In this randomized trial, patients with vasculitides who were in complete remission after initial induction therapy received either rituximab at intervals or daily azathioprine. More patients had ...sustained remission with rituximab than with azathioprine.
Granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis), microscopic polyangiitis, and renal-limited antineutrophil cytoplasm antibody (ANCA)–associated vasculitides are the main ANCA-associated vasculitis variants.
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Although these entities differ in their pathogenesis, genetics, and serotypes, severe forms of ANCA-associated vasculitis share several clinical features and currently have similar treatments.
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A staged therapeutic strategy that combines glucocorticoids and cyclophosphamide to induce remission has dramatically improved survival over the past few decades, but with frequent early and late side effects. The results of two trials (RAVE and RITUXVAS) showed that rituximab was not inferior to daily oral or pulse intravenous cyclophosphamide for the induction . . .
Summary
Thrombopoietin‐receptor agonists (Tpo‐RAs) are highly effective in immune thrombocytopenia (ITP). Recently, cases of durable remission after Tpo‐RA discontinuation in adult ITP have been ...reported. We aimed to describe the subset of patients in whom transient Tpo‐RA therapy may induce a durable response. We studied all adults with primary ITP treated with at least one Tpo‐RA over a 5‐year period (n = 54) and seen at one of three participating referral centres in France. Tpo‐RAs were discontinued in 20 of 28 patients who achieved a complete response. We excluded six patients because a previous treatment at the start of Tpo‐RA treatment may have interfered with the response. Overall, eight patients with chronic ITP showed a sustained response median follow‐up: 13·5 months (range 5–27 months). We could not identify a predictive factor of sustained response. In conclusion, a substantial proportion of ITP patients receiving Tpo‐RAs can maintain a durable response after treatment discontinuation.
The recent large decrease in splenectomy use for chronic immune thrombocytopenia (ITP) is partly due to still-unsolved questions about long-term safety. We performed the first single-center ...exposed/unexposed cohort study evaluating the long-term incidence of splenectomy complications in patients with primary ITP. Overall, 83 patients who underwent splenectomy more than 10 years ago (exposed) were matched with 83 nonsplenectomized patients (unexposed) on the date of ITP diagnosis ±5 years, age and gender. After a median follow-up of 192 months (range 0.5-528), 43 patients (52%) achieved overall response after splenectomy. Splenectomized patients experienced more venous thromboembolism (VTE) than controls (n = 13 vs n = 2, P = 0.005). On multivariate analysis, splenectomy was an independent risk factor of VTE (hazard ratio = 4.006, P = 0.032 95% confidence interval: 1.13-14.21). Splenectomized patients presented more severe infections on long-term follow-up: all required hospitalization, and 5/26 (19%) infections led to severe sepsis or septic shock and to death for 3 cases (none in controls). However, the incidence of malignancy was similar in both groups, as was cardiovascular risk, which appeared to be related more to ITP than splenectomy. Finally, splenectomy did not significantly decrease overall survival. Despite the risk of thrombosis and severe sepsis, splenectomy remains an effective and curative treatment for ITP.
Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to splenectomy and the requirement for long-term treatment to reduce the risk of significant bleeding ...events. In this multicenter study, we included 37 patients with multirefractory ITP, defined as no response to splenectomy, rituximab, romiplostim, and eltrombopag. As compared with a historical cohort of 183 ITP patients, matched on the calendar year of ITP diagnosis with a 5:1 ratio, patients with multirefractory ITP were more likely to have secondary ITP (odds ratio OR, 4.84; 95% confidence interval CI, 1.31-17.86; P = .018) and monoclonal gammopathy of undetermined significance (OR, 5.94; 95% CI, 1.08-32.48; P = .04). The median duration of ITP before being recognized as multirefractory was 78 months (range, 6-450). The patients showed failure of a median of 10.5 prior treatment lines for ITP (range, 6-15). At the end of follow-up (median, 84 months; range, 12-455), only 1/14 patients achieved response with immunosuppressant therapy alone. By contrast, 7/10 patients achieved response with a combination of immunosuppressant therapy and thrombopoietin-receptor agonists that lasted for a median of 15 months (range, 6-32). Throughout the course of ITP, 5/37 patients died, 3 with ITP (bleeding, n = 2; sepsis n = 1); 15 (40%) had at least 1 bacterial infection and 9 (24%) at least 1 episode of thrombosis. In conclusion, multirefractory ITP was associated with high morbidity and mortality. Combining an immunosuppressant therapy with thrombopoietin-receptor agonists may be a good strategy for management for these patients with severe disease.
•The baseline characteristics of multirefractory ITP differed from “typical” ITP, outcome was severe, and was associated with high morbidity and mortality.•Combining immunosuppressant therapy with a thrombopoietin-receptor agonist may be a relevant option for these patients.
Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration (HCQ) varies widely between patients and is a marker and predictor of SLE ...flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target HCQ ≥1000 ng/ml to reduce SLE flares.
HCQ was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with HCQ from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target HCQ (group 2). The primary end point was the number of patients with flares during 7 months of follow-up.
Overall, mean HCQ was 918±451 ng/ml. Active SLE was less prevalent in patients with higher HCQ. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in HCQ in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low HCQ (20.5% vs 35.1%, p=0.12).
Although low HCQ is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.
Background
Neurological complications of systemic lupus erythematosus (SLE) are wide and may rarely involve the peripheral nervous system. However, no case of meningoradiculitis has been ...well-detailed.
Methods
We report a patient with lupus-associated meningoradiculitis.
Results
A 57-year-old woman had SLE without neurological involvement, treated with hydroxychloroquine, methotrexate, and prednisone for 10 years. Six months after the drug discontinuation for SLE, she acutely developed gait instability, paresthesia, and neuropathic pain of the four limbs. The neurological examination and nerve conduction studies were consistent with radiculopathies. Cerebrospinal fluid (CSF) analysis showed lymphocytic meningitis. The spinal magnetic resonance imaging (MRI) revealed thickening and an enhancement of the lumbosacral roots consistent with meningoradiculitis. The extensive investigations did not argue for a differential diagnosis of SLE. The patient dramatically improved upon corticosteroids. At the last follow-up, the patient still reported mild paresthesia but the clinical examination, the CSF, and the spinal MRI were normal.
Conclusion
This well-detailed case of meningoradiculitis broadens the spectrum of neurological complications in SLE. Early recognition of such complications might lead to efficient immunotherapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
B-cell activating factor may be involved in the failure of B-cell depleting therapy with rituximab in immune thrombocytopenia (ITP) by promoting the emergence of splenic long-lived plasma cells. From ...results obtained in mouse models, we hypothesized that combining rituximab with sequential injections of belimumab could increase the rate of response at one year in patients with persistent or chronic ITP by preventing the emergence of these long-lived plasma cells. The study was a single-center, single arm, prospective phase 2b trial (RITUX-PLUS, NCT03154385) investigating the safety and efficacy of rituximab given at a fixed dose of 1,000 mg, two weeks apart, combined with five infusions of belimumab, 10 mg/kg at week 0 (W0)+2 days, W2+2 days, W4, W8 and W12 for adults with primary persistent or chronic ITP. The primary endpoint was the total number of patients achieving an overall response (complete response + response) at W52 according to a standard definition. In total, 15 non-splenectomized adults, nine (60%) with persistent IPT and six (40%) with chronic ITP, were included. No severe adverse event, infection, or severe hypogammaglobulinemia was observed. Thirteen patients achieved an initial overall response. At W52, 12 (80%) patients achieved an overall response, including ten (66.7%) with complete response. When compared with a cohort of patients receiving rituximab alone, the kinetics of B-cell repopulation appeared similar, but the number of circulating T follicular helper cells was significantly decreased with belimumab combination therapy. Combining rituximab and belimumab seems a promising strategy in ITP, with high efficacy and acceptable safety.
Aseptic abscess (AA) syndrome is a rare type of inflammatory disorder involving polymorphonuclear neutrophils (PMNs), often associated with inflammatory bowel disease (IBD). This study sought to ...describe the clinical characteristics and evolution of this syndrome in a large cohort. We included all patients included in the French AA syndrome register from 1999 to 2020. All patients fulfilled the criteria outlined by André et al. in 2007. Seventy-one patients were included, 37 of which were men (52.1%), of a mean age of 34.5 ± 17 years. The abscesses were located in the spleen (71.8%), lymph nodes (50.7%), skin (29.5%), liver (28.1%), lung (22.5), and rarer locations (brain, genitals, kidneys, ENT, muscles, or breasts). Of all the patients, 59% presented with an associated disease, primarily IBD (42%). They were treated with colchicine (28.1%), corticosteroids (85.9%), immunosuppressants (61.9%), and biologics (32.3%). A relapse was observed in 62% of cases, mostly in the same organ. Upon multivariate analysis, factors associated with the risk of relapse were: prescription of colchicine (HR 0.52; 95% CI 0.28–0.97; p = 0.042), associated IBD (HR 0.57; 95% CI 0.32–0.99; p = 0.047), and hepatic or skin abscesses at diagnosis (HR 2.14; 95% CI 1.35–3.40; p = 0.001 and HR 1.78; 95% CI 1.07–2.93; p = 0.024, respectively). No deaths occurred related to this disease. This large retrospective cohort study with long follow up showed that AA syndrome is a relapsing systemic disease that can evolve on its own or be the precursor of an underlying disease, such as IBD. Of all the available treatments, colchicine appeared to be protective against relapse.
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