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treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn.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.

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.

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.

[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.

[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.

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.

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.

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).

[Innovations in the pharmaceutical treatment of systemic lupus erythematosus]. / Innovationen in der Arzneimitteltherapie des systemischen Lupus erythematodes.

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous disease with a complex pathogenesis. Until now, the choice of therapeutic agents has been limited. OBJECTIVE: This review revisits known forms of treatment for SLE and introduces new recently approved agents and agents currently under investigation in clinical trials. The aim of this article is to map the current data from phase 2 and phase 3 studies and European recommendations for the management of SLE and to provide an outlook on the future of lupus treatment. DATA SITUATION: As the focus of SLE treatment is on the achievement of remission with low steroid dosages, early and effective immunosuppressive therapy is essential. With the interferon type I receptor antagonist anifroluma, a treatment for extrarenal lupus has been approved for the first time since 2011. For lupus nephritis, the well-known belimumab (approval by the U.S. Food and Drug Administration, FDA and the European Medicines Agency, EMA) and the calcineurin inhibitor voclosporin (FDA) are newly available. In addition, a large number of substances are currently undergoing clinical trials, e.g. the CD-20 inhibitor obinutuzumab, Janus kinase inhibitors and low-dose interleukin­2. CONCLUSION: New and innovative treatment concepts are finding their way into lupus treatment and other promising substances are in the pipeline; however, only long-term data will show to what extent these improve the long-term outcome of patients. Nevertheless, these are important and much needed advances in the treatment of SLE.

Remission in SLE-do DORIS criteria match the treating physician's judgment? A cross-sectional study to assess reasons for discordance.

OBJECTIVES: The definition of an accurate target for a treat-to-target approach in SLE has been challenging over past years, and recently the DORIS definitions of remission were presented by the international DORIS task force. It was our aim to assess the frequency of DORIS remission and LLDAS in our SLE cohort and their agreement with the treating physician's (DORIS-) independent remission judgement. Patient characteristics leading to lack of agreement and incoherence ought to be identified. METHODS: In this monocentric cross-sectional study, patients with SLE were enrolled and assessed between September 2016 and December 2017. DORIS remission definitions were applied and after the clinical consultation, the treating physicians gave his/her opinion on whether the patient was in remission. Regression analyses were performed to identify parameters influencing physician remission. RESULTS: A total of 233 patients were included (87.6% female); 99 (42.5%) patients fulfilled any of the four DORIS remission definitions, while 126 patients were in remission according to their physician's judgement. We observed discordance in the assessment of remission in 53 patients (22.7%). Physician remission was influenced by disease activity [odds ratio (OR) 0.76, 95% CI: 0.63, 0.90], disease and/or treatment-related damage (OR 0.78, 95% CI: 0.62, 0.98) and the presence of ds-DNA antibodies (OR 2.47, 95% CI: 1.06, 6.04). CONCLUSIONS: DORIS remission proved an achievable target in our outpatient clinic. Still we found discordance regarding DORIS remission and the treating physician's judgement with a greater number of patients considered in remission by their physicians.

Are remission and low disease activity state ideal targets for pregnancy planning in systemic lupus erythematosus? A multicentre study.

OBJECTIVES: To determine whether disease remission or low disease activity state at the beginning of pregnancy in SLE patients is associated with better pregnancy outcome. METHODS: Pregnancies in SLE patients prospectively monitored by pregnancy clinics at four rheumatology centres were enrolled. Patient demographics and clinical information were collected at baseline (pregnancy visit before 8 weeks of gestation) including whether patients were in remission according to the Definition of Remission in SLE (DORIS) criteria and and/or Lupus Low Disease Activity State (LLDAS). Univariate and multivariate analysis were performed to determine predictors of disease flare and adverse pregnancy outcomes (APOs) including preeclampsia, preterm delivery, small for gestational age infant, intrauterine growth restriction and intrauterine fetal death. RESULTS: A total of 347 pregnancies were observed in 281 SLE patients. Excluding early pregnancy losses, 212 pregnancies (69.7%) occurred in patients who were in remission at baseline, 33 (10.9%) in patients in LLDAS, and the remainder in active patients. Seventy-three flares (24%) were observed during pregnancy or puerperium, and 105 (34.5%) APOs occurred. Multivariate analysis revealed that patients in disease remission or taking HCQ were less likely to have disease flare, while a history of LN increased the risk. The risk of APOs was increased in patients with shorter disease duration, while being on HCQ resulted a protective variable. An almost significant association between complete remission and a decreased risk of APOs was observed. CONCLUSIONS: Prenatal planning with a firm treat-to-target goal of disease remission is an important strategy to reduce the risk of disease flares and severe obstetric complications in SLE pregnancies.