Long-term efficacy of adding intravenous immunoglobulins as treatment of refractory dysphagia related to myositis: a retrospective analysis

Rheumatology ◽  
2020 ◽  
Author(s):  
Margherita Giannini ◽  
Maria Luisa Fiorella ◽  
Marilina Tampoia ◽  
Francesco Girolamo ◽  
Marco Fornaro ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Assessment Tool ◽  
Intravenous Immunoglobulins ◽  
High Dose ◽  
Treatment Schedule ◽  
Inflammatory Myopathies ◽  
Endoscopic Evaluation ◽  
Sparing Effect

Abstract Objective Dysphagia is a life-threating manifestation of idiopathic inflammatory myopathies (IIM). However, we lack a univocal protocol for its treatment. The aim of this retrospective analysis was to evaluate the effectiveness of a step-up strategy by adding a 1-day pulse of IVIGs to immunosuppressants in IIM patients with refractory dysphagia diagnosed by Eating Assessment Tool (EAT)-10 and fibreoptic endoscopic evaluation of swallowing (FEES). Methods Dysphagia was defined as a pharyngo-oesophageal disturbance associated with EAT-10 score ≥3 and at least one FEES abnormality among propulsion failure, solid or liquid stasis. Eighteen out of 154 IIM patients had FEES-confirmed dysphagia and underwent 1 day IVIG 2 g/kg repeated 1 month apart for 3 months, because of dysphagia refractory to high-dose glucocorticoids with methotrexate and/or azathioprine. Clinical characteristics along with myositis-specific antibodies and muscle histopathological findings were studied in FEES-dysphagia IIM and IIM control patients. Results After three monthly doses of IVIG, EAT-10 score dropped with complete recover of defective propulsion and progressive decrease in percentage of both solid and liquid stasis. At 52-weeks’ follow-up, reached in 12 patients, all these parameters were stable or further improved. An improvement in manual muscle strength test and a steroid-sparing effect of IVIG were also observed. Anti-PM/Scl 75/100 antibodies were much more frequent in the FEES-dysphagia group, while anti-Jo1 antibody was rarely detected. Conclusion Our treatment schedule with 2 g/kg IVIG was effective for IIM-associated refractory dysphagia assessed by the combination of EAT-10 and FEES. These findings need to be prospectively tested in a larger cohort of IIM patients.

Fludarabine and Mitoxantrone Followed by Yttrium-90 Ibritumumab Tiuxetan in Untreated Patients with Follicular Lymphoma. Long Term Efficacy and Toxicity Results of the FLUMIZ Trial.

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1604-1604
Author(s):  
Pier Luigi Zinzani ◽  
Enrico Derenzini ◽  
Cinzia Pellegrini ◽  
Luigi Rigacci ◽  
Alberto Fabbri ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Disease Progression ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Treatment Schedule ◽  
Combination Strategy ◽  
Term Efficacy ◽  
Yttrium 90

Abstract Abstract 1604 We previously reported the results of a multicenter non-randomized phase II trial of fludarabine and mitoxantrone plus radioimmunotherapy (RIT) [FLUMIZ (Fludarabine, Mitoxantrone, Zevalin) trial], demonstrating that this combination was safe and very effective in untreated patients with follicular non-Hodgkin lymphoma. We are now providing long term efficacy and toxicity results of this combination strategy. Sixty-one patients with stage III and IV untreated follicular lymphoma were enrolled between June 2004 and April 2006, at 13 Italian institutions. Briefly, treatment schedule was the following: oral fludarabine 40 mg/m2 on days 1–3, intravenous mitoxantrone 10 mg/m2 on day 1 every 28 days for six cycles, followed by one course of yttrium-90 (90Y)-labelled ibritumumab tiuxetan (Zevalin), which consisted in two weekly infusions of Rituximab 250 mg/m2 followed by a weight based dose of 90Y-ibritumumab tiuxetan. Primary endpoints at the time of the first analysis were complete response and hematological toxic effects, secondary endpoints were overall survival (OS) and progression free survival (PFS). Fifty-seven patients were treated with RIT after the completion of six courses of fludarabine and mitoxantrone (FN) regimen. Four patients were excluded because of disease progression (n=1) and bone marrow infiltration > 25% (n=3) at the end of the FN regimen. Median follow up at the time of the last analysis was 52 months (range 24–75). Five-year PFS was estimated to be 68%, 5-year OS was estimated to be 93.0%. Noteworthy, late hematological side effects such as myelodisplastic syndromes or acute myeloid leukemias have not been observed so far. All patients had a complete hematological recovery after the completion of the sequential treatment. 16 patients relapsed during the follow-up period and 4 patients died due to disease progression. 22 patients (38%) are in first complete remission after more than 4 years of follow-up. All relapsed patients underwent second line chemotherapy and high dose chemotherapy with stem cell rescue was performed in 4 patients. These results confirm the long term efficacy and safety of 6 cycles of fludarabine and mitoxantrone followed by consolidation with 90Y-ibritumumab tiuxetan: the 5-year PFS and OS compare favourably with the results of chemoimmunotherapy alone in untreated follicular lymphoma, with no increased incidence of secondary hematologic malignancie Disclosures: No relevant conflicts of interest to declare.

The Combination of Weekly Infusion of Rituximab and Bortezomib Is Effective in Relapsed or Refractory Indolent and Mantle Cell Lymphoma: Long-Term Results of Phase II BRIL06 Study of the Fondazione Italiana Linfomi (FIL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2735-2735 ◽  
Author(s):  
Annalisa Chiappella ◽  
Patrizia Pregno ◽  
Pier Luigi Zinzani ◽  
Amalia De Renzo ◽  
Andrea Evangelista ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
Long Term Results ◽  
High Dose ◽  
Treatment Schedule ◽  
Weekly Infusion ◽  
Mantle Cell

Abstract Background. Bortezomib, an inhibitor of the proteasome, is effective in relapsed mantle cell lymphoma (MCL) and indolent lymphomas and it is synergistic with Rituximab to enhance apoptosis and NFkB depletion. On these basis, the FIL conducted a phase II multicenter study aimed to evaluate safety and efficacy of Bortezomib in association with Rituximab in relapsed/refractory non-follicular Lymphoma (Linfocytic, LL and Marginal Zone Lymphoma, MZL) and MCL, not eligible to high dose chemotherapy with stem cell transplantation. Patients and methods. The study was a prospective single arm phase II trial, designed on Simon two-stage Optimal Design. Primary end-point was to obtain an Overall Response Rate (ORR) > 40%. The aim of this analysis is to evaluate long term follow-up of Bortezomib and Rituximab combination. A central histological revision was planned in all the patients at the enrollment. Inclusion criteria were: 18-75 years, relapsed/refractory LL, MZL, MCL after 1-4 lines. Treatment schedule was: one course of 1.6 mg/sqm Bortezomib weekly in combination with standard 375 mg/sqm Rituximab on days 1, 8, 15, 22 followed by two courses of four weekly intravenous bolus of Bortezomib alone; patients with complete (CR), partial remission and stable disease at the intermediate evaluation were planned to be given three further courses with the same schedule. Results. From September 2006 to March 2008, 55 patients were enrolled and six were excluded at central histological revision. Clinical characteristics were: median age 68 (50-74); 16 (33%) LL, 8 (16%) MZL, 25 (51%) MCL; 42 (86%) stage III/IV; 33 (67%) bone marrow involvement. Median number of previous treatments was 2 (range 1-7); 34 (69%) were Rituximab pretreated; 21 (43%) had refractory disease. Thirty (61%) patients completed the treatment and 233 courses were delivered (median: 4.7 courses/patient); 19 (39%) patients did not because of no response in 13, adverse events in five, with only one toxic death due to interstitial pneumonia. ORR was 53% (CR 26.5%); no response was seen in 43% and 4% were not evaluable for response. ORRs by clinical subgroup were: LL 37%, MZL 50%, MCL 64%; Rituximab pretreated 62%, Rituximab naïve 33%; relapsed 64% and refractory 38%. With a median follow-up of 85 months, median Overall Survival (OS) was 61.5 months (95%CI: 35.0-81.5), with 5-years OS 51% (95% CI: 36-65) and median Progression Free Survival (PFS) was 8.9 months (95%CI: 5.3-18.3), with 5-years PFS 16% (95% CI: 7-28%). Five-years PFS by histology was: 12% (95% CI: 2-31) for LL, 17% (95% CI: 5-34) for MCL and 19% (95% CI: 11-53) for MZL. PFS rates were not different between Rituximab pretreated versus naïve nor international prognostic index 1-2 versus 3-4-5 nor refractory versus relapsed. By number of previous therapies, 5-years PFS for 1 previous therapy versus 2 versus 3 or more was: 24%, 14% and 13%, respectively, p=0.36. Conclusions. Weekly infusion of Bortezomib in combination with Rituximab is effective in relapsed/refractory indolent and MCL and represents a treatment option in this setting of patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals AB0601 RAPID AND SUSTAINED EFFICACY OF AN INDUCTION TREATMENT WITH A TRIPLE THERAPY INCLUDING HIGH-DOSE INTRAVENOUS IMMUNOGLOBULINS, METHOTREXATE AND GLUCOCORTICOIDS IN ANTI-3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE MYOPATHY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1597.1-1597
Author(s):  
E. Treppo ◽  
M. Infantino ◽  
M. Benucci ◽  
V. Ravagnani ◽  
B. Palterer ◽  
...  
Keyword(s):  
Triple Therapy ◽  
Antibody Titer ◽  
Intravenous Immunoglobulins ◽  
High Dose ◽  
Sustained Remission ◽  
Red Rice ◽  
Gradual Improvement ◽  
High Doses ◽  
High Dose Ivig

Background:Anti-3-hydroxy-3-methylglutaryl-coenzime A reductase (HMGCR) myopathy is a new entity, which has been clearly associated to statin use, even if it can be diagnosed in patients without a history of exposure to statin or even in the childhood (1).Objectives:The aim of the study is to describe the efficacy of a triple therapy regimen consisting in high-doses of intravenous immunoglobulins (IVIG), methotrexate (MTX), and glucocorticoids (GC) in 16 patients with Anti-HMGCR myopathy enrolled in 6 specialized centres.Methods:A total of 16 patients with anti-HMGCR myopathy (7 females; 9 males) were collected. Mean (±standard deviation) age at the onset of disease was 72.4±10.3 years old. All patients were diagnosed having anti-HMGCR myopathy [anti-HMGCR antibodies were measured by chemiluminescence assay (BioFlash, Inova, CA)] (2). Median follow-up was 29.5 months (interquartile range: 15.75-60 months). Anti-HMGCR antibodies were available in the follow-up in 8/16 patients.Results:Thirteen out of 16 patients (81.3%) had been exposed to statin (1/13 to red rice), 3/16 (18.7%) were not exposed. As induction therapy, 11/16 patients have been treated with triple therapy (high-dose IVIG, MTX and GC), 2/16 with double therapy (high-dose IVIG and GC), 2/16 have been treated with GC alone, the patient exposed to red rice resolved only with red rice suspension. Clinical remission and normalization of CPK values within month +24 were obtained in all the patients. All the patients were in remission at the last follow-up. Gradual improvement started soon from the first month, and among the 13 patients treated with an aggressive immunosuppresssive therapy including IVIG (13/13), GC (13/13) and methotrexate (11/13), 9/13 normalized the CPK value within 6 months. Clinical and laboratory response was accompanied by significant decrease or normalization of the anti-HMGCR antibody titer. All the patients were either not taking GC (56.3%), or were taking low doses of GC (43.7%) at the last follow-up. Four patients had stopped GC within 6 months. No serious side effects were recorded. After persistent remission, a maintenance immunosuppressive therapy was then administered. Only 3 relapses in 3 different cases were recorded, all of them during drug-free remission in long-term follow-up. Reinduction was again effective in all.Conclusion:Anti-HMGCR myopathy is a rare and serious myopathy which usually affects older people during statin treatment. After statin suspension, a rapid and sustained remission can be achieved by induction with a triple aggressive therapy consisting in medium-to high doses of GC, high-dose IVIG, and MTX (3). GC should be tapered as soon as possible. Relapse appears infrequent during maintenance treatment. Monitoring anti-HMGCR antibody titer may be clinically relevant.References:[1]AL Mammen et al. N Engl J Med. 2016;374:664-9[2]Musset L et al. Autoimmun Rev. 2016;15:983-93.[3]Aggarwal A et al. Scand J Rheumatol. 2019; 1-7.Acknowledgments:We thank MD Francesca Grosso and MD Valentina Mecheri from the University of Florence, MD Angela Zuppa and MD Chiara De Michelis, from San Martino Hospital, Genova, for their valued collaboration in data collectionDisclosure of Interests:Elena Treppo: None declared, Maria Infantino: None declared, Maurizio Benucci: None declared, Viviana Ravagnani: None declared, Boaz Palterer: None declared, Marina Grandis: None declared, Martina Fabris: None declared, Paola Tomietto: None declared, Mariangela Manfredi: None declared, Arianna Sonaglia: None declared, Maria Grazia Giudizi: None declared, Francesca Ligobbi: None declared, Daniele Cammelli: None declared, Paola Parronchi: None declared, Salvatore De Vita Consultant of: Roche, GSK, Speakers bureau: Roche, GSK, Novartis, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer

Post-Operative Dysphagia in Anterior Cervical Discectomy and Fusion

2021 ◽  
pp. 000348942110155
Author(s):  
Leonard Haller ◽  
Khush Mehul Kharidia ◽  
Caitlin Bertelsen ◽  
Jeffrey Wang ◽  
Karla O’Dell
Keyword(s):  
Risk Factors ◽  
Medical Records ◽  
Assessment Tool ◽  
Demographic Data ◽  
Anterior Cervical Discectomy ◽  
Cervical Discectomy ◽  
Long Term Follow Up

Objective: We sought to identify risk factors associated with long-term dysphagia, characterize changes in dysphagia over time, and evaluate the incidence of otolaryngology referrals for patients with long-term dysphagia following anterior cervical discectomy with fusion (ACDF). Methods: About 56 patients who underwent ACDF between May 2017 to February 2019 were included in the study. All patients were assessed for dysphagia using the Eating Assessment Tool (EAT-10) survey preoperatively and late postoperatively (≥1 year). Additionally, 28 patients were assessed for dysphagia early postoperatively (2 weeks—3 months). Demographic data, medical comorbidities, intraoperative details, and post-operative otolaryngology referral rates were collected from electronic medical records. Results: Of the 56 patients enrolled, 21 patients (38%) had EAT-10 scores of 3 or more at long-term follow-up. None of the demographics, comorbidities, or surgical factors assessed were associated with long-term dysphagia. Patients who reported no long-term dysphagia had a mean EAT-10 score of 6.9 early postoperatively, while patients with long-term symptoms had a mean score of 18.1 ( P = .006). Of the 21 patients who reported persistent dysphagia symptoms, 3 (14%) received dysphagia testing or otolaryngology referrals post-operatively. Conclusion: Dysphagia is a notable side effect of ACDF surgery, but there are no significant demographics, comorbidities, or surgical risk factors that predict long-term dysphagia. Early postoperative characterization of dysphagia using the EAT-10 questionnaire can help predict long-term symptoms. There is inadequate screening and otolaryngology follow-up for patients with post-ACDF dysphagia.

scholarly journals POS0338 STEROID-SPARING EFFECT OF ANAKINRA IN GIANT-CELL ARTERITIS: A CASE SERIES WITH CLINICAL, BIOLOGICAL AND ICONOGRAPHIC LONG-TERM ASSESSMENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 397.1-397
Author(s):  
S. Deshayes ◽  
K. Ly ◽  
V. Rieu ◽  
G. Maigné ◽  
N. M. Silva ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Interleukin 1 ◽  
Oral Prednisone ◽  
Large Vessel ◽  
Daily Dose ◽  
Sparing Effect ◽  
Steroid Sparing

Background:The treatment of giant cell arteritis (GCA) relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-interleukin-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to interleukin-6, interleukin-1 also appears to play a significant role in GCA pathophysiology.Objectives:We report herein the efficacy of anakinra, an interleukin-1 receptor antagonist, in 6 GCA patients exhibiting corticosteroid dependence or resistance, specifically analyzing the outcome of aortitis in 4 of them, and including the long-term follow-up of 2 previously described patients (1).Methods:This retrospective study analyzed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis.Patients had to satisfy the following two criteria to be enrolled in this retrospective study. First, their diagnosis of GCA should be based on the fulfillment of at least 3 criteria of the American College of Rheumatology (ACR) for GCA or on the satisfaction of 2 of these criteria along with the demonstration of LVI on imaging. Second, patients should have received anakinra because of corticosteroid dependence or resistance.Corticosteroid dependence was defined as ≥2 relapses or the combination of 2 of the following criteria: a daily dose of oral prednisone >20 mg/day (or 0.3 mg/kg) at 6 months; a daily dose of oral prednisone >10 mg/day (or 0.2 mg/kg) at 12 months; and/or a treatment maintained >24 months because of a relapsing disease course. Corticosteroid resistance was defined as persistent increased inflammatory parameters at month 3 despite a steroid dosage over 0.5 mg/kg.Results:After a median duration of anakinra therapy of 19 [18–32] months, all 6 patients exhibited complete clinical and biological remission. Among the 4 patients with large-vessel involvement, 2 had a disappearance of aortitis under anakinra, and 2 showed a decrease in vascular uptake. After a median follow-up of 56 [48–63] months, corticosteroids were discontinued in 4 patients, and corticosteroid dosage could be decreased to 5 mg/day in 2 patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 hours. Three patients experienced transient injection-site reactions, and 1 patient had pneumonia.Figure 1.Steroid dosages before and after the introduction of anakinra in 6 patients with giant-cell arteritis and corticosteroid dependence or resistance. The black arrow indicates the time of anakinra introduction.Conclusion:In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.References:[1]Ly K-H, Stirnemann J, Liozon E, Michel M, Fain O, Fauchais A-L. Interleukin-1 blockade in refractory giant cell arteritis. Joint Bone Spine 2014;81:76–8.Disclosure of Interests:Samuel Deshayes: None declared, Kim LY: None declared, Virginie Rieu: None declared, Gwénola Maigné: None declared, Nicolas Martin Silva: None declared, Alain Manrique: None declared, Jacques Monteil: None declared, Hubert de Boysson Speakers bureau: Roche-Chugai, Grant/research support from: Roche-Chugai, Achille Aouba Grant/research support from: SOBI

scholarly journals Urethroplasty for failed hypospadias repair related strictures in adults: A retrospective analysis with long-term follow-up

2020 ◽  
Vol 19 ◽  
pp. e371
Author(s):  
W. Verla ◽  
F. Van Nieuwenhuyse ◽  
A. Spinoit ◽  
M. Waterloos ◽  
M. Waterschoot ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Hypospadias Repair ◽  
Long Term Follow Up
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