Efficacy of tacrolimus as long-term immunotherapy for neuronal surface antibody-mediated autoimmune encephalitis

Aims: We aimed to verify the efficacy and safety of tacrolimus as long-term immunotherapy for the treatment of neuronal surface antibody-mediated autoimmune encephalitis (AE) during the first attack. Methods: In this retrospective observational cohort study, patients with neuronal surface antibody-mediated AE who experienced the first attack were enrolled. We compared the outcomes of 17 patients who received tacrolimus with those of 47 patients treated without tacrolimus. Patients were assessed at onset and 3, 6, and 12 months, as well as at the last follow-up, by using the modified Rankin scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The efficacy of tacrolimus was also compared in a subgroup of patients with anti-NMDA receptor encephalitis. Results: Among all patients with neuronal surface antibody-mediated AE, those receiving tacrolimus had lower median mRS scores [1 (IQR = 0–1) versus 2 (IQR = 1–3) in controls, p = 0.001)], CASE scores [2 (IQR = 1–3) versus 3 (IQR = 2–7), p = 0.006], and more favorable mRS scores (94.1% versus 68.1%, p = 0.03) at the 3-month follow-up. No difference was found at the last follow-up. There was no significant difference in the occurrence of relapse and adverse events between the two groups (11.8% versus 14.9%, p = 0.75). In the subgroup of patients with anti-NMDA receptor encephalitis, patients treated with tacrolimus had a lower median mRS score at the 3-month follow-up [1 (IQR = 0–2) versus 2 (IQR = 1–3), p = 0.03]; however, no difference in the outcome was detected at the last follow-up. Conclusion: Tacrolimus can be used as long-term immunotherapy in patients with neuronal surface antibody-mediated AE during the first attack. Treatment with tacrolimus appears to accelerate the clinical improvement of neuronal surface antibody-mediated AE.

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Permacol Collagen Paste Injection for Treatment of Complex Cryptoglandular Anal Fistulas: An Observational Cohort Study With a 2-Year Follow-up

Surgical Innovation ◽

10.1177/1553350618808120 ◽

2018 ◽

Vol 26 (2) ◽

pp. 168-179 ◽

Cited By ~ 3

Author(s):

Michele Schiano di Visconte ◽

Andrea Braini ◽

Luana Moras ◽

Luigi Brusciano ◽

Ludovico Docimo ◽

...

Keyword(s):

Anal Fistulas ◽

Recurrent Fistula ◽

Pain Scores ◽

Significant Difference ◽

Paste Extrusion ◽

Observational Cohort ◽

Grading Scale

Background. Permacol paste injection is a novel treatment approach for complex cryptoglandular anal fistulas. This study was performed to evaluate the long-term clinical outcomes of treatment with Permacol paste for complex cryptoglandular fistulas. Methods. Patients with primary or recurrent complex cryptoglandular anal fistulas treated with Permacol paste from 2014 to 2016 were retrospectively analyzed. Results. A total of 46 patients (median age, 41.3 years; 21 female) underwent Permacol paste injection; 20 patients (43%) had previously undergone failed fistula surgery. The patients had experienced anal fistula-related symptoms for a median of 10 weeks (range, 3-50 weeks). All patients had a draining seton in situ for a median of 10 weeks (range, 4-46 weeks). The median follow-up time was 24 months (range, 1-25 months). At the 1-month follow-up, 2 patients had paste extrusion and 2 had anal abscesses. The mean preoperative Continence Grading Scale score was 1.10 ± 1.40, and that at 3 months postoperatively was 1.13 ± 1.39 ( P = .322). There was a significant difference in the preoperative and the 1- and 3-month postoperative pain scores ( P < .001). At the 24-month follow-up, the healing rate was 50% (n = 23). A total of 19 patients (41%) with a recurrent fistula after failed Permacol paste injection required additional operative procedures. The satisfaction rate at the 2-year follow-up was 65%. Conclusion. Permacol paste injection is minimally invasive and technically easy to perform. It can be considered as a viable and reasonable option for the treatment of complex cryptoglandular anal fistulas in patients with fecal continence disorders.

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RARE-36. BORTEZOMIB WOKE UP A PATIENT WITH ANTI-NMDA RECEPTOR ENCEPHALITIS REFRACTORY TO STANDARD THERAPY AND LONG TERM FOLLOW-UP

Neuro-Oncology ◽

10.1093/neuonc/noz175.959 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi229-vi229

Author(s):

Kong Xiao-Tang ◽

Leonid Groysman ◽

Cyrus Dastur ◽

Beverly Fu ◽

Daniela Bota

Keyword(s):

Nmda Receptor ◽

Standard Therapy ◽

Autoimmune Encephalitis ◽

Ivig Therapy ◽

Term Care ◽

Good Communication ◽

Nmda Receptor Encephalitis ◽

Long Term Follow Up ◽

One Year

Abstract OBJECTIVE To report a case with refractory NMDA encephalitis in comatose for 18 months, who was treated successfully with bortezomib. BACKGROUND Anti-NMDA encephalitis is a rare autoimmune encephalitis. Standard therapy include corticosteroid, IVIG or plasma exchange, cyclophosphamide, rituximab, and tumor removal. Refractory cases are very severe and often stay in ICU on ventilation for several months to years. Bortezomib for the treatment of refractory anti-NMDA receptor encephalitis was reported. We have applied the treatment to our refractory case and successfully woke up the patient. And we have followed up the patient for 3 years. METHODS Case report. RESULTS A 40 yo male was diagnosed as anti-NMDA encephalitis. Standard therapy was applied. After stabilization, the patient was eventually discharged to ICU at a long term care subacute hospital. The patient was brought back for more Rituxan or steroid or IVIG therapy. The condition had not improved at all. Eighteen months in comatose, the patient had worsening NMDA titer in CSF to 1:640. Decision was made to start bortezumib as reported with modification: 1.3 mg/m2 bortezomib were administered on days 1, 8, 11 and 14 and allowed two weeks off therapy. After first cycle, the patent started to talk first word “hurt.” After 6 cycles, the patient sat up and started riding bicycles for physical therapy. The NMDA titer in CSF was reduced to 1:40 at the end of 6 cycles. One year later, the patent stood up and ambulated with a walker. One and half year later, the patient walks without assistance and his speech and cognition have significantly improved with good communication with family members and staff. CONCLUSIONS Proteasome inhibitor bortezomib might be considered to be the third line therapy as early as possible if the first line and second line are ineffective to treat anti-NMDA receptor encephalitis.

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OP0270 LONG-TERM EFFICACY AND SAFETY OF BOSENTAN IN PATIENTS WITH DIGITAL ULCERS RELATED TO SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1916 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 164-164

Author(s):

N. Cristina ◽

L. Groseanu ◽

F. Berghea ◽

A. Balanescu ◽

V. Bojinca ◽

...

Keyword(s):

Systemic Sclerosis ◽

Control Group ◽

Digital Ulcers ◽

Efficacy And Safety ◽

Term Efficacy ◽

Elevated Liver Enzymes ◽

Significant Difference ◽

The Mean

Background:Two pivotal studies, RAPIDS-1 and RAPIDS-2 revealed that bosentan reduces the development of new digital ulcers (DUs) in patients with systemic sclerosis (SSc). However data regarding the long-term use of this dual endothelin antagonist receptor in the treatment of DUs is scarce.Objectives:The aim of the present study was to evaluate long term efficacy and safety profile of bosentan in patients with DUs related to SSc.Methods:A prospective observational case-control study, conducted between 2014 and 2020 enrolled 65 SSc patients with ≥1 active DUs at baseline, who received bosentan therapy. Demographic and clinical features, including DUs incidence and patients subjective perception of DU pain and/or Raynaud’s Phenomenon, were collected. Nailfold videocapillaroscopy was performed in all patients.Results:The study included 51 females and 14 males, with a mean age of 52.6 years, 30 with diffuse subset, most of them with late scleroderma pattern (46/65). Number of DUs at baseline was 4.55 (±2.8), median duration of treatment was 25.95 (±19.4) months. Microangiopathy evolution score (MES) was 5.1 (2.19), visual analog scale (VAS) for DU was 77.9, VAS for Raynaud was 73.4.Patients receiving bosentan had clinically significant reduction in the mean number of DU (p<0.001). The effect was most powerful for the first 6 months of treatment, but the improvement was sustained until 24 months’ follow-up, when the mean DU number reached a plateau that was kept until end of study. 6 month and 24 month evaluations also revealed significant decrease in the VAS for DU (p<0.05) and in the VAS for Raynaud (p<0.01). Statistically significant difference was noted between bosentan-treated and the control group with respect to the decrease in the mean number of digital ulcers. (p=0.005).There was a clear trend towards an improvement in MES score, between baseline and the next follow-up assessments (p=0.003). The difference was statistically significant when compared to control group, but only for the first 18 months of treatment (p<0.001).14 patients (28.75%) discontinued bosentan therapy for administrative reasons. The median time among patients who interrupted the treatment was 6.9 months. An accelerated development of new DU was described 6 months after (p=0.02). Following recommencement of bosentan, the mean number of DU has rapidly decreased (p=0.008). There was no significant difference between patients who temporarily discontinued bosentan for 6 or 12 months.Bosentan was stopped due to lack of efficacy in 2 cases and due to side effects in 7 cases: 4 elevated liver enzymes, 1 severe trombocytopenia, 1 dyspneea agravation and low blood pressure.Conclusion:The present data suggest that treatment with endothelin receptor antagonist bosentan was associated with a significant reduction in the mean number of DU in patients with SSc. The beneficial effect of bosentan persisted throughout the study but was most evident in the first 6 months of treatment. Statistical analysis showed a significant improvement of the microangiopathy evolution score from baseline to end of therapy. 14 patients had a high relapse rate due to potential rebound effect, 6 months after bosentan withdrawal.The drug was reintroduced succesfully for 10 (70%) patients with a significant decrease in the number of DU.References:[1]UK Scleroderma Study Group: digital vasculopathy in systemic sclerosis, Rheumatology, Volume 54, Issue 11, November 2015, Pages 2015[2]Groseanu L, Berghea F, Bojinca V, et al AB0779 Long term follow-up of a systemic sclerosis group treated with bosentan, Annals of the Rheumatic Diseases 2018;77:1523-1524.Disclosure of Interests:None declared

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A follow-up study of a randomized controlled study evaluating safety and efficacy of leuprorelin acetate every-3-month depot for 2 versus 3 or more years with tamoxifen for 5 years as adjuvant treatment in premenopausal patients with endocrine-responsive breast cancer

Breast Cancer ◽

10.1007/s12282-020-01205-w ◽

2021 ◽

Vol 28 (3) ◽

pp. 684-697

Author(s):

Junichi Kurebayashi ◽

Eiichi Shiba ◽

Tatsuya Toyama ◽

Hiroshi Matsumoto ◽

Minoru Okazaki ◽

...

Keyword(s):

Breast Cancer ◽

Disease Free Survival ◽

Controlled Study ◽

Efficacy And Safety ◽

Observation Study ◽

Randomized Controlled ◽

Significant Difference ◽

Premenopausal Patients

Abstract Background Previously, we conducted the 5-year open-label, randomized controlled trial (RCT) of leuprorelin adjuvant therapy in post-operative premenopausal patients with endocrine-responsive breast cancer, which was a pilot study to investigate the optimal duration of leuprorelin treatment. Since, however, long-term outcomes became required for the adjuvant endocrine therapy, we performed this follow-up observation study. Methods Follow-up observation study was performed up to 10th year after randomization, continuing RCT to evaluate the efficacy and safety of leuprorelin every 3 months for ≥ 3 versus 2 years, with daily tamoxifen for 5 years. Primary endpoints were disease-free survival (DFS) and 2-year landmark DFS. Results Eligible patients (N = 222) were randomly assigned to receive leuprorelin for either 2 years (N = 112) or ≥ 3 years (N = 110) with tamoxifen. Leuprorelin treatment for ≥ 3 years versus 2 years provided no significant difference in DFS (HR 0.944, 95% CI 0.486–1.8392) or 2-year landmark DFS (N = 99 and 102 in 2-year and ≥ 3-year groups, HR 0.834, 0.397–1.753). In small, higher-risk subgroup (n = 17); however, 2-year landmark DFS in ≥ 3-year group was significantly longer (HR 0.095, 0.011–0.850) than that in 2-year group. The incidence of bone-related adverse events was around 5% in both groups. Conclusions Adjuvant leuprorelin treatment for ≥ 3 years with tamoxifen only showed similar efficacy and safety profiles to those for 2 years in analyses among all patients but suggested greater benefit in higher-risk patients. No new safety signal was identified for long-term leuprorelin treatment. Trial registration number Not applicable. This was an observational study.

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Long-term Clinical Outcomes of Implantable Collamer Lens

Journal of the Korean Ophthalmological Society ◽

10.3341/jkos.2021.62.8.1043 ◽

2021 ◽

Vol 62 (8) ◽

pp. 1043-1052

Author(s):

Bu Ki Kim ◽

Young Taek Chung

Keyword(s):

Endothelial Cell ◽

Retinal Detachment ◽

Clinical Outcomes ◽

Cell Loss ◽

Efficacy And Safety ◽

Implantable Collamer Lens ◽

Significant Difference ◽

The Mean

Purpose: To evaluate the long-term clinical outcomes of implantable collamer lens (ICL) implantation in myopic patients.Methods: This retrospective study included 129 eyes of 68 patients who underwent ICL implantation for correction of myopia with a 10-year follow-up.Results: Ten years after ICL implantation, the mean uncorrected and corrected distance visual acuities (LogMAR) were 0.03 ± 0.13 and -0.07 ± 0.06, respectively. Ten years postoperatively, 52.7% and 84.5% of the eyes were within ± 0.5 and ± 1.0 diopters, respectively. The mean efficacy and safety indices were 0.91 ± 0.22 and 1.07 ± 0.19, respectively. There was no significant difference between mean preoperative (13.52 ± 2.88 mmHg) and postoperative (13.59 ± 3.55 mmHg) intraocular pressures. The endothelial cell density decreased from before surgery to 10 years after surgery (3,074 ± 365 cells/mm2, 2,812 ± 406 cells/mm2, respectively; mean decrease: 8.5 ± 10.8%; p = 0.011). Eight eyes (6.2%) developed cataract during follow-up, which was symptomatic in three eyes (2.3%) and treated with ICL explantation and phacoemulsification. Rhegmatogenous retinal detachment occurred in one eye (0.8%) and was treated with vitrectomy.Conclusions: ICL implantation for the correction of myopia had good efficacy and safety outcomes during long-term follow-up of 10 years. However, patients should be closely monitored for complications such as cataract formation, endothelial cell loss, and retinal detachment.

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Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study

The Lancet Neurology ◽

10.1016/s1474-4422(12)70310-1 ◽

2013 ◽

Vol 12 (2) ◽

pp. 157-165 ◽

Cited By ~ 1237

Author(s):

Maarten J Titulaer ◽

Lindsey McCracken ◽

Iñigo Gabilondo ◽

Thaís Armangué ◽

Carol Glaser ◽

...

Keyword(s):

Cohort Study ◽

Prognostic Factors ◽

Nmda Receptor ◽

Observational Cohort Study ◽

Term Outcome ◽

Long Term Outcome ◽

Nmda Receptor Encephalitis ◽

Observational Cohort

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Case Report: Daratumumab in a Patient With Severe Refractory Anti-NMDA Receptor Encephalitis

Frontiers in Neurology ◽

10.3389/fneur.2020.602102 ◽

2020 ◽

Vol 11 ◽

Author(s):

Dominica Ratuszny ◽

Thomas Skripuletz ◽

Florian Wegner ◽

Matthias Groß ◽

Christine Falk ◽

...

Keyword(s):

Nmda Receptor ◽

Neuropsychiatric Symptoms ◽

Clinical Status ◽

Disease Onset ◽

Autoimmune Encephalitis ◽

Intravenous Immunoglobulins ◽

Nmda Receptor Encephalitis ◽

Life Threatening ◽

Therapy Strategies

Anti-NMDA receptor encephalitis is the most common type of antibody mediated autoimmune encephalitis (AIE). Patients often develop neuropsychiatric symptoms and seizures, women are affected about four times more than men, and in about 50% the disease is associated with a neoplasia, especially teratomas of the ovary. We describe the case of a 20-year-old woman suffering from a severe therapy refractory course of anti-NMDA receptor encephalitis. Treatment included glucocorticoids, plasma exchange, intravenous immunoglobulins, rituximab, and bortezomib without clinical improvement. Due to a therapy refractive course 28 weeks after disease onset, the patient received 10 cycles of daratumumab. Therapy escalation was performed with the anti-CD38 monoclonal antibody daratumumab as off label treatment, based on the therapy of refractory myeloma and led to an improvement of her clinical status. She spent about 200 days on the intensive care unit, followed by several weeks on the intermediate care unit with close follow ups every 4–6 weeks afterward. During follow-up, the patient was able to resume everyday and self-care activities, reflected by the modified Rankin scale (mRS) and Barthel index. Because this disease is potentially life threatening and can lead to irreversible brain atrophy, development of further therapy strategies are of great importance. Our case describes a successful treatment for therapy refractory anti-NMDA receptor encephalitis using the anti-CD38 antibody daratumumab.

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Effect of rituximab or tumour necrosis factor inhibitors on lung infection and survival in rheumatoid arthritis-associated bronchiectasis

Rheumatology ◽

10.1093/rheumatology/kez676 ◽

2020 ◽

Vol 59 (10) ◽

pp. 2838-2846 ◽

Cited By ~ 1

Author(s):

Md Yuzaiful Md Yusof ◽

Kundan Iqbal ◽

Michael Darby ◽

Giovanni Lettieri ◽

Edward M Vital ◽

...

Keyword(s):

Therapeutic Choice ◽

Antitrypsin Deficiency ◽

Long Term Follow Up ◽

Alpha 1 Antitrypsin Deficiency ◽

Observational Cohort ◽

Alpha 1 Antitrypsin ◽

Retrospective Observational Cohort Study ◽

Necrosis Factor

Abstract Objective To evaluate rituximab (RTX) in patients with RA-associated bronchiectasis (RA-BR) and compare 5-year respiratory survival between those treated with RTX and TNF inhibitors (TNFi). Methods A retrospective observational cohort study of RA-BR in RTX or TNFi-treated RA patients from two UK centres over 10 years. BR was assessed using number of infective exacerbation/year. Respiratory survival was measured from therapy initiation to discontinuation either due to lung exacerbation or lung-related deaths. Results Of 800 RTX-treated RA patients, 68 had RA-BR (prevalence 8.5%). Post-RTX, new BR was diagnosed in 3/735 patients (incidence 0.4%). At 12 months post-Cycle 1 RTX, 21/68 (31%) patients had fewer exacerbations than the year pre-RTX, 36/68 (53%) remained stable and 11/68 (16%) had increased exacerbations. The rates of exacerbation improved after Cycle 2 and stabilized up to 5 cycles. Of patients who received ≥2 RTX cycles (n = 60), increased exacerbations occurred in 7/60 (12%) and were associated with low IgG, aspergillosis and concurrent alpha-1-antitrypsin deficiency. Overall, 8/68 (11.8%) patients discontinued RTX while 15/46 (32.6%) discontinued TNFi due to respiratory causes. The adjusted 5-year respiratory survival was better in RTX-treated compared with TNFi-treated RA-BR patients; HR 0.40 (95% CI 0.17, 0.96); P =0.041. Conclusion The majority of RTX-treated RA-BR patients had stable/improved pulmonary symptoms in this long-term follow-up. In isolated cases, worsening of exacerbation had definable causes. Rates of discontinuation due to adverse lung outcomes were better for RTX than a matched TNFi cohort. RTX is an acceptable therapeutic choice for RA-BR if a biologic is needed.

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A206 EVOLUTION OF PEDIATRIC AUTOIMMUNE CHOLANGITIS AND PRIMARY SCLEROSING CHOLANGITIS INTO ADULTHOOD

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.204 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 234-236

Author(s):

P Willems ◽

J Hercun ◽

C Vincent ◽

F Alvarez

Keyword(s):

Primary Sclerosing Cholangitis ◽

Sclerosing Cholangitis ◽

Response To Treatment ◽

Similar Proportion ◽

Autoimmune Cholangitis ◽

Significant Difference ◽

One Year ◽

Liver Tests

Abstract Background The natural history of primary sclerosing cholangitis (PSC) in children seems to differ from PSC in adults. However, studies on this matter have been limited by short follow-up periods and inconsistent classification of patients with autoimmune cholangitis (AIC) (or overlap syndrome). Consequently, it remains unclear if long-term outcomes are affected by the clinical phenotype. Aims The aims of this is study are to describe the long-term evolution of PSC and AIC in a pediatric cohort with extension of follow-up into adulthood and to evaluate the influence of phenotype on clinical outcomes. Methods This is a retrospective study of patients with AIC or PSC followed at CHU-Sainte-Justine, a pediatric referral center in Montreal. All charts between January 1998 and December 2019 were reviewed. Patients were classified as either AIC (duct disease on cholangiography with histological features of autoimmune hepatitis) or PSC (large or small duct disease on cholangiography and/or histology). Extension of follow-up after the age of 18 was done for patients followed at the Centre hospitalier de l’Université de Montréal. Clinical features at diagnosis, response to treatment at one year and liver-related outcomes were compared. Results 40 patients (27 PSC and 13 AIC) were followed for a median time of 71 months (range 2 to 347), with 52.5% followed into adulthood. 70% (28/40) had associated inflammatory bowel disease (IBD) (78% PSC vs 54% AIC; p=0.15). A similar proportion of patients had biopsy-proven significant fibrosis at diagnosis (45% PSC vs 67% AIC; p=0.23). Baseline liver tests were similar in both groups. At diagnosis, all patients were treated with ursodeoxycholic acid. Significantly more patients with AIC (77% AIC vs 30 % PSC; p=0.005) were initially treated with immunosuppressive drugs, without a significant difference in the use of Anti-TNF agents (0% AIC vs 15% PSC; p= 0.12). At one year, 55% (15/27) of patients in the PSC group had normal liver tests versus only 15% (2/13) in the AIC group (p=0.02). During follow-up, more liver-related events (cholangitis, liver transplant and cirrhosis) were reported in the AIC group (HR=3.7 (95% CI: 1.4–10), p=0.01). Abnormal liver tests at one year were a strong predictor of liver-related events during follow-up (HR=8.9(95% CI: 1.2–67.4), p=0.03), while having IBD was not (HR=0.48 (95% CI: 0.15–1.5), p=0.22). 5 patients required liver transplantation with no difference between both groups (8% CAI vs 15% CSP; p=0.53). Conclusions Pediatric patients with AIC and PSC show, at onset, similar stage of liver disease with comparable clinical and biochemical characteristics. However, patients with AIC receive more often immunosuppressive therapy and treatment response is less frequent. AIC is associated with more liver-related events and abnormal liver tests at one year are predictor of bad outcomes. Funding Agencies None

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