Treat to target and shared decision-making in systemic lupus erythematosus from the patients' perspective: results from an international patient survey.

OBJECTIVES: Treat-to-target (T2T) is being recognised as a promising concept to significantly improve the outcomes of patients with systemic lupus erythematosus (SLE). Despite its success being closely tied to patients' involvement, the patients' perspective regarding T2T has not been evaluated. We aimed to investigate patients' attitude towards T2T and their involvement in treatment decisions. METHODS: We designed a 13-question online survey on T2T, examining acceptance, willingness to participate in T2T trials, and potential obstacles. This was distributed amongst Dutch, Austrian, German, and Bulgarian patient organisations. RESULTS: In total, 863 patients participated of whom 48.4% reported being in remission, while 13% were uncertain about their remission status. Regarding shared decision-making, 62.1% reported being somewhat fully involved in treatment decisions, while 20.7% felt uninvolved. Shared decision-making was associated with disease duration, Dutch origin and satisfaction with treatment and remission. As for satisfaction with their health status, 56.2% were somewhat fully satisfied, while 29.3% were unsatisfied. 65.5% were satisfied with their treatment, 14.8% were not. Leading treatment goals were quality of life (QoL) normalisation (37.4%), organ damage prevention (24.6%) and absence of disease activity (22.6%). T2T was mainly seen positive with additional doctors' visits and initiation of new immunosuppressive drugs as potential disadvantages. CONCLUSIONS: T2T was perceived as beneficial with improvement of QoL as the most important treatment goal and the possibility of additional doctors' visits and initiation of new immunosuppressive agents as potential drawbacks. Patients unsatisfied with their health status and treatment may benefit from greater involvement in treatment decisions.

[Therapeutic antibodies in rheumatology]. / Therapeutische Antikörper in der Rheumatologie.

Emil von Behring's serum therapy for diphtheria was the first therapeutic use of antibodies. More than 100 years later, a new era in the treatment of rheumatic diseases began in 1998 with the approval of infliximab, an antibody directed against tumor necrosis factor alpha (TNF alpha). The special feature of antibody therapy is the ability to bind and neutralize antigens in a highly specific manner. In addition, target cells can be eliminated by activation of the immune system. These properties of the immune system are exploited in rheumatology to eliminate inflammatory cytokines or antibody-producing B lymphocytes. The tolerability is usually good but potential side effects, such as reactivation of tuberculosis with anti-TNF alpha treatment must be considered. Currently, 20 different antibodies and fusion proteins have been approved in Germany for the treatment of various inflammatory rheumatic diseases. Biosimilars can contribute to a price reduction after the patent protection expires. Many additional target antigens are being investigated and further structural innovations (e.g., bispecific antibodies, nanobodies or coupling with small molecules) are being developed.

EULAR recommendations for the management of systemic lupus erythematosus: 2023 update.

OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.

Defining the physician global assessment threshold equivalent to remission in patients with systemic lupus erythematosus.

OBJECTIVES: The optimal threshold of the physician global assessment (PGA) for remission in SLE has never been evaluated systematically. The aim of this study was to assess the ideal PGA threshold associated with physician remission and to investigate its impact on remission rates in our Lupus cohort. METHODS: In this monocentric cross-sectional study, patients with SLE were evaluated for physician remission by asking the treating physicians if they considered their patient in remission regardless of objective remission criteria. Further, two objective remission definitions were applied: 1) DORIS remission using a PGA of < 2 (0-10) (corresponding to < 0.5 on a VAS 0-3 used in DORIS); 2) DORIS remission with omission of PGA (modDORIS). A receiver operating characteristic analysis and regression analyses were performed to assess the ideal PGA threshold and factors influencing PGA. RESULTS: Of the 233 patients included, 126 patients (54.0%) were in physician remission, 42.5% in DORIS remission and 67.0% in modDORIS remission. A PGA of < 2 NRS 0-10) had the highest sensitivity (79%) and specificity (81%) for physician remission and modDORIS (AUC 0.85 and 0.69). PGA of patients fulfilling any of the remission definitions was associated with pain and hypocomplementemia. Damage was numerically higher in patients in modDORIS only; no association between PGA and damage was found in regression analysis. CONCLUSION: Using a PGA threshold of < 2 (0-10), corresponding to < 0.6 (0-3) resulted in best prediction of physician remission. PGA levels seem to be influenced by pain and complement levels but not disease damage.

'Status Quo' on Different Aspects of Gender Distribution in Rheumatology in Germany-Results from a Nationwide Online Survey among Physicians.

OBJECTIVES: Despite the increasing number of female medical students and fellows in Europe, women are still under-represented in higher academic careers and positions in medicine. The aim of this survey was to assess the 'status quo' on gender distribution among rheumatologists in Germany. METHODS: A web-based anonymous survey (21 questions with multiple answers and free text) using QuestionPro® was distributed among rheumatologists in Germany via newsletters, social media and personal contact, including questions regarding hierarchical positions and work characteristics. RESULTS: Among the total of 170 respondents (72% women, 28% men, 1% diverse), 48% were rheumatologists in training, 35% were trained rheumatologists and 7% were heads of rheumatology departments. Regarding the gender ratio at different hierarchical levels, 74% of respondents reported more men than women in leadership positions. Part-time work was possible in the departments of 86% of respondents, with more women working part-time (56%) compared to men (29%). Most respondents stated their impression that employees working part-time did not have the same career chances as full-time workers in their departments. In total, 66% agreed that activities to improve gender equity are necessary. The highest need was seen in reconciling work and family through, e.g., part-time models, flexible childcare options at work and a higher acceptance of part-time work in leadership positions. CONCLUSIONS: According to our results, a gender imbalance is prevalent among rheumatologists in Germany, with lower numbers of women evident at higher hierarchical levels. Traditional role assignments are still represented by a higher proportion of part-time work in women. The establishment of structural changes to achieve better gender equity is needed.

Determinants of patient and physician global assessments of disease activity in anti-neutrophil cytoplasmic antibody-associated vasculitis.

Objective: To compare physician and patient assessments of global disease activity in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and to identify associated factors. Methods: Global disease activity scores (0-10 points) were retrospectively analyzed from physicians and patients with AAV at each outpatient visit from 2010 to 2020. We compared the scores and performed a linear regression with a random effects to identify associated factors. Results: Patients (n = 143, 1,291 pairs, 52% female) had a mean 64 (±15) years of age and a mean disease duration of 9 (±7) years. Patients and physicians global disease activity assessments showed a moderate correlation (Pearson R 0.31, CI [0.23-0.52], p < 0.001). Linear regression showed a strong association between the physician-documented disease activity scores and serum CRP levels (ß = 0.22, CI [0.18, 0.28]), disease duration (ß = -0.022, CI [-0.04,-0.01]) and patients' assessment of disease activity (ß = 0.08, CI [0.04, 0.12]). By contrast, patient assessments were strongly associated with the degree of pain (ß = 0.30, CI [0.25, 0.35]), functional limitations in daily living (HAQ, ß = 0.49, CI [0.21, 0.78]) and the global physical well-being (NRS, ß = 0.39, CI [0.32, 0.46]). Conclusion: Patients' and physicians' assessments of disease activity correlated. High CRP levels and disease duration were associated with physician-assessed disease activity scores, while subjective limitations were associated with higher patient-assessed disease activity scores. These findings highlight and support the need to develop and evaluate patient-reported outcomes to assess disease activity in patients diagnosed with AAV.

[Acceptance of video consultation among patients with inflammatory rheumatic diseases depends on gender and location-Results of an online survey among patients and physicians]. / Akzeptanz der Videosprechstunde unter Patienten/innen mit entzündlich rheumatischen Erkrankungen ist geschlechts- und ortsabhängig ­ Ergebnisse einer Online-Umfrage unter Patienten/innen und Ärzten/innen.

INTRODUCTION: In order to successfully integrate telemedicine into the daily routine of rheumatology, both the patient's and the physician's perspective are important. For this purpose, a detailed study by means of a web-based survey was conducted by the Working Group Young Rheumatology (AGJR) of the German Society for Rheumatology (DGRh) and the German Rheumatism League National Association. By means of subgroup analysis of the data regarding video consultation, the aim was now to find out which requirements and wishes patients and physicians have for video consultations. METHODS: The prospective survey was distributed via social media, QR code and email. Descriptive statistics and regression analysis related to video consultation were performed and correlations were shown. RESULTS: The data indicated positive attitudes toward video consultation on the part of both patients (n = 299) and rheumatologists (n = 129). A correlation between age and positive opinion of the video consultation was found among the patients (r = 0.161, p = 0.006), especially among female patients a positive approval of the video consultation was found with increasing age (r = 0.244, p < 0.001 to male patients: r = -0.190, p = 0.145). Regarding the travelling time to the treating rheumatologist, male patients found the video consultation more attractive with increasing travelling time (r = 0.229, p = 0.078). With respect to the wishes of patients and physicians, video consultation should be used primarily for follow-up or emergency appointments. Video consultation for initial appointments, on the other hand, was very rarely mentioned. CONCLUSION: During the COVID 19 pandemic, video consultation was increasingly popular among rheumatology patients as well as among rheumatologists.

[Lupus nephritis]. / Lupusnephritis.

Lupus nephritis (LN) is one of the most frequent organ manifestations of systemic lupus erythematosus. Urine analysis is suitable for screening and proteinuria or an active sediment with acanthocytes can be indicative for LN. The gold standard for confirming the diagnosis is a kidney biopsy. The type and extent of the histological alterations are decisive for treatment. The LN is histologically classified into six classes, whereby classes III, IV and V in particular require immunosuppressive treatment. The treatment of LN consists of the administration of hydroxychloroquine, angiotensin-converting enzyme (ACE) inhibitors for nephroprotection and further antihypertensive drugs in cases of arterial hypertension. For prognostically unfavorable forms of LN an immunosuppressive treatment is necessary and a variety of substances are available for this. The immunosuppressive treatment is spread over several years, whereby intensive treatment can mostly be de-escalated after 3-6 months. Despite good treatment options the risk of recurrence and also for chronic renal damage with terminal renal failure is elevated and continuous monitoring is absolutely necessary.

Digitally-supported patient-centered asynchronous outpatient follow-up in rheumatoid arthritis - an explorative qualitative study.

OBJECTIVE: A steadily increasing demand and decreasing number of rheumatologists push current rheumatology care to its limits. Long travel times and poor accessibility of rheumatologists present particular challenges for patients. Need-adapted, digitally supported, patient-centered and flexible models of care could contribute to maintaining high-quality patient care. This qualitative study was embedded in a randomized controlled trial (TELERA) investigating a new model of care consisting of the use of a medical app for ePRO (electronic patient-reported outcomes), a self-administered CRP (C-reactive protein) test, and joint self-examination in rheumatoid arthritis (RA) patients. The qualitative study aimed to explore experiences of RA patients and rheumatology staff regarding (1) current care and (2) the new care model. METHODS: The study included qualitative interviews with RA patients (n = 15), a focus group with patient representatives (n = 1), rheumatology nurses (n = 2), ambulatory rheumatologists (n = 2) and hospital-based rheumatologists (n = 3). Data was analyzed by qualitative content analysis. RESULTS: Participants described current follow-up care as burdensome. Patients in remission have to travel long distances. Despite pre-scheduled visits physicians lack questionnaire results and laboratory results to make informed shared decisions during face-to-face visits. Patients reported that using all study components (medical app for ePRO, self-performed CRP test and joint self-examination) was easy and helped them to better assess their disease condition. Parts of the validated questionnaire used in the trial (routine assessment of patient index data 3; RAPID3) seemed outdated or not clear enough for many patients. Patients wanted to be automatically contacted in case of abnormalities or at least have an app feature to request a call-back or chat. Financial and psychological barriers were identified among rheumatologists preventing them to stop automatically scheduling new appointments for patients in remission. Rheumatology nurses pointed to the potential lack of personal contact, which may limit the holistic care of RA-patients. CONCLUSION: The new care model enables more patient autonomy, allowing patients more control and flexibility at the same time. All components were well accepted and easy to carry out for patients. To ensure success, the model needs to be more responsive and allow seamless integration of education material. TRIAL REGISTRATION: The study was prospectively registered on 2021/04/09 at the German Registry for Clinical Trials (DRKS00024928).

Comparison of physician and artificial intelligence-based symptom checker diagnostic accuracy.

Symptom checkers are increasingly used to assess new symptoms and navigate the health care system. The aim of this study was to compare the accuracy of an artificial intelligence (AI)-based symptom checker (Ada) and physicians regarding the presence/absence of an inflammatory rheumatic disease (IRD). In this survey study, German-speaking physicians with prior rheumatology working experience were asked to determine IRD presence/absence and suggest diagnoses for 20 different real-world patient vignettes, which included only basic health and symptom-related medical history. IRD detection rate and suggested diagnoses of participants and Ada were compared to the gold standard, the final rheumatologists' diagnosis, reported on the discharge summary report. A total of 132 vignettes were completed by 33 physicians (mean rheumatology working experience 8.8 (SD 7.1) years). Ada's diagnostic accuracy (IRD) was significantly higher compared to physicians (70 vs 54%, p = 0.002) according to top diagnosis. Ada listed the correct diagnosis more often compared to physicians (54 vs 32%, p < 0.001) as top diagnosis as well as among the top 3 diagnoses (59 vs 42%, p < 0.001). Work experience was not related to suggesting the correct diagnosis or IRD status. Confined to basic health and symptom-related medical history, the diagnostic accuracy of physicians was lower compared to an AI-based symptom checker. These results highlight the potential of using symptom checkers early during the patient journey and importance of access to complete and sufficient patient information to establish a correct diagnosis.

Remote self-collection of capillary blood using upper arm devices for autoantibody analysis in patients with immune-mediated inflammatory rheumatic diseases.

OBJECTIVES: To evaluate the feasibility, accuracy, usability and acceptability of two upper arm self-sampling devices for measurement of autoantibodies and C reactive protein (CRP) levels in patients with immune-mediated rheumatic diseases (IMRDs). METHODS: 70 consecutive patients with IMRD with previously documented autoantibodies were assigned to supervised and unsupervised self-collection of capillary blood with the Tasso+ or TAP II device. Interchangeability of 17 biomarkers with standard venesection was assessed by: concordance, correlation, paired sample hypothesis testing and Bland-Altman plots. Patients completed an evaluation questionnaire, including the System Usability Scale (SUS) and Net Promoter Score (NPS). RESULTS: While 80.0% and 77.0% were able to safely and successfully collect capillary blood using the Tasso+ and TAP II within the first attempt, 69 of 70 (98.6%) patients were successful in collecting capillary blood within two attempts. Concordance between venous and capillary samples was high; 94.7% and 99.5% for positive and negative samples, respectively. For connective tissue disease screen, anti-Ro52 and anti-proteinase 3 autoantibody levels, no significant differences were observed. Self-sampling was less painful than standard venesection for the majority of patients (Tasso+: 71%; TAP II: 63%). Both devices were well accepted (NPS; both: +28%), usability was perceived as excellent (SUS; Tasso+: 88.6 of 100; TAP II: 86.0 of 100) and 48.6 %/62.9% of patients would prefer to use the Tasso+/TAP II, respectively, instead of a traditional venous blood collection. CONCLUSIONS: Remote self-collection of capillary blood using upper arm-based devices for autoantibody and CRP analysis in patients with autoimmune rheumatic diseases is feasible, accurate and well accepted among patients. TRIAL REGISTRATION NUMBER: WHO International Clinical Trials Registry (DRKS00024925).

Impact of low-dose acetylsalicylic acid on pregnancy outcome in systemic lupus erythematosus: results from a multicentre study.

OBJECTIVE: It is still a matter of debate whether low-dose acetylsalicylic acid (LDASA) should be prescribed to all patients with SLE during pregnancy. This study aimed at investigating the impact of LDASA on pregnancy outcomes in patients with SLE without history of renal involvement and without antiphospholipid antibodies (aPL). METHODS: This is a retrospective analysis of prospectively monitored pregnancies at seven rheumatology centres. Previous/current renal involvement and aPL positivity were the exclusion criteria. Adverse pregnancy outcome (APO) is the composite outcome of the study and included proteinuric pre-eclampsia, preterm delivery <37 weeks, small-for-gestational age infant, low birth weight <2500 g, intrauterine growth restriction and intrauterine fetal death after 12 weeks of gestation of a morphologically normal fetus. RESULTS: 216 pregnancies in 187 patients were included; 82 pregnancies (38.0%) were exposed to LDASA treatment. No differences in terms of age at conception, disease duration, clinical manifestations, comorbidities and disease flare during pregnancy were observed between patients taking LDASA and those who did not take LDASA during pregnancy. APO was observed in 65 cases (30.1%), including 13 cases (6.1%) of pre-eclampsia. The incidence of all complications was similar in the two groups. However, it is interesting to note that pre-eclampsia had lower frequency in patients taking LDASA versus those not taking LDASA (2.4% vs 8.3%, p=0.14). CONCLUSIONS: In pregnant patients with SLE without renal involvement and were aPL-negative, there is a low risk of severe obstetric complications, such as early pre-eclampsia. LDASA treatment does not provide a statistically significant advantage over these complications. However, a careful individual risk-benefit balance is warranted.

Association of common variable immunodeficiency and rare and complex connective tissue and musculoskeletal diseases. A systematic literature review.

OBJECTIVES: To perform a systematic literature review (SLR) on the association of common variable immunodeficiency (CVID) and rare and complex connective tissue and musculoskeletal diseases, namely systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), idiopathic inflammatory myopathies (IIM), systemic sclerosis (SSc), relapsing polychondritis, antiphospholipid syndrome, immunoglobulin (Ig) G4-related disease, as well as undifferentiated and mixed connective tissue disease. METHODS: An SLR on studies and cases about the association of CVID and rare and complex connective tissue and musculoskeletal diseases was performed. Animal studies were excluded. RESULTS: 170 publications fulfilled the inclusion criteria. Sjögren's syndrome was the most frequent connective tissue disease in CVID-patients. Most case reports exist on SLE and CVID with SLE mostly preceding the manifestation of CVID. Multiple cases were published reporting the concurrence of CVID and inclusion body myositis and single cases were found on CVID and antisynthetase syndrome, polymyositis, limited SSc and relapsing polychondritis, respectively. There are no cases of CVID and antiphospholipid syndrome, IgG4-related disease, as well as undifferentiated and mixed connective tissue disease. CONCLUSIONS: The concurrence of CVID and complex connective tissue and musculoskeletal diseases, especially SS, IIM, SSc and relapsing polychondritis is rare but relevant. The measurements of Ig-levels should be performed before the initiation of immunosuppressive therapy to allow for the differentiation of primary and secondary Ig-deficiency and substitute IG if necessary.

A broad look into the future of rheumatoid arthritis.

Despite all improvements in rheumatoid arthritis, we are still not able to prevent or cure the disease. Diagnostic delays due to lack of access to a specialist and costly therapies are still a major obstacle for many patients. Even in first-world countries, the treat-to-target principle and the goal of disease remission are often missed. Thus, rheumatoid arthritis (RA) is still the reason for disability and reduced quality of life for many patients. So, is it time to move the goalpost even further? Where are we heading next? And will we finally be able to cure the disease? These questions are addressed in our review article.