The System Usability Scale and the adapted Usability, Satisfaction and Ease to Use Questionnaires were used to measure usability, ease of use. Semi-structured interviews were conducted to explore user experiences with the application with 17 participants. In stage 1, the following themes were identified from the focus groups (a) login techniques (b) self-monitoring (c) exercises, (d) exercise diary, (e) information, (f) behavioral change and encouragement (g) exercise adherence. In stage 2, 3 themes were determined from interviews: (a) learning and accuracy, (b) ease of use, (c) motivation and adherence. USE and SUS scores indicated that users reported a high level of usability, satisfaction and ease of use. A mobile app for hand exercise for people with RA was developed using a mixed-method and iterative design. Participants perceived the mobile app as easy to use with high levels of satisfaction.

The human microbiome has attracted attention for its potential utility in precision medicine. Increasingly, more researchers are recognizing changes in intestinal microbiome can upset the balance between pro- and anti-inflammatory factors of host immune system, potentially contributing to arthritis immunopathogenesis. Patients who develop rheumatoid arthritis from undifferentiated arthritis can face multiple irreversible joint lesions and even deformities. Strategies for identifying undifferentiated arthritis patients who have a tendency to develop rheumatoid arthritis and interventions to prevent rheumatoid arthritis development are urgently needed. Intestinal microbiome dysbiosis and shifts in the miRNA profile affect undifferentiated arthritis progression, and may play an important role in rheumatoid arthritis pathophysiologic process via stimulating inflammatory cytokines and disturbing host and microbial metabolic functions. However, a causal relationship between microbiome–miRNA interactions and rheumatoid arthritis development from undifferentiated arthritis has not been uncovered yet. Changes in the intestinal microbiome and miRNA profiles of undifferentiated arthritis patients with different disease outcomes should be studied together to uncover the role of the intestinal microbiome in rheumatoid arthritis development and to identify potential prognostic indicators of rheumatoid arthritis in undifferentiated arthritis patients. Herein, we discuss the possibility of microbiome–miRNA interactions contributing to rheumatoid arthritis development and describe the gaps in knowledge regarding their influence on undifferentiated arthritis prognosis that should be addressed by future studies.

Rheumatoid arthritis (RA) patients often report lacking information on medication side effects. The aims of this study were to observe how rheumatology healthcare providers deliver medication information and to determine in which specific domains information is missing. First, 12 single-blinded structured observations were performed during regular RA patient consultations. The observers noted whether and how medication and medication side effects were discussed. Second, 100 RA patients were asked to fill out an adaptation of the Satisfaction with Information about Medicines Scale (SIMS). Medication was discussed during all observed consultations. With new medication, its purpose and mode of action were explained in all cases, but possible side effects in only 33%. Overall, medication side effects were discussed in 58% of consultations. Most information delivery was verbal (92%). Response rate to the questionnaire was 61%. Overall satisfaction with medication education was mean 7.3 (± 1.9) (NRS 0–10) with a comparable high SIMS total satisfaction sum score of mean 12.3 (± 4.4). At subscale score levels, 89% were satisfied with the amount of information on the action and usage of medication, but only 47% with the information on the potential problems of medication. RA patients express overall high satisfaction with their medication education but there is still an unmet need for information on potential risks and side effects. Using the SIMS questionnaire in daily clinical practice may help focus medication education to the needs of the individual patient. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04815-5.

Depression is a common co-morbidity among rheumatoid arthritis (RA) patients, which may translate into difficulty performing activities of daily living. COVID-19 is an unprecedented disaster that has disrupted lives worldwide and led to a rise in the incidence of mental health disorders. Given the widespread economic devastation due to COVID-19, many RA patients, already susceptible to mental illness, maybe at an increased risk of inaccessibility to medical care, accentuated stress, and consequent worsening of existent mental health disorders, or the onset of new mental health disorders such as anxiety, post-traumatic stress disorder, or depression. The objective of this review is to assess if there is an increased risk of mental health disorders in patients with RA during the COVID-19 pandemic. Telemedicine has bridged the transition to remote chronic care in the pandemic period, though certain accessibility and technological challenges are to be addressed. Decreased access to care amid lockdowns and a proposed triggering of disease activity in patients with autoimmune disorders may potentially herald a massive spike in incidence or flares of patients diagnosed with RA in the coming months. Such a deluge of cases may be potentially devastating to an overburdened healthcare system. Rheumatologists may need to prepare for this eventuality and explore techniques to provide adequate care during these challenging times. The authors found that there is a significant association between the adverse impact on the mental health of RA patients and the COVID-19 pandemic. However, more research is needed to highlight individual risk factors.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular and extra-articular manifestations. Among extra-articular involvement, rheumatoid meningitis (RM) is a rare condition, which may exhibit variable symptoms including headache, focal and/or generalized neurologic deficits. It may develop as the preceding manifestation of RA or occur at any time of the disease course. Some drugs used for the treatment of RA may give rise to aseptic meningitis or create a tendency to infectious meningitis due to their immunosuppressive effect. All these possibilities may lead to difficulties in the differential diagnosis. Achieving a diagnosis in a short time is crucial in terms of prognosis. Here, we would like to report a case with longstanding RA manifested by left-sided weakness and seizure shortly after initiating etanercept (ETA) therapy. ETA-induced meningitis was confirmed with appropriate diagnostic tools. Our aim with this case-based review is to attract the attention of this rare condition and discuss diagnostic challenges.

To examine whether patients with inflammatory arthritis (IA) treated with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and/or biologic (b) DMARDs, could be affected from SARS-CoV-2 infection and to explore the COVID-19 disease course and outcome in this population. This is a prospective observational study. During the period February–December 2020, 443 patients with IA who were followed-up in the outpatient arthritis clinic were investigated. All patients were receiving cs and/or bDMARDs. During follow-up, the clinical, laboratory findings, comorbidities and drug side effects were all recorded and the treatment was adjusted or changed according to clinical manifestations and patient’s needs. There were 251 patients with rheumatoid arthritis (RA), 101 with psoriatic arthritis (PsA) and 91 with ankylosing spondylitis (AS). We identified 32 patients who contracted COVID-19 (17 RA, 8 PsA, 7 AS). All were in remission and all drugs were discontinued. They presented mild COVID-19 symptoms, expressed mainly with systemic manifestations and sore throat, while six presented olfactory dysfunction and gastrointestinal disturbances, and all of them had a favorable disease course. However, three patients were admitted to the hospital, two of them with respiratory symptoms and pneumonia and were treated appropriately with excellent clinical response and outcome. Patients with IA treated with cs and/or bDMARDs have almost the same disease course with the general population when contract COVID-19.

Janus kinase inhibitors (JAKi) are an exciting option for the treatment of rheumatoid arthritis (RA) but little is known about their safety and tolerability in patients with existing respiratory disorders. The objective was to compare pulmonary safety of JAKi versus rituximab in patients with concurrent interstitial lung disease (ILD) or bronchiectasis. We performed a retrospective electronic patient record review of patients with known ILD or bronchiectasis commencing JAKi or rituximab for the treatment of RA. Patients initiating treatment from January 2016 to February 2020 were included. Respiratory events (hospitalization or death from a respiratory cause) were compared using Kaplan–Meier survival analysis. We analysed patients who received JAKi (n = 28) and rituximab (n = 19) for a mean (SD) of 1.1 (0.62) and 2.14 (1) years respectively. Patients were predominantly female (68%), anti-CCP antibody positive (94%) and non-smoking (89%) with a median (IQR) percentage predicted FVC at baseline of 100% (82–115%) and percentage predicted TLCO of 62% (54.5–68%). Respiratory events occurred in five patients treated with JAKi (18%; 5 hospitalizations, 2 deaths) and in four patients treated with rituximab (21%; 3 hospitalizations, 1 death). Respiratory event rates did not differ between groups (Cox-regression proportional hazard ratio = 1.38, 95% CI 0.36–5.28; p = 0.64). In this retrospective study, JAKi for the treatment of RA with existing ILD or bronchiectasis did not increase the rate of hospitalization or death due to respiratory causes compared to those treated with rituximab. JAK inhibition may provide a relatively safe option for RA in such patients.

T-cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder characterized by a persistent increase in the number of large granular lymphocytes (LGLs), neutropenia, and splenomegaly. Clinical manifestations of T-LGLL in the setting of rheumatoid arthritis (RA) are often identical to those in which one would suspect Felty's syndrome (FS). These disorders are distinguished by the presence of T-cell clonality, which is present in T-LGLL but not in FS. Mutations in the signal transducer and activator of transcription 3 (STAT3) and 5b (STAT5b) genes can be used as molecular markers of T-LGLL, but their prevalence in FS is unknown.Eighty-one patients with RA and unexplained neutropenia or/and an increase in the number of LGLs above 2 × 109/L were stratified into RA-associated T-LGLL (N = 56) or FS (N = 25) groups based on the presence or absence of T-cell clonality. STAT3 and STAT5b gene mutations were assessed in each group by means of allele-specific polymerase chain reaction assays. Clinical, immunological, laboratory data and the results of immunophenotyping of blood and bone marrow lymphocytes were also evaluated.Mutations of the STAT3 gene and an increase in the number of LGLs above 2 × 109/L were detected in RA-associated T-LGLL, but not in FS (39% vs 0% and 21% vs 0%, respectively). Mutations in the STAT5b gene were not observed in either group. Expression of CD57, CD16, and CD5−/dim on CD3+CD8+ T-lymphocytes was observed in both RA-associated T-LGLL and FS.STAT3 gene mutations or LGL counts over 2 × 109/L in RA patients are indicative of T-LGLL.

The objective of the study was to compare the efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) between elderly-onset rheumatoid arthritis (EORA) and young-onset rheumatoid arthritis (YORA) patients. Patients with rheumatoid arthritis (RA) aged ≧18 years enrolled in a Japanese multicenter observational registry between 2009 and 2018 who had moderate or high disease activity when initiating bDMARDs were included. EORA was defined as RA with onset at 60 or over. After propensity score weighting for differences in confounding factors, generalized estimating equations were used to assess the relationship between the age of RA onset and bDMARD clinical effectiveness at 48 weeks after starting a bDMARD. Among a total of 7183 patients in the registry, 2815 (39.2%) were identified as EORA. The proportion of patients on bDMARDs was lower in the EORA as compared to the YORA (18.3% vs 28.0%, p

Although patient-reported outcome measures (PROMs) are recommended in clinical practice, their application in routine care is limited. The Rheumatoid Arthritis Foot Disease Activity Index (RADAI-F5) is a validated PROM for assessing foot disease in rheumatoid arthritis (RA). To explore patient and clinician opinions and perceptions of the clinical utility of the Rheumatoid Arthritis Foot Disease Activity Index (RADAI-F5), eight RA patients and eight clinicians routinely involved in the management of RA patients participated in one semi-structured remote video-based interview. They provided their perspectives on the barriers and facilitators to clinical implementation of the RADAI-F5. Three global themes were identified; 'Feet are a priority' as the impact of RA on the feet negatively impacted upon patient quality of life. The second theme was 'Need for a clinically feasible foot PROM' as participants recognised the current lack of a clinically feasible tool to determine RA foot disease. The third global theme of ‘Implementation’ was drawn together to form two subordinate themes: ‘Facilitators to RADAI-F5 implementation’ as the tool can promote communication, guide management, help screen foot symptoms, monitor foot disease status and treatments, and promote patient education and; ‘Barriers to RADAI-F5 implementation’ as there were associated practical difficulties, including lack of appointment time, administrative burdens, IT barriers and preference for further RADAI-F5 validation using imaging. The RADAI-F5 has significant potential as a clinical tool to aid foot disease management. However, implementation challenges must be overcome before broad adoption in rheumatology clinics.

Increased incidence of liver diseases emphasizes greater caution in prescribing antirheumatic drugs due to their hepatotoxicity. A transient elevation of transaminases to autoimmune hepatitis and acute liver failure has been described. For every 10 cases of alanine aminotransferase (ALT) elevation in a clinical trial, it is estimated that one case of more severe liver injury will develop once the investigated drug is widely available. Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (tsDMARDs) are less likely to cause liver damage. However, various manifestations, from a transient elevation of transaminases to autoimmune hepatitis and acute liver failure, have been described. Research on non-alcoholic fatty liver disease (NAFLD) has provided insight into a pre-existing liver disease that may be worsen by medication. Diabetes and obesity could be an additional burden in drug- induced liver injury (DILI). In the intertwining of the inflammatory and metabolic pathways, the most important cytokines are IL-6 and TNF alpha, which are also the cornerstone of biological treatment for rheumatoid arthritis. This narrative review evaluates the complexity and prevention of DILI in RA and treatment options involving biological therapy and tsDMARDs.

Nationwide lockdowns during SARS-CoV-2 (COVID-19) can compromise mental health and psychological wellbeing and limit opportunities for physical activity (PA), particularly in clinical populations, such as people with rheumatoid arthritis (RA), who are considered at risk for COVID-19 complications. This study aimed to investigate associations between PA and sedentary time (ST) with indicators of mental health and wellbeing in RA during COVID-19 lockdown, and examine the moderation effects of self-isolating. 345 RA patients completed an online questionnaire measuring PA (NIH-AARP Diet and Health Study Questionnaire), ST (International Physical Activity Questionnaire-Short Form), pain (McGill Pain Questionnaire and Visual Analogue Scale), fatigue (Multidimensional Fatigue Inventory), depressive and anxious symptoms (Hospital Anxiety and Depression Scale), and vitality (Subjective Vitality Scale) during the United Kingdom COVID-19 lockdown. Associations between PA and ST with mental health and wellbeing were examined using hierarchical multiple linear regressions. Light PA (LPA) was significantly negatively associated with mental fatigue (β = − .11), depressive symptoms (β = − .14), and positively with vitality (β = .13). Walking was negatively related to physical fatigue (β = − .11) and depressive symptoms (β = − .12) and positively with vitality (β = .15). Exercise was negatively associated with physical (β = − .19) and general (β = − .12) fatigue and depressive symptoms (β = − .09). ST was positively associated with physical fatigue (β = .19). Moderation analyses showed that LPA was related to lower mental fatigue and better vitality in people not self-isolating, and walking with lower physical fatigue in people self-isolating. These findings show the importance of encouraging PA for people with RA during a lockdown period for mental health and wellbeing.

Temporal artery biopsy (TAB) is one of the diagnostic criteria of giant cell arteritis (GCA) according to 1990 ACR criteria and remains a tool for diagnosis. Although clinicians perform TAB with an intent to confirm suspected GCA, some biopsies result in negative and some lead to non-GCA diagnoses. We aim to review the diagnoses after TAB biopsy performed for suspected GCA and also wanted to evaluate the diagnostic changes and concomitant diseases that develop over time. The patients who had undergone TAB for suspected GCA were identified using the record entry code for TAB. Patients meeting the classification criteria for GCA were designated as the GCA group and not meeting criteria were designated as a non-GCA group. Other classification criteria were implemented for the non-GCA group diseases. A total of 51 patients (Female: 62.7%, median age: 72.1 ± 7.4 years) who had undergone TAB for suspected GCA were evaluated. TAB was positive in 23 (69.6%) of the 33 patients who met the GCA classification criteria. No significant difference was found between TAB-positive and TAB-negative GCA patients in terms of clinical and laboratory parameters. In the non-GCA group, 12 patients had isolated polymyalgia rheumatica (PMR), and the diagnoses of the remaining six patients were as follows: four large vessel vasculitis (LVV) not satisfying GCA diagnostic criteria, one chronic myelomonocytic leukemia (CMML), and one amyloidosis. TAB was negative in all patients with isolated PMR. TAB showed primary amyloidosis in one patient. Out of 33 GCA patients, 21 had "isolated" GCA, four had GCA + Rheumatoid arthritis (RA), seven had GCA + PMR, and one had GCA + polymyositis. RA was diagnosed antecedent to GCA in two patients, and after GCA in the other two patients. One of the patients had developed GCA 20 years after polymyositis had been diagnosed. TAB was found to be positive in two-thirds of patients with suspected GCA. Late-onset RA and rarely other inflammatory rheumatic diseases may develop in the course of GCA.

Tumor necrosis factor inhibitor (TNFi) therapies are often the first biologic therapy used to treat rheumatoid arthritis (RA) patients. However, a substantial fraction of patients do not respond adequately to TNFi therapies. A test with the ability to predict response would inform therapeutic decision-making and improve clinical and financial outcomes. A 32-question decision-impact survey was conducted with 248 rheumatologists to gauge the perceived clinical utility of a novel test that predicts inadequate response to TNFi therapies in RA patients. Participants were informed about the predictive characteristics of the test and asked to indicate prescribing decisions based on four result scenarios. Overall, rheumatologists had a favorable view of the test: 80.2% agreed that it would improve medical decision-making, 92.3% said it would increase their confidence when making prescribing decisions, and 81.5% said it would be useful when considering TNFi therapies. Rheumatologists would be more likely to prescribe a TNFi therapy when the test reported that no signal of non-response was detected (79.8%) and less likely to prescribe a TNFi therapy when a signal of non-response was detected (11.3%–25.4%). Rheumatologists (84.7%) agreed that payers should provide coverage for such a test. This study shows that rheumatologists support the clinical need for a test to predict inadequate response to TNFi therapies. Test results were perceived to lead to changes in prescribing behaviors as results instill confidence in the ordering rheumatologist. Electronic supplementary material The online version of this article (10.1007/s00296-020-04746-7) contains supplementary material, which is available to authorized users.

To identify recommendations on the diagnosis and management of rheumatoid arthritis (RA) supported by low recommendation grades, to study the causes of this low grading, and to propose solutions. A group of six rheumatologists, with extensive experience in the development of systematic reviews, reviewed national and international RA recommendations and practice guidelines. They identified all recommendations with a low level of evidence or recommendation grade (levels equivalent to 4, 5, or grades C or D of the Oxford Levels of Evidence), classified them by areas (diagnosis, follow-up, treatment, others), and analyzed plausible causes of low graduation. A Delphi was used to select 10 recommendations where it was most important to obtain quality evidence to support them. Subsequently, actions were proposed to improve evidence and recommendation grading. Fourteen documents were analyzed, in which 192 recommendations with low evidence/grade of recommendation were identified, most of which were on treatment. The two most frequent causes of this low level are the absence of studies and the discrepancy between the wording of the recommendation and the evidence used. Finally, the proposed solution to the critical recommendations is a list of unanswered research questions and possible designs to answer them. We propose to design and promote research that truly supports or rectifies clinical practice and, thus, bridges the gap between existing evidence and critical recommendations.

Primary aim: Compare change in estimated cardiorespiratory fitness (eCRF change) in rheumatoid arthritis (RA) patients with population-based age- and sex-matched controls during ~ 11-year follow-up and identify variables associated with eCRF change. Secondary aim: Compare eCRF level in RA patients and controls. eCRF change from the second (HUNT2 1995–1997) to the third (HUNT3 2006–2008) surveys of the Norwegian Trøndelag Health Study was compared between RA patients (n = 188) and controls (n = 26,202) attending both surveys. Predictors of eCRF change were identified by Lasso regression followed by multiple linear regression. Mean eCRF level in RA patients (n = 436) and controls (n = 67,910) was compared using age-adjusted linear regression stratified on sex, as well as two-sample t tests including RA patients (n = 432) and controls (n = 59,124) who attended either HUNT2, HUNT3 or both HUNT2 and HUNT3. The mean eCRF decline from HUNT2 to HUNT3 in RA patients was 8.3 mL min−1 kg−1 versus 6.7 mL min−1 kg−1 in controls (p p p −1 kg−1; HUNT3: − 5.0 mL min−1 kg−1; men HUNT2: − 1.8 mL min−1 kg−1; HUNT3: − 4.0 mL min−1 kg−1. Higher age at baseline was associated with faster decline in eCRF. This change was more pronounced in RA patients than controls, indicating a larger negative effect on fitness of aging in RA. RA patients had lower eCRF compared to healthy individuals.