Response to SARS-CoV-2 vaccination in systemic autoimmune rheumatic disease depends on immunosuppressive regimen: a matched, prospective cohort study.

OBJECTIVE: To assess the humoral response to messenger RNA (mRNA) vaccine of patients with systemic autoimmune rheumatic disease (SARD) and the effect of immunosuppressive medication in a matched cohort study. METHODS: Patients with SARD were enrolled and matched 1:1 for sex and age with healthy control (HC) subjects. Differences in humoral response to two doses of an mRNA vaccine in terms of seroconversion rate (SCR) and SARS-CoV-2 antibody level between the two groups and the impact of treatment within patients with SARD were assessed. RESULTS: We enrolled 82 patients with SARD and 82 matched HC. SCR after the first dose was lower among the patient group than that of HC (65% compared with 100% in HC, p<0.0001) but levelled up after the second dose (94% vs 100%). After the second dose, SCR was lower for patients on combination disease-modifying antirheumatic drug (DMARD) therapy compared with all other groups (81% compared with 95% for monotherapy, p=0.01; 100% for both no DMARD therapy and HC, both p<0.0001). In addition, antibody levels after both doses were lower in patients compared with HC. We found that vaccination response was determined primarily by the number of DMARDs and/or glucocorticoids received, with patients receiving combination therapy (dual and triple therapy) showing the poorest response. CONCLUSIONS: Patients with SARD showed a good response after the second vaccination with an mRNA vaccine. However, the choice of immunosuppressive medication has a marked effect on both SCR and overall antibody level, and the number of different immunomodulatory therapies determines vaccination response.

Importance of the second SARS-CoV-2 vaccination dose for achieving serological response in patients with rheumatoid arthritis and seronegative spondyloarthritis.

OBJECTIVES: To assess the kinetics of humoral response after the first and second dose of messenger RNA (mRNA) vaccines in patients with inflammatory joint diseases compared with healthy controls (HC). To analyse factors influencing the quantity of the immune response. METHODS: We enrolled patients with rheumatoid arthritis (RA) and seronegative spondyloarthritis (SpA), excluding those receiving B-cell depleting therapies and assessed the humoral response to mRNA vaccines after the first and the second dose of the vaccine in terms of seroconversion rate and titre. We compared the results to a HC group and analysed the influence of therapies as well as other characteristics on the humoral response. RESULTS: Samples from 53 patients with RA, 46 patients with SpA and 169 healthy participants were analysed. Seroconversion rates after the first immunisation were only 54% in patients with inflammatory arthritis compared with 98% in the HC group. However, seroconversion rates were 100% in all groups after second immunisation. Patients developed reduced antibody titres after the first vaccination compared with HC, but there was no difference after the second dose. While disease modifying anti-rheumatic drug (DMARD) monotherapy did not affect antibody levels, seroconversion rates as well as titre levels were reduced in patients receiving a combination of DMARDs compared with HC. CONCLUSIONS: Patients with inflammatory joint diseases under DMARD therapy show impaired humoral responses to the first vaccine dose but excellent final responses to vaccination with mRNA vaccines. Therefore, the full course of two immunisations is necessary for efficient vaccination responses in patients with inflammatory arthritis under DMARD therapy.

Is the state of health of rheumatoid arthritis patients receiving adequate treatment, predictable? - Results of a survey.

BACKGROUND: A survey was conducted to evaluate whether a steady improvement in the quality of life of Rheumatoid Arthritis (RA) patients as frequently reported in clinical studies, does actually occur. The focus of this study laid on the personal perception of RA patients. How do patients who have been treated along accepted guidelines see the state of their health and their joint pain at different points in time? METHODS: RA patients were asked to complete a questionnaire and return it to an opinion research centre. The questionnaire, which was developed by the authors, was divided into the areas: demography, symptom description and medical care, as well as the illness in a personal context. Three telephone interviews followed in monthly intervals when the patients' feelings about their illness, their every-day coping mechanisms and their social lives were rated. Intra-subject correlation and the level of agreement among patients when assessed at three different points within a two month period, was determined. RESULTS: 127 patients replied to the questionnaire. RA exerts a significant impact on a patient's daily life. Average ratings of current state of health and joint pain (answered on a 5-part scale extending from 1 (very good) to 5 (very bad)) range between 2.6 and 2.9 all three times. However, intra-subject correlation between the different assessment times, is in general quite modest. Concerning the question: "How is your join pain today?" only 14 of 127 participants express identical ratings all three times , while in one third of the participants, a difference of two digits on the 5-part scale, at least twice had to be noticed. Intra-class correlation coefficients between answers at different points are often much smaller than 0.5. Results were similar in all subgroups analysed (men vs. women; patients receiving biologics vs. those not receiving biologics; disease duration ≤3 years vs. 4 to 10 years vs. ≥11 years). CONCLUSION: On an individual level personal assessments of health, well-being and joint pain are nevertheless unsteady even within the timeframe of two months. This is why, even now, RA patients still cannot plan their lives as non-affected people can.

Clinical implementation of musculoskeletal ultrasound in rheumatology in Austria.

The aim of the study is to assess the clinical implementation of musculoskeletal ultrasound (MSUS) in rheumatology in Austria. A survey was conducted among Austrian rheumatologists and physicians of other specialties with a focus on rheumatology. The questionnaire was designed by the members of the Austrian Radiology-Rheumatology Initiative for Musculoskeletal UltraSound including the following items: demographics, access to MSUS and MSUS training, application of MSUS to support diagnosis, monitoring and treatment decisions, and obstacles for the routine performance of MSUS. Eighty-eight (21.9 %) out of the 402 surveyed physicians responded. No access to MSUS and/or inadequate training in the technique was more commonly reported by senior (>50 years; 64.3 and 67.7 %, respectively) than by younger physicians (16.7 %, p = 0.01 and 18.5 %, p < 0.001, respectively). The lowest availability of sonography was found among senior rheumatologists (25.0 %, p = 0.001 compared to the total group). MSUS is routinely used for diagnosis and/or monitoring purposes by 12.5 % of physicians and 20.5 % perform sonography in clinically unclear cases. A limited number of physicians apply the method to support treatment decisions and/or to evaluate treatment success. The most important obstacles for routine application of MSUS in rheumatology are limited access to ultrasound machines, lack of training/education in the technique, and time constraints in daily routine. Low access to high-end ultrasound devices, lack of training, and time constraints may explain the low appreciation of MSUS among Austrian physicians evaluating patients with rheumatic diseases.

The accelerated waning of immunity and reduced effect of booster in patients treated with bDMARD and tsDMARD after SARS-CoV-2 mRNA vaccination.

Objectives: This study aimed to assess the duration of humoral responses after two doses of SARS-CoV-2 mRNA vaccines in patients with inflammatory joint diseases and IBD and booster vaccination compared with healthy controls. It also aimed to analyze factors influencing the quantity and quality of the immune response. Methods: We enrolled 41 patients with rheumatoid arthritis (RA), 35 with seronegative spondyloarthritis (SpA), and 41 suffering from inflammatory bowel disease (IBD), excluding those receiving B-cell-depleting therapies. We assessed total anti-SARS-CoV-2 spike antibodies (Abs) and neutralizing Ab titers 6 months after two and then after three doses of mRNA vaccines compared with healthy controls. We analyzed the influence of therapies on the humoral response. Results: Patients receiving biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) showed reduced anti-SARS-CoV-2 S Abs and neutralizing Ab titers compared with HC or patients receiving conventional synthetic (cs)DMARDs 6 months after the first two vaccination doses. Anti-SARS-CoV-2 S titers of patients with b/tsDMARDs declined more rapidly, leading to a significant reduction in the duration of vaccination-induced immunity after two doses of SARS-CoV-2 mRNA vaccines. While 23% of HC and 19% of patients receiving csDMARDs were without detectable neutralizing Abs 6 months after the first two vaccination doses, this number was 62% in patients receiving b/tsDMARDs and 52% in patients receiving a combination of csDMARDs and b/tsDMARDs. Booster vaccination led to increased anti-SARS-CoV-2 S Abs in all HC and patients. However, anti-SARS-CoV-2 S Abs after booster vaccination was diminished in patients receiving b/tsDMARDs, either alone or in combination with csDMARDs compared to HC. Conclusion: Patients receiving b/tsDMARDs have significantly reduced Abs and neutralizing Ab titers 6 months after mRNA vaccination against SARS-CoV-2. This was due to a faster decline in Ab levels, indicating a significantly reduced duration of vaccination-induced immunity compared with HC or patients receiving csDMARDs. In addition, they display a reduced response to a booster vaccination, warranting earlier booster vaccination strategies in patients under b/tsDMARD therapy, according to their specific Ab levels.

Diagnosis, differential diagnosis and treatment of polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a common disorder in the elderly population. The diagnosis is based upon recognition of a clinical syndrome, consisting of pain and stiffness in the shoulder and pelvic girdle, muscle tenderness of the upper and lower limbs and nonspecific somatic complaints. In addition, in most cases the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentration are highly elevated. Although PMR and giant cell arteritis (GCA) are commonly regarded as two clinical variations of the same disease, their clinical picture is quite different. Whilst in PMR the musculoskeletal symptoms predominate, the major features of GCA are arterial inflammation and its consequences, which suggests clinical and pathological discrepancies between the two syndromes and important differences with respect to morbidity and mortality. The prognosis of correctly diagnosed PMR is excellent. It is well known that corticosteroid therapy in PMR usually leads to rapid and dramatic improvement of patients' complaints and returns them to previous functional status. However, prolonged corticosteroid treatment, sometimes for several years, may be necessary to maintain clinical improvement. Despite all the knowledge about the beneficial effects of corticosteroid treatment, data concerning the optimal dosage regimen are lacking. Long-term corticosteroid use can be associated with various adverse events, of which induction of osteoporosis, diabetes mellitus and infection among the worst. A Corticosteroid Side Effect Questionnaire has been shown to dose-dependently detect adverse effects perceived by patients. The European League Against Rheumatism (EULAR) response criteria for PMR comprise a core set of markers for monitoring therapeutic responses in PMR, namely ESR or CRP, the visual analogue scale of patient's pain and physician's global assessment, as well as morning stiffness and the ability to elevate the upper limbs. The PMR-disease activity score has been developed on the basis of EULAR response criteria as a means of expressing disease activity as an absolute number. A score <7 indicates low disease activity, scores 7-17 suggest medium activity, and a score >17 is indicative of high disease activity. The PMR-disease activity score has been proven to be highly correlated with patient's global assessment, patient satisfaction and ESR. It provides an easily applicable and valid tool for disease activity monitoring in patients with PMR. Improved knowledge of disease activity processes, exact monitoring of disease activity and treatment responses, and increased risk-estimation of treatment schedules should ultimately improve the care of patients with PMR.

[Recommendations of the Austrian Society of Rheumatology/Austrian Radiology-Rheumatology Initiative for Musculoskeletal Ultrasound for the application of ultrasound in rheumatology]. / Empfehlungen der Österreichische Gesellschaft für Rheumatologie und Rehabilitation/Austrian Radiology-Rheumatology Initiative for Musculoskeletal Ultrasound zur Anwendung des Ultraschalls bei rheumatischen Erkrankungen in der klinischen Praxis.

It is the current goal in rheumatology to diagnose and treat inflammatory rheumatic diseases early in order to avoid structural damage. Functional imaging methods such as musculoskeletal sonography are increasingly used to support the clinical diagnosis. To ascertain the quality of ultrasound assessments performed by rheumatologists in Austria, the Austrian Radiology-Rheumatology Initiative for Musculoskeletal Ultrasound (ARRIMUS) proposed recommendations for a training curriculum, technical standards for ultrasound equipment, minimum requirements for documentation, indications for sonography and the use of ultrasound for interventions. These recommendations have been endorsed by the Austrian Society of Rheumatology and should aid rheumatologists to perform high quality ultrasound assessment in clinical practice.

Quality of care of rural rheumatoid arthritis patients in Austria.

OBJECTIVES: To determine how fast rheumatoid arthritis (RA) was diagnosed in a group of patients in a rural area and whether medical care and patient satisfaction were adequate in a predominantly non-urban settlement. METHODS: When visiting their rheumatologist, patients with RA were asked to complete a questionnaire at home after the consultation and then return it to an independent opinion research centre, where the data were collected and analysed. The form comprised various areas, namely demography, aspects of the diagnosis, medical care, therapeutic measures and the illness in a personal context. RESULTS: Of 150 patients, 127 answered the questionnaire. A total of 63 % of the patients lived in settlements of less than 5,000 inhabitants, and a further 18 % in settlements of more than 5,000-50,000 inhabitants. The rheumatologist attended could be reached within 1 h for 90 % of the patients. In slightly fewer than 30 % of the respondents, the diagnosis of RA was made within 3 months, and in 44%, within 6 months. In 75 %, the diagnosis was made by a rheumatologist. After experiencing the first symptoms, 80 % of the respondents contacted their general practitioner. A high degree of satisfaction appears to originate from the information supplied by the rheumatologist attended. Most patients believed they were involved in decision making regarding their therapy. CONCLUSION: The majority of the respondents came from rural areas. RA was diagnosed within 6 months for almost half of the patients questioned. Most patients believed they were well informed and involved in therapeutic decision making.

Patient-centered rheumatoid arthritis disease activity assessment by a modified RADAI.

OBJECTIVE: To evaluate the psychometric properties and validity of a modified version of the Rheumatoid Arthritis Disease Activity Index (RADAI) without joint counts in order to facilitate rapid and easy RA activity assessment in daily routine. METHODS: One hundred sixty-nine outpatients with RA completed the original RADAI and the modified RADAI-5. Simultaneously, the Disease Activity Score-28-erythrocyte sedimentation rate (DAS28-ESR) and C-reactive protein (DAS28-CRP) and the Simplified Disease Activity Index (SDAI) and Clinical DAI (CDAI) were applied. Cronbach's alpha, as a measure for internal consistency, and Spearman's rho, to evaluate the linear relationship of the different disease activity scales, were calculated. Rho was determined for the RADAI-5 and the core set measures to assess convergent validity. For agreement analysis, kappa statistics were calculated. An attempt was made to estimate the modified questionnaire's sensitivity to change. RESULTS: Means for the RADAI and the RADAI-5 were 2.8 (range 0.0-9.12) and 3.07 (0-10), respectively. Other means were as follows: DAS28-ESR 3.51 (0.28-6.67), DAS28-CRP 3.19 (1.12-5.83), CDAI 11.53 (0.0-44.6), and SDAI 12.36 (0.1-44.9). Cronbach's alpha was highest for the RADAI-5 (0.917) and lowest for the DAS28-CRP (0.510). The RADAI-5 was highly significantly correlated (all p < 0.0001) to all other instruments. However, kappa was < 0.65 for the relation of the RADAI-5 and all other scores except the RADAI. Changes of the RADAI-5, DAS28-ESR, and CDAI were significantly correlated (p < 0.001). CONCLUSION: The RADAI-5, refraining from joint counts, was shown to be capable of measuring RA activity. Reliability and convergent validity could be proven.

The Disease Activity Score in 28 joints in rheumatoid arthritis and psoriatic arthritis patients.

OBJECTIVE: To assess the factorial structure of the Disease Activity Score including a 28-joint count (DAS28) if applied in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: DAS28 values from 85 consecutive PsA outpatients and 2 RA patient cohorts comprising 85 patients each were compared. The first RA cohort (RA1) consisted of age- and sex-matched patients seen during the same period as the patients with PsA. The first 85 RA outpatients from September 2003 were included in the second cohort (RA2). Item weighting, factor loading, and internal consistency were assessed by factor analysis, principal component analysis, and calculation of Cronbach's alpha. RESULTS: The mean +/- SD DAS28 scores of patients in the PsA, RA1, and RA2 cohorts were 3.2 +/- 1.31, 3.21 +/- 1.45, and 3.79 +/- 1.44, respectively. A significant difference between the PsA and RA2 cohorts was found for DAS28 (P = 0.0063), swollen joint count (P = 0.007), and patient's global assessment (P < 0.001), but not for erythrocyte sedimentation rate. Internal consistency of the DAS28 in patients with PsA was considerably lower, item weighting showed remarkable differences, and factor analysis revealed that the DAS28 constitutes a bidimensional instrument in patients with PsA, whereas in both RA cohorts it appeared to be monodimensional. CONCLUSION: With respect to its statistical properties, the DAS28 proved to be considerably different in PsA compared with RA. Therefore its application for disease activity assessment in patients with PsA cannot be recommended without a formal validation procedure.

Disease activity score-28 values differ considerably depending on patient's pain perception and sex.

OBJECTIVE: To determine if the Disease Activity Index including a 28-joint count (DAS28) is equally applicable for the total population with rheumatoid arthritis (RA). METHODS: Five hundred fifty-seven outpatients with RA [432 women, 125 men; median age 64 yrs (range 0-85), median disease duration 48 mo (range 2-548)] were enrolled consecutively into this cross-sectional study. DAS28, physician's global assessment of disease activity, patient's assessment of pain on visual analog scale, C-reactive protein (mg/dl), rheumatoid factor (RF), and disease duration were recorded. t-tests were applied for all comparisons of DAS28 values. Linear regression analysis was performed for each confounding factor. RESULTS: The mean DAS28 in female patients was 3.66 +/- 0.57 SEM, and in males 3.01 +/- 1.12 (p < 0.001). DAS values in patients with early RA (< 37 mo) were significantly higher than in patients with advanced RA (3.62 +/- 0.67 vs 3.37 +/- 0.81, respectively; p < 0.017). Regression analysis revealed a highly significant relationship between DAS28 score and patient's pain rating (r = 0.592, p < 0.0001). Pain exerted the greatest influence on the DAS28 (p < 0.0001), while of the other factors only age (p < 0.008 for females, p < 0.007 for males) was also significantly correlated with the DAS28 values. CONCLUSION: DAS28 values differ considerably depending primarily on the patient's pain perception and gender and to a lesser degree on patient's age, whereas results for disease duration and RF were inconclusive.

Disease activity measurement of rheumatoid arthritis: Comparison of the simplified disease activity index (SDAI) and the disease activity score including 28 joints (DAS28) in daily routine.

OBJECTIVE: To assess the reliability and congruency of the Simplified Disease Activity Index (SDAI) compared with the Disease Activity Score including 28 joints (DAS28) in daily practice. METHODS: In 399 consecutive rheumatoid arthritis patients (307 women, 92 men), the SDAI and the DAS28 were calculated. Additionally, 115 of them were observed for 1 year and changes of both values were recorded. Joint assessments were performed by 4 experienced physicians. DAS28 and SDAI values and the respective changes were compared by correlation and regression analyses. Reliability assessment and factor analyses were performed. Disease activity categorizing was compared by the Wilcoxon's rank sum test. RESULTS: The median +/- SD scores were 3.42 +/- 1.45 for the DAS28 and 11.50 +/- 11.50 for the SDAI. Spearman's rho was 0.897 (P < 0.0001). Score changes were also significantly correlated. Reliability testing and factor analysis revealed that both scores can be regarded as monocomponent. Categorizing patients according to the European League Against Rheumatism response criteria (EULARC) or the SDAI revealed statistically significant differences between the 2 scales (P < 0.0001). CONCLUSION: SDAI values are considerably shifted to the left compared with DAS28 levels. Internal consistency and reliability of both scores are comparable. For the differences in disease activity categorizing due to the SDAI compared with the EULARC, a major limitation of the application of this newly developed disease activity score is given, unless these incongruencies can be cleared.