Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE: To describe the disease course of CLIPPERS. DESIGN: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING: Academic research. PATIENTS: Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES: The therapeutic management of CLIPPERS was evaluated. RESULTS: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.journal article2012 Julimporte

Humoral immune response to 13 valent-conjugate and 23-valent polysaccharide pneumococcal vaccines in RA patients treated with Abatacept: results of the open randomized controlled trial vacina (vaccination against pneumococcal in naïve Abatacept rheumatoid arthritis patients)

International audienceBackground: To prevent infections, EULAR recommends to vaccinate RA patients against streptococcal pneumoniae. It is recommended to vaccine with the conjugate vaccine (PCV13) followed by a dose of PPSV23 at least 8 weeks later. PCV13 is a T- cell dependent vaccine whereas PPSV23 induces a T-independent humoral response. Abatacept is a biological DMARD that inhibits T cell activation.Objectives: We hypothesized that the humoral response may be more affected under abatacept after PCV13 vaccination than after PPSV23. To adress this question, we compared the humoral response four weeks after vaccination with PCV13 or PPSV23 in RA patients treated with abatacept.Methods: We conducted a prospective, multicenter, randomized, open-label study in patients with RA according to ACR/EULAR 2010 criteria, and starting abatacept because of inadequate response to MTX or leflunomide (DAS28>3,2). Patients were randomized in 2 groups: the first group (G1) was vaccinated with the PPSV23 and the second group (G2) with PCV13 and PPSV23 8 weeks later. Abatacept was to be started on the same day as the first vaccine (PCV13 or PPSV23). Patients having been treated previously with rituximab within the last year were excluded. A patient was considered as responder if there was a two-fold increase in the antibodies titer measured by ELISA for at least 3 of 5 serotypes of interest (1, 3, 14, 7F, 19A) which are the most frequently involved in pneumococcal infections. For the primary endpoint, we compared the rate of responders at one month in G1 and G2 using a Chi-Square test. Sample size calculation based on alpha risk 5% and 80% power requirements resulted in 80 patients. Tolerance of the vaccines were collected within the first week and later in a patient booklet. Adverse events were also collected at 1, 2, 6 and 12 months.Results: Eighty patients were included and randomized in the two groups: 40 in G1 and 40 in G2 (1 patient withdrew his consent before any treatment in G2). Characteristics of patients are described in Table 1. Female were more represented in G1 (82.5%) compared to G2 (64.1%). Lymphocyte count were significantly higher in G1 compared to G2: 1841/uL (+/-887) vs 1603/uL (+/-580). In the mITT, the rate of responders was 47.5% in in G1 and 38.46% in G2 (p=0.42) with a RR of 1.23 (IC95%: 0.73-2,06; when comparing responders in PPSV23 vs PCV13 groups. This absence of difference was confirmed with a per protocol analysis (p=1) and after adjusting for gender and lymphocytes count with a logistic regression test (RR=1.6 IC95% 0.6-4.2). 17 infections were reported in G1 and 28 in G2 with 3 severe infections but no pneumococcal infection.Conclusion: In RA patients treated with abatacept combined with sDMARDs (MTX or LEF), the rate of responders is similar 28 days following vaccination with PCV13 or PPSV23. Although PCV13 is a T cell dependent vaccine, immu- nogenicity to PCV13 under abatacept is similar to PPSV23. There were no unexpected side effects after pneumococcal vaccines

Comparison of clinical safety between standard versus extended interval dosing of immune checkpoint inhibitors: a real-world retrospective cohort study

International audienceExtended interval dosing (ED) for inhibitors of programmed cell death protein 1 (anti-PD-1) (nivolumab, pembrolizumab) or its ligand (anti-PD-L1) (durvalumab) were recently approved based on pharmacokinetic model results that predicted a benefiterisk profile comparable with the standard dosing (SD) regimen. However, safety data in real-world condition of use are lacking. The objective was to compare the incidence and the risk factors of serious immune-related adverse events (irAEs) and any-grade irAEs between the SD and ED regimens in patients treated with anti-PD-1 or anti-PD-L1. Materials and methods: IrAEs were assessed from medical records in all new users of nivolumab, pembrolizumab, or durvalumab between 1 January 2019 and 31 December 2020 across two oncology centers in France. The incidence of irAEs was compared between both dosing regimens using Cox proportional hazards models adjusting for the main available confounders. Results: Among 686 patients included, 63% were new users of an SD regimen, 14% of ED regimen, and 23% started with SD and switched to ED regimen during follow-up. Overall, 34.6% of patients experienced at least one irAE of any grade and 11.4% presented at least one serious grade !3 irAE. No statistical difference was found between the SD and ED regimen on the risk of grade !3 irAEs [adjusted hazard ratio (HR) 1.40, 95% confidence interval (CI) 0.71-2.76] but our results suggest an increased risk of any-grade irAEs with the ED regimen (adjusted HR 1.46, 95% CI 1.00-2.12, P ¼ 0.048). IrAEs resolved without sequelae in 46.4% of cases, and they were fatal for three patients (0.4%). Autoimmune pre-existing condition was confirmed as a risk factor for grade !3 irAEs (HR 2.56, 95% CI 1.53-4.27) and for all-grade irAEs (HR 1.60, 95% CI 1.17-2.20). Conclusions: In a real-world setting, according to the regimen chosen by the oncologist based on clinical characteristics, we did not observe an increase in grade !3 irAE incidence between the SD and ED regimens

Interruption of outpatient follow-up in physical and rehabilitation medicine: Observational cross-sectional study of deleterious consequences of the first COVID-19 lockdown in France

International audienc

A regional strategy to decrease the time to thrombectomy in patients with low probability of treatment by thrombolysis

International audienceBackground and purpose: The best transportation strategy for patients with suspected large vessel occlusion (LVO) is unknown. Here, we evaluated a new regional strategy of direct transportation to a Comprehensive Stroke Center (CSC) for patients with suspected LVO and low probability of receiving intravenous thrombolysis (IVT) at the nearest Primary Stroke Center (PSC).Methods: Patients could be directly transported to the CSC (bypass group) if they met our pre-hospital bypass criteria: high LVO probability (i.e., severe hemiplegia) with low IVT probability (contraindications) and/or travel time difference between CSC and PSC<15 minutes. The other patients were transported to the PSC according to a "drip-and-ship" strategy. Treatment time metrics were compared in patients with pre-hospital bypass criteria and confirmed LVO in the bypass and drip-and-ship groups.Results: In the bypass group (n=79), 54/79 (68.3%) patients met the bypass criteria and 29 (36.7%) had confirmed LVO. The positive predictive value of the hemiplegia criterion for LVO detection was 0.49. In the drip-and-ship group (n=457), 92/457 (20.1%) patients with confirmed LVO met our bypass criteria. Among the 121 patients with bypass criteria and confirmed LVO, direct routing decreased the time between symptom discovery and groin puncture by 55 minutes compared with the drip-and-ship strategy (325 vs. 229 minutes, P<0.001), without significantly increasing the time to IVT (P=0.19).Conclusions: Our regional strategy led to the correct identification of LVO and a significant decrease of the time to mechanical thrombectomy, without increasing the time to IVT, and could be easily implemented in other territories

Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients

Taieb, Guillaume Duflos, Claire Renard, Dimitri Audoin, Bertrand Kaphan, Elsa Pelletier, Jean Limousin, Nadege Tranchant, Christine Kremer, Stephane de Seze, Jerome Lefaucheur, Romain Maltete, David Brassat, David Clanet, Michel Desbordes, Patrice Thouvenot, Eric Magy, Laurent Vincent, Thierry Faillie, Jean-Luc de Champfleur, Nicolas Castelnovo, Giovanni Eimer, Sandrine Branger, Dominique Figarella Uro-Coste, Emmanuelle Labauge, Pierre United States Archives of neurology Arch Neurol. 2012 Jul;69(7):847-55. doi: 10.1001/archneurol.2012.122.BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE: To describe the disease course of CLIPPERS. DESIGN: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING: Academic research. PATIENTS: Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES: The therapeutic management of CLIPPERS was evaluated. RESULTS: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, >/=5) and brainstem and spinal cord atrophy. CONCLUSIONS: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses