[Biologicals and small molecules for systemic lupus erythematosus]. / Biologika und "small molecules" beim systemischen Lupus erythematodes.

Targeted treatment is a rheumatologist's dream, which, with the advent of biologicals and more recently small molecules, has become true for rheumatoid arthritis and is about to translate into reality for systemic lupus erythematosus (SLE). Belimumab, the first biological approved for SLE, is now also available in a subcutaneous formulation. It is notable that this drug achieved the primary endpoint in four independent trials and demonstrated substantial reduction of organ damage accrual. The B cell depletion with antibodies against CD20 remains clinically relevant and of interest for future developments and the combination of both approaches (belimumab and anti-CD20) is an exciting idea. Blockade of the type I interferon receptor with anifrolumab was effective in a phase 3 trial and blocking interleukin-12 and interleukin-23 with ustekinumab is currently being tested in a phase 3 clinical trial. The old ideas of blocking tumor necrosis factor (TNF) and interleukin­6 have also not yet been forgotten. More novel approaches comprise Janus kinase (Jak) inhibition with positive phase 2 data for baricitinib and soon inhibition of Bruton's tyrosine kinase (BTK) as well as proteasome inhibitors. The treatment of SLE could therefore soon become much more varied.

Early symptoms of systemic lupus erythematosus (SLE) recalled by 339 SLE patients.

Objective The European League Against Rheumatism and the American College of Rheumatology jointly embarked on a new classification criteria for systemic lupus erythematosus (SLE) project. Its first phase involved generation of a broad set of items potentially useful for classification of SLE. This study was undertaken to add the patient perspective to an expert Delphi approach and an early patient cohort study. Methods A national cross-sectional study was conducted. A self-report questionnaire was published in the "Schmetterling" (Butterfly), the quarterly journal of the German SLE patient association. Individuals with SLE were asked to anonymously complete the questionnaire, which asked for demographic details, organ manifestations, autoantibodies and symptoms. Results A total of 339 completed questionnaires out of 2498 were returned, a response rate of 13.6%; 83.2% reported they were ANA positive and 81.7% reported joint, 66.1% skin and 33.0% renal involvement. For the time before and in the first year after their SLE diagnosis, the majority reported fatigue (89.4%), joint pain (86.7%), photosensitivity (79.4%) and myalgia (76.1%). Of interest, more than half of the patients reported fever as an early symptom (53.7%). Conclusion For a Caucasian European SLE patient population, the overall characteristics suggest meaningful representation. While many symptoms were reported as expected, the high percentage of patients reporting fever and the significant number of patients with unexpected gastrointestinal complaints are of particular interest. These data add to the information on early SLE symptoms informing the development process of new SLE classification criteria.

[Tapering and termination of immunosuppressive therapy : Systemic lupus erythematosus]. / Ausschleichen und Beenden von immunsuppressiven Therapien : Systemischer Lupus erythematodes.

Similar to patients with other rheumatic diseases, patients with systemic lupus erythematosus (SLE) nowadays can also have the desire to terminate immunosuppressive and immunomodulatory medications. In order to provide appropriate advice to patients, the two main issues are the risk of severe adverse events under long-term therapy with any drug and the perceived risk of a flare, in particular of severe flares. The risks of long-term therapy vary greatly between drugs, ranging from severe unacceptable risks with cyclophosphamide and higher dose glucocorticoids to low risks usually outweighed by long-term benefits with hydroxychloroquine. The individual risk of flares is often difficult to estimate but clinical remission and at least 3 years of immunosuppression are recommended for lupus nephritis. The duration of remission can also be shorter in cases of milder forms of disease. This review article tries to put the available evidence into a clinical perspective and to derive concrete recommendations.

Toward new criteria for systemic lupus erythematosus-a standpoint.

While clearly different in their aims and means, classification and diagnosis both try to accurately label the disease patients are suffering from. For systemic lupus erythematosus (SLE), this is complicated by the multi-organ nature of the disease and by our incomplete understanding of its pathophysiology. Hallmarks of SLE are the presence of antinuclear antibodies (ANA), and multiple immune-mediated organ symptoms that are largely independent. In an attempt to overcome limitations of the current sets of SLE classification criteria, a new four-phase approach is being developed, which is jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). This review attempts to delineate the performance of the current sets of criteria, the reasons for the decision for classification, and not diagnostic, criteria, and to provide a background of the current approach taken.

[Rheumatoid arthritis today]. / Rheumatoide Arthritis/chronische Polyarthritis heute.

Advances in the therapy of rheumatoid arthritis with disease modifying antirheumatic drugs (DMARD) such as methotrexate and biological response modifiers in particular, have turned a chronic progressive disease with significant invalidity and mortality into one that can be well controlled. To prevent irreversible damage, early diagnosis is essential. DMARD therapy needs to be instituted within three months after symptom onset - a clinical and organisational challenge. Long term DMARD therapy is monitored using standardized scores and modified whenever not sufficiently successful. Analgesia, physiotherapy and occupational therapy as well as orthopaedic surgery play important roles in the management of rheumatoid arthritis. Consequent multimodal therapy can decisively influence the course of the disease and prevent or at least minimize damage.

[Early rheumatoid arthritis--rapid help is double help]. / Frühe rheumatoide Arthritis - wer schnell hilft, hilft doppelt.

Early diagnosis and therapy of persisting (or chronic) polyarthritis is essential for preventing permanent damage. The guidelines of the German Society for Rheumatology recommend referral to a rheumatologist 6 weeks (at the latest) after symptom onset. DMARD therapy should be initiated within 12 weeks. Even earlier, high titer rheumatoid factor, detectable antibodies to CCP, or early erosion, constitute firm arguments for initiating DMARD therapy in patients with arthritis. At this time point, fast acting combination therapy frequently achieves remission or at least low disease activity. Since TNF blockers are not commonly available for first line therapy, corticosteroids should accompany DMARD initiation. Sufficient capacity in early consultation at arthritis clinics, optimized communication with primary care physicians and sensibilisation of the entire population are essential to prevent permanent damage in as many patients as possible.

C-reactive protein is expressed and secreted by peripheral blood mononuclear cells.

C-reactive protein (CRP) protects against bacterial pathogens and is a predictor of cardiovascular events. CRP is produced by vascular and organ-specific cells but the generation of CRP from peripheral blood mononuclear cells (PBMC) is poorly established. In a randomized, double-blind, placebo-controlled, two-way cross-over trial six healthy volunteers received a bolus infusion of 20 IU/kg Escherichia coli endotoxin [lipopolysaccharide (LPS)] or placebo. Intracellular CRP protein and CRP secretion of peripheral blood mononuclear cells (PBMC) was measured at baseline and 6 h after LPS by flow cytometry and enzyme-linked immubosorbent assay (ELISA), respectively. CRP mRNA expression was determined by real-time polymerase chain reaction (PCR). Regulation of the expression pathway was assessed using specific inhibitors in vitro. Small amounts of CRP protein and mRNA were detectable in PBMC, which were up-regulated between two- and eightfold by endotoxaemia in vivo. Augmented expression and release of CRP by LPS was consistent in PBMC cell culture experiments. LPS, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha increased and IL-10 reduced CRP expression in PBMC. Toll-like receptor (TLR)-4, nuclear factor (NF)-kappaB and protein kinase C (PKC) activation were identified as intracellular signal transduction pathways of LPS-induced CRP expression. Constitutive CRP expression and release in PBMC is enhanced by inflammatory stimuli in vivo and in vitro. LPS might induce CRP generation via activation of TLR-4, NF-kappaB and PKC.