IntroductionAutoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage and serious long-term effects, like amyloidosis. Disease-specific anti-inflammatory therapeutic strategies are established for some AID. However, their clinical course frequently includes relapsing, uncontrolled conditions. Therefore, new therapeutic approaches are needed. Janus Kinase inhibitors (JAKi) block key cytokines of AID pathogenesis and can be a potential option.MethodsA systematic review of the literature in accordance with the PRISMA guidelines was conducted. Three databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) were searched for publications regarding the use of JAKi for AID. Data from the included publications was extracted and a narrative synthesis was performed. Criteria for defining treatment response were defined and applied.ResultsWe report data from 38 publications with a total of 101 patients describing the effects of JAKi in AID. Data on Type I Interferonopathies, Adult-Onset Still's Disease (AOSD), Systemic Juvenile Idiopathic Arthritis (sJIA), Familial Mediterranean Fever (FMF), and Behçet's Syndrome (BS) was identified. From a total of 52 patients with type I interferonopathies, in seven patients (7/52, 13.5%) a complete response was achieved, most (35/52, 67.3%) showed a partial response and a minority (10/52, 19.2%) showed no treatment response. For AOSD, a complete or a partial response was achieved by eleven (11/26, 42.3%) patients each. Two sJIA patients achieved complete response (2/4, 50%) and in two cases (2/4, 50%) a partial response was reported. Half of FMF patients showed a complete response and the other half had a partial one (3/6, 50.0%). Amongst BS patients most achieved a partial response (8/13, 61.5%). Five patients showed no response to therapy (5/13, 38.5%). Overall, the most frequent AEs were upper respiratory tract infections (17), pneumonia (10), BK virus viremia (10) and viruria (4), herpes zoster infection (5), viral gastroenteritis (2) and other infections (4).ConclusionThe results from this systematic review show that JAKi can be beneficial in certain AID. The risk of AEs, especially viral infections, should be considered. To accurately assess the risk benefit ratio of JAKi for AID, clinical trials should be conducted.

Objectives To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Methods A protocolized systematic review according to PRISMA guidelines was performed. Three databases were searched for reports on treatment strategies for VEXAS. Data from the included publications was extracted and a narrative synthesis was performed. Treatment response was recorded as complete (CR), partial (PR) or none (NR) depending on changes in clinical symptoms and laboratory parameters. Patient characteristics, safety data and previous treatments were analyzed. Results We identified 36 publications with a total of 116 patients, 113 (98.3%) were male. The identified reports included azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), JAK inhibitors (CR 11/33, 33%; PR 9/33, 27.3%), tocilizumab (CR 3/15, 20%; PR 6/15, 40%), allogeneic stem cell transplantation (alloSCT) (CR 6/7, 85.7%; one patient died), anakinra (CR 4/5, 80%; NR 1/5, 20%), canakinumab (CR ½, 50%; PR ½, 50%) and glucocorticoid monotherapy (CR 1/6, 16.7%; PR 4/6, 66.7%). Individual reports were available for TNF-inhibitors, rituximab, and methotrexate. Data on adverse events were available for 67 patients (67/116, 57.8%) and included: pneumonia (12/67, 17.9%), other infections (9/67, 13.4%), venous thromboembolisms (VTE) (6/67, 8.9%), cytopenias (4/67, 6.7%), acute (4/67, 5.9%) and chronic graft-versus-host-disease (2/67, 2.9%). Conclusion Current data on VEXAS treatment are limited and inhomogeneous. Treatment decisions should be individualized. For the devolvement of treatment algorithms clinical trials are needed. AEs remain a challenge, especially an elevated risk for venous thromboembolism associated to JAKi treatment should be carefully considered.

ZusammenfassungColchicin, das Gift der Herbstzeitlosen, hat verschiedene antiinflammatorische Effekte. Aus diesem Grund kommt es zur Behandlung von rheumatologischen Erkrankungen aus dem autoinflammatorischen Formenkreis, wie z. B. der Arthritis urica oder dem familiären Mittelmeerfieber (FMF), zum Einsatz. Darüber hinaus gibt es erste Daten, die einen positiven Nutzen von Colchicin bei kardiovaskulären Erkrankungen nahelegen. Des Weiteren werden aktuell verschiedene antiinflammatorische Therapieansätze in der COVID-19-Behandlung in Studien erprobt. Hier gibt es ebenfalls erste Publikationen, die einen potenziellen Nutzen von Colchicin in bestimmten Krankheitsphasen der Virusinfektion nahe legen. Dieser Beitrag will einen Überblick über die Wirkweise, den Nutzen und Nebenwirkungen sowie die verschiedenen Einsatzmöglichkeiten von Colchicin in der Rheumatologie geben. Weiterhin soll ein kurzer Ausblick in neue Einsatzgebiete dieses Medikamentes gegeben werden.

Objectives To study the safety and efficacy of long-term low dose glucocorticoids (GCs) in rheumatoid arthritis (RA). Methods A protocolised (PROSPERO [CRD42021252528]) systematic review and meta-analysis of double-blind, placebo-controlled randomised trials (RCTs) comparing a low dose of GCs (≤ 7.5mg/day prednisone) to placebo over at least two years was performed. The primary outcome was adverse events (AEs). We performed random-effects meta-analyses and used the Cochrane RoB tool and GRADE to assess risk of bias and quality of evidence (QoE). Results Six trials with 1,078 participants were included. There was no evidence of an increased risk of AEs (incidence rate ratio 1.08; 95%CI 0.86 to 1.34; p = 0.52), however, QoE was low. The risks of death, serious AEs, withdrawals due to AEs, and AEs of special interest were not different from placebo (very low to moderate QoE). Infections occurred more frequently with GCs (risk ratio 1.4; 1.19 to 1.65; moderate QoE). Concerning benefit, we found moderate to high quality evidence of improvement in disease activity (DAS28: -0.23; -0.43 to -0.03), function (HAQ -0.09; -0.18 to 0.00), and Larsen scores (-4.61; -7.52 to -1.69). In other efficacy outcomes, including Sharp van der Heijde scores, there was no evidence of benefits with GCs. Conclusion There is very low to moderate QoE for no harm with long-term low dose GCs in RA, except for an increased risk of infections in GC users. The benefit-risk ratio might be reasonable for using low-dose long-term GCs considering the moderate to high quality evidence for disease-modifying properties.

No abstract