Abstract Circulating mixed cryoglobulins are detected in 40%–60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in about 15% of patients. ...Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct acting antiviral drugs in these patients. We performed open-label, prospective, multi-center study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas. Forty-one consecutive patients with active HCV-associated CryoVas (median age, 56 years; 53.6% women) were recruited from hospitals in Paris, France from 2014 through 2016. They received sofosbuvir (400 mg/day) plus daclatasvir (60 mg/day) for 12 weeks (n=32) or 24 weeks (n=9) and evaluated every 4 weeks until week 24 and at week 36. Blood samples were analyzed for complete blood count, serum chemistry profile, level of alanine aminotransferase, rheumatoid factor activity, C4 fraction of complement, and cryoglobulin; peripheral blood mononuclear cells were isolated for flow cytometry analysis. Thirty-seven patients (90.2%) had a complete clinical response (defined by improvement of all the affected organs involved at baseline and no clinical relapse) after a median time of 12 weeks’ therapy; all had a sustained virologic response (no detectable serum HCV RNA 12 weeks after the end of antiviral therapy). Patients’ mean cryoglobulin level decreased from 0.56±0.18 at baseline to 0.21±0.14 g/L at week 36, and no cryoglobulin was detected in 50% of patients at this time point. After antiviral therapy, patients had increased numbers of T-regulatory cells, IgM+CD21–/low memory B cells, CD4+CXCR5+ IL21+ cells, and T-helper 17 cells, compared with before therapy. After a median follow-up period of 26 months (interquartile range, 20–30 months), no patients had a serious adverse event or relapse of vasculitis.
Objective
Oral ulcers, the hallmark lesion of Behçet's disease (BD), can be disabling and resistant to conventional treatment, and there is a need for safe and effective treatment. We undertook this ...study to investigate the long‐term safety and efficacy of ustekinumab therapy for BD‐related oral ulcers that are resistant to colchicine.
Methods
This multicenter, prospective, open‐label study included 30 patients who fulfilled the criteria of the International Study Group for BD and who were diagnosed as having active oral ulcers resistant to colchicine. Patients were treated subcutaneously with ustekinumab 90 mg at inclusion, at week 4, and then once every 12 weeks. Each patient was assessed longitudinally for the presence and number of oral ulcers, and median numbers of oral ulcers (with interquartile range IQR) were calculated. The primary efficacy end point was the proportion of patients at week 12 who experienced complete response, defined as having no oral ulcers.
Results
The median number of oral ulcers per patient during ustekinumab therapy was significantly lower at week 12 compared to baseline (0 IQR 0–1 versus 2 IQR 2–3; P < 0.0001). Complete response was achieved in 60.0% and 88.9% of patients at weeks 12 and 24, respectively. The median Behçet's Syndrome Activity Score (in which higher scores indicate more active disease) was significantly lower at weeks 12 and 24 (17.5 IQR 10–42.5 and 10 IQR 8–11, respectively) versus baseline (70 IQR 50–70; P < 0.0001). After a median follow‐up of 12 months (IQR 6–16 months), 26 patients (86.7%) were still receiving ustekinumab treatment. Reasons for ustekinumab discontinuation included BD flare (n = 3) and side effects (n = 1). Seven patients (23.3%) experienced adverse events, including headaches (n = 4) and asthenia (n = 2), with no serious side effects.
Conclusion
Ustekinumab seems to be effective in treating BD‐related oral ulcers that are resistant to treatment with colchicine.
Abstract Objective To evaluate the efficacy and safety of ustekinumab in the treatment of oral ulcers (OU) in patients with Behçet's disease (BD). Patients and methods Prospective study including 14 ...patients median age of 39 (34; 41) years, with 71% of men fulfilling criteria of the International Study Group for BD and with active OU resistant to colchicine. Patients received ustekinumab 90 mg (n = 11) or 45 mg (n = 3) subcutaneously at inclusion, at week 4, and every 12 weeks. The primary efficacy endpoint was the proportion of patients with complete response (CR), defined as no oral ulcer, at week 12. Results At week 12, 64% were in CR, 21% in partial response and 14% non-responders. The median number of OU decreased from 2 2; 4 to 1 0; 1.25 (p = 0.0005) at week 12. Mean change from baseline to week 12 of Behçet's syndrome activity score (BSAS) was 22.8 ± 0.3 (p = 0.01). The median daily corticosteroids dose decreased from 12.5 (10; 16.3) to 5 5; 10 mg/day (p = 0.02). Three patients reported headaches, leading to discontinuation of ustekinumab in one case. After a median follow-up of 7 3; 12 months, 10 (71%) patients were still receiving ustekinumab and four (28%) experienced a relapse. Decreased levels of circulating IL-17 and IL-12 median IQR; 3.9 1.6; 10.6 vs. 29.2 25.2; 42.7 pg/ml, and 29.4 23.1; 33.3 vs. 56.1 51.1; 64.4 pg/ml, p = 0.008 for both were observed under ustekinumab, respectively. Conclusion Ustekinumab seems to be efficient and safe for patient with BD and refractory OU although relapses are frequent.
Temporal arteritis in IgG4 related disease Ferfar, Yasmina; Charlotte, Frédéric; Cacoub, Patrice ...
Joint, bone, spine : revue du rhumatisme,
03/2021, Volume:
88, Issue:
2
Journal Article
Peer reviewed
•We report the first observation of a temporal artery aneurysm revealing IgG4 related disease.•There are many vascular disorders in IgG4 related disease.•IgG4 related disease has been listed as an ...etiology of large vessel vasculitis in the revised Chapel Hill consensus conference nomenclature of vasculitides.
In small-size and short-term studies of hepatitis C virus-associated cryoglobulinemia vasculitis (HCV-CryoVas), patients had a higher rate of response and tolerance to direct-acting antiviral (DAA) ...agents than interferon-containing regimens. We collected follow-up data from a clinical trial to determine the long-term effectiveness and tolerance of all-oral, interferon-free DAA regimens in patients with CryoVas.
We collected follow-up data from a prospective international multicenter cohort study of 148 patients with symptomatic HCV-CryoVas (53.7% with cirrhosis and 49.3% naive to treatment with DAAs). All patients received DAA (sofosbuvir plus daclatasvir, n = 53; sofosbuvir plus ribavirin, n = 51; sofosbuvir plus ledipasvir, n = 23; or sofosbuvir plus simeprevir, n = 18), for 12 or 24 weeks, from 2014 through 2017; the median follow-up time was 15.3 months. A complete clinical response was defined as improvement of all organs involved at baseline and the absence of clinical relapse; a partial response was defined as improvement in some but not all organs involved at baseline. The primary end point was clinical response of CryoVas symptoms at week 12 after stopping DAA therapy.
A complete response was reported for 106 patients (72.6%), a partial response for 33 patients (22.6%), and no response for 7 patients (4.8%). Cryoglobulins were no longer detected in blood samples from 53.1% of patients, and 97.2% of the patients had a sustained virologic response to therapy. Premature DAA withdrawal was reported for 4.1% of patients. Factors associated with no or partial response to therapy included a severe form of CryoVas (odds ratio, 0.33; 95% CI, 0.12-0.91; P = .03) and peripheral neuropathy (odds ratio, 0.31; 95% CI, 0.11-0.84; P = .02). After a median follow-up time of 15.3 months, 4 patients (2.8%) died. The CryoVas manifestation of purpura was cleared from 97.2% of patients, renal involvement from 91.5% of patients, arthralgia from 85.7% of patients, neuropathy from 77.1% of patients, and cryoglobulinemia from 52.2%.
In a long-term follow-up analysis of data from a clinical trial, we found that more than 95% of patients with HCV-CryoVas have a full or partial response of symptoms to different DAA treatment regimens. Fewer than 5% of patients stop therapy prematurely and less than 3% die. A severe form of CryoVas and peripheral neuropathy were associated with a lack of response of HCV-CryoVas to DAA therapy.
Arterial involvement in Behçet disease (BD) is rare, and its surgical management is a major concern because of its high recurrence rate. This study evaluated the influence of the surgical technique, ...device, and immunosuppressive treatment used on the postoperative recurrence in patients with non-pulmonary arterial BD.
A single-center, retrospective study was conducted of 23 patients meeting the international criteria for BD who underwent surgery for arterial involvement between May 1996 and September 2015. Recurrence was defined as the occurrence of arterial aneurysm or thrombosis during follow-up. Perioperative medical treatment and surgical technique used were reported.
There were 47 surgical procedures performed in 23 patients. Mean follow-up was 8.4 ± 7.5 years. Initial arterial lesions were aneurysms and thrombosis in 85% and 15% of cases, respectively. Arterial lesions were aortic and peripheral in 48% and 52% of cases. Recurrence rate was 51%. Recurrences developed within <1 year in 24% of cases and at the same anatomic site in 92% of cases. Among the 24 recurrences, 17 were false aneurysms, 6 were thrombosis, and 1 was a true aneurysm in a different arterial site. To treat the arterial lesion, direct anastomosis was performed in 6 cases; bypass using the saphenous vein, graft, or allograft was performed in 6, 27, and 5 cases, respectively; and stent graft was used in 3 cases. Vascular lesions involved the aorta in 19 cases and a peripheral artery in 28 cases.
Preoperative medical treatments, including colchicine, steroids, and immunosuppressants, significantly decreased recurrence rate: 28% (7/25) vs 75% (15/20) in untreated patients (P = .002). The recurrence rate was 42.5% (17/40) in patients treated postoperatively vs 80% (4/5) in untreated patients. The nature of the device used (vein, prosthetic graft, allograft, stent graft, or direct anastomosis) did not change the risk of recurrence. When anastomoses were protected using the prosthetic sleeving technique, the recurrence rate was three times lower (P = .08).
Relapse is a main concern after surgical repair of arterial BD. This study suggests the need for targeted perioperative medical management to reduce the risk of arterial recurrence in BD patients. To this end, a multidisciplinary approach is mandatory. The use of sleeve anastomosis is associated with a numerically lower risk of recurrence. However, further studies are needed to confirm this efficacy.
To report the long term mortality in Takayasu arteritis (TA) and to identify prognosis factors.
We analyzed the causes of death and the factors associated with mortality in a cohort of 318 patients ...median age at diagnosis was 36 25–47 years and 276 (86%) patients were women fulfilling American College of Rheumatology and/or Ishikawa criteria of TA. A prognostic score for death and vascular complications was elaborated based on a multivariate model.
Among 318 TA patients, 16 (5%) died after a median IQR follow-up of 6.1 2.8–13.0 years. The median age at death was 38 25–47 years with 88% of women. Main causes of death included mesenteric ischemia (n = 4, 25%) and aortic aneurysm rupture (n = 4, 25%). The mortality rate at 5 and 10 years was of 1.9% and 3.9%, respectively. Caucasians (p = 0.049) and smokers (p = 0.002) TA patients were more likely to die. There was an increased mortality in TA (SMR with 95% confidence interval, 2.73 1.69–4.22) as compared to age and sex matched healthy controls. We defined high risk patients for death and vascular complications according to the presence of two of the following factors (i.e a progressive clinical course, thoracic aorta involvement and/or retinopathy). In the high risk TA group, the 5-year incidence of death and vascular complication was 48.5% compared to 21.6% (p = 0.001) in those with low risk.
The overall mortality in our Takayasu cohort was 5% after a median follow-up of 6.1 years. We identified specific characteristics that distinguish TA patients at highest risk for death and vascular complications.
•We report the long term mortality in a cohort of 318 patients with Takayasu arteritis.•We report an overall mortality of 5% after a median follow-up of 6.1 2.8–13.0 years.•Patients with TA had a standardized mortality ratio (SMR) of 2.7 CI 95% 1.69–4.22.•We developed a prognosis score that allow classifying patients as low or high risk to death or vascular complication.•The prognosis score is based on disease course pattern, thoracic aorta involvement, and retinopathy.
Prognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the ...management of COVID-19 patients hospitalized in a medical ward. This French single-center prospective cohort study evaluated 152 patients with positive severe acute respiratory syndrome coronavirus 2 real-time reverse transcriptase-polymerase chain reaction assay, hospitalized in the Internal Medicine and Clinical Immunology Department, at Pitié-Salpêtrière's Hospital, in Paris, France, a tertiary care university hospital. Predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death) were evaluated in multivariable logistic regression models; models' performances, including discrimination and calibration, were assessed (C-index, calibration curve, R2, Brier score). A validation was performed on an external sample of 132 patients hospitalized in a French hospital close to Paris, in Aulnay-sous-Bois, Île-de-France. The probability of ICU transfer or death was 32% (47/147) (95% CI 25-40). Older age (OR 2.61, 95% CI 0.96-7.10), poorer respiratory presentation (OR 4.04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1.76-9.25), higher CRP-level (OR 1.63 per 100mg/L increment, 95% CI 0.98-2.71) and lower lymphocytes count (OR 0.36 per 1000/mm3 increment, 95% CI 0.13-0.99) were associated with an increased risk of ICU requirement or death. A 9-point ordinal scale scoring system defined low (score 0-2), moderate (score 3-5), and high (score 6-8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14. Therefore, in this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, a simplified scoring system at admission predicted the outcome at D14.
•Première observation d’un anévrisme de l’artère temporale révélant une maladie liée aux IgG4.•Il existe de nombreuses atteintes vasculaires dans les maladies liées aux IgG4.•La maladie liée aux ...IgG4 a été répertoriée comme cause de vascularite des gros vaisseaux dans la nomenclature révisée des vascularites de la conférence de consensus de Chapel Hill.
PDF
