scholarly journals POS0600 IMMUNOGENICITY OF RITUXIMAB BIOSIMILAR GP2013: A RARE EVENT, BUT NOT WITHOUT CONSEQUENCES ...

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 534-535
Author(s):  
J. Avouac ◽  
R. Cougnaud Murail ◽  
C. Goulvestre ◽  
S. Dumas ◽  
A. Moltó ◽  
...  
Keyword(s):  
Allergic Reaction ◽  
Disease Duration ◽  
Controlled Trial ◽  
Rare Event ◽  
Treatment Discontinuation ◽  
Severe Allergic Reaction ◽  
High Antibody ◽  
Entire Treatment Period ◽  
Clinical Consequences ◽  
Antibody Levels

Background:The bioequivalence between rituximab (RTX) originator and its biosimilar GP2013 has been demonstrated in rheumatoid arthritis (RA) (1). A recent randomized controlled trial suggested in a selected population a very low immunogenicity of GP2013 in RA (<1%) (2).Objectives:To study in daily practice the risk of immunogenicity of patients treated with GP2013 for their chronic inflammatory rheumatic disorder.Methods:Prospective routine care study carried out between September 2018 and August 2020 in the Rheumatology department of Cochin Hospital. We consecutively included patients treated with the biosimilar RTX GP2013, systematically used in the department since March 2018. Samples were taken before each infusion in order to detect anti-RTX antibodies (Ab) and RTX residual concentrations by ELISA (Lisa Tracker Duo Rituximab, LTR005, Theradiag).Results:We included 159 consecutive patients treated with GP2013 (124 women, 78%) with a mean age of 59±13 years and a mean disease duration of 18±11 years. Among these 159 patients, 108 (68%) had RA and 51 had another disease (16 systemic sclerosis (SSc), 15 mixed connective tissue disease (MCTD), 5 systemic lupus (SLE), 5 inflammatory myopathies (MI), 5 undifferentiated polyarthritis, 2 juvenile idiopathic arthritis (JIA) and 3 primary Sjögren’s syndromes). 137 patients (86%) were receiving associated disease-modifying therapy (DMARD), mainly methotrexate (111/137 patients, 81%). 120 patients (75%) were in maintenance therapy with originator RTX (cumulative dose of RTX: 3.5±6g) before the switch to GP2013 in March 2018. Originator RTX was not re-established during the entire treatment period. The other 39 patients (25%) treated with GP2013 were naïve of originator RTX.The analysis of the first sample, performed before the second GP2013 infusion, identified 8 patients (5 RA, 1 SLE, 1 MCTD and 1 SSc) with positive anti-RTX antibodies (prevalence 5%), with rates varying between 6 and >100ng/mL and undetectable residual RTX concentrations. Among these 8 patients, 6 had previously received originator RTX and 2 were RTX-naïve patients. There was a trend for higher body mass index in patients with positive anti-RTX antibodies (28±7 vs. 25±6 kg/m2, p=0.12), and no association was observed between anti-RTX immunization and age, disease duration, combination with conventional DMARD, mean interval between infusions or cumulative RTX dose.Among the 8 immunized patients, two groups could be isolated: i) a group of 5 patients (3 RA, 1 SLE, 1 SSc) with low antibody levels (6-22 ng/mL) and no significant clinical consequences (absence of treatment discontinuation and loss of efficacy after 13±4 months of follow-up, only one minor allergic reaction) and ii) a group of 3 patients (2 RA, 1 MCTD) with a high antibody levels (≥100ng/mL) and meaningful clinical consequences: one severe allergic reaction during the second GP2013 infusion leading to treatment discontinuation, and a loss of efficacy with incomplete B depletion in 2 patients leading to RTX dose escalation from 500 mg to 1 g. Among the 151 patients not immunized at the time of the first sample, no severe allergic reaction and 6 minor allergic reactions were noted under GP2013.Conclusion:The immunogenicity of patients treated with RTX is a rare event with possible clinical and biological consequences, especially in patients with high antibody levels.References:[1]Smolen et al, Ann Rheum Dis 2017[2]Tony et al, Arthritis Care Res 2019Disclosure of Interests:None declared

Abstract 3712: A Randomized Placebo-Controlled Trial of a Conjugate Nicotine Vaccine (NicVAX®) in Smokers Who Want to Quit: 12 Month Results

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Stephen I Rennard ◽  
Douglas E Jorenby ◽  
David Gonzales ◽  
Nancy A Rigotti ◽  
Arjen de Vos ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Group Analysis ◽  
High Responder ◽  
High Antibody ◽  
Continuous Abstinence ◽  
Antibody Titers ◽  
Double Blinded ◽  
Antibody Levels

Background: Cigarette smoking triples the risk of dying from heart disease among middle-aged men and women. A nicotine vaccine (NicVAX®) has been developed to produce nicotine-specific antibodies as a means of reducing entry of nicotine into the brain as an aid to smoking cessation. Objective: To assess 12-month safety, efficacy and immunogenicity of NicVAX in smokers who want to quit. Method: Randomized, double-blinded, placebo-controlled multicenter clinical trial with 2 dose levels of NicVAX (200μg & 400μg) and 2 schedules. Generally healthy adults who smoked ≥ 15 cigarettes/day were recruited. Subjects were randomized 2:1, active:placebo, at 9 sites in the US. The primary endpoint was self reported continuous abstinence for weeks 19 – 26 confirmed by expired CO levels of ≤ 8 ppm. Secondary endpoints include point prevalence abstinence at 12 months. Results: 301 subjects (52% female) with a mean age of 48, smoking on average 24 cigarettes/day were enrolled. A pre-defined analysis of antibody levels for subjects receiving NicVAX were reviewed and divided into low and high responder groups, with the top 30 th percentile representing the high responder group. Analysis for the primary endpoint demonstrated that 15/61 (24.6%) of subjects having the highest antibody titers achieved an 8 week period of continuous abstinence between weeks 19 –26, compared to 13/100 (13.0%) for the subjects who received placebo (p=0.04). In contrast, the quit rate for those subjects that did not achieve a high antibody titer was not significantly different from placebo (14/140, 10%). There was a significant relationship between anti-nicotine antibody levels and continuous abstinence from smoking (p=0.0001). NicVAX was well-tolerated and showed no differences in adverse events or in local/systemic reactions between placebo and each active vaccine group. Conclusion: Proof-of-concept has been established by the strong correlation of high antibody titers with smoking abstinence. Interim data (6 months post vaccination) demonstrate that generating antibodies to nicotine may be a useful approach for aiding smoking cessation. This study will be completed in Sept 2007. Immunogenicity, sustained smoking cessation and relapse rates at 12 months after vaccination will be presented.

Management of Haemophilia A with Antibodies - The Effect of Combined Treatment with Factor VIII, Hydrocortisone and Cyclophosphamide

1985 ◽  
Vol 54 (04) ◽  
pp. 776-779 ◽  
Author(s):  
U Hedner ◽  
L Tengborn
Keyword(s):  
Factor Viii ◽  
Combined Treatment ◽  
Factor Ix ◽  
Treatment Schedule ◽  
High Antibody ◽  
Anamnestic Response ◽  
Short Intervals ◽  
Low Responders ◽  
Antibody Levels ◽  
High Responders

SummaryImmune tolerance has by several methods been induced in haemophiliacs with antibodies. A conversion of “high responders” into “low responders” was previously reported after repeated moderate factor IX doses over periods of 7-10 days in combination with cyclophosphamide and steroids in two patients with haemophilia B and inhibitors. This paper reports similar results in a heamophilia A patient by giving factor VIII, cyclophosphamide, and steroids during relatively short periods of time (7-8 days). The anamnestic response markedly decreased already following the first treatment and never exceeded a level of 1 u/ml (˜ 3 BU/ml) even when boosted with ordinary factor VIII doses for only 3 days. It is concluded that the markedly decreased secondary antibody response is most probably the result of factor VIII given at short intervals (twice a day) for periods of up to about one week when given in combination with cyclophosphamide and steroids. The same effect may be achieved by other methods. The treatment schedule suggested in the present paper is, however, simple and avoids long periods of high antibody levels. Furthermore, the total factor VIII dose used is lower than suggested in most other treatment schedules, which makes the treatment substantially less expensive.

scholarly journals POS0941 IN SPONDYLOARTHRITIS PATIENTS THE PRESENCE OF COMORBIDITIES IS AN INDEPENDENT PREDICTOR OF INSUFFICIENT RESPONSE TO THERAPY WITH BIOLOGIC AGENTS AND TREATMENT DISCONTINUATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 733.2-734
Author(s):  
I. Flouri ◽  
N. Kougkas ◽  
N. Avgustidis ◽  
A. Repa ◽  
A. Eskitzis ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Disease Duration ◽  
Cox Regression ◽  
Independent Predictor ◽  
Response To Therapy ◽  
Treatment Discontinuation ◽  
Randomized Controlled Studies ◽  
Insufficient Response ◽  
The Impact

Background:Long-term observational studies of patients under biologic disease-modifying anti-rheumatic drug (bDMARD) therapies in routine clinical practice can provide us with important data regarding patients with comorbidities, who are usually excluded from randomized controlled studies.Objectives:To study the impact of comorbidities in the outcome (response and persistence to therapy) of patients with spondyloarthritis (SpA) receiving bDMARDs in real-world clinical practice.Methods:Prospective study of all patients who start a bDMARD in a tertiary centre University Hospital after their consent. All patient comorbidities [among a list of approximately 100 pre-specified major comorbidities] are registered by treating physicians at baseline and during follow-up.Comorbidities were studied as total Comorbidities Count (CC) and rheumatic disease comorbidity index (RDCI). Statistical analyses were performed using logistic and Cox regression models, adjusting for the potential confounding of age, sex, disease duration, diagnosis (axial vs. peripheral SpA), number of previous conventional synthetic and biologic DMARDs, year of therapy start, and co-administered methotrexate and corticosteroids (yes/no). Analyses of response to therapy also included baseline BASDAI or ASDAS indices as confounding variables.Results:A total of 603 biologic treatments (1st: 298, 2nd: 157, ≥3rd: 148) were analyzed. Half (51%) of the patients were female, 413 patients had axial SpA (AxSpA) and 190 peripheral SpA (perSpA). At baseline, median (IQR) age: 48 (38-57) years, disease duration: 11 (4-19) years, CC: 2 (1-4) and RDCI: 1 (0-2). Both comorbidity indices were significantly higher in perSpA compared to AxSpA (p<0.001).At 6 months of therapy, 31% of patients with AxSpA achieved BASDAI50 and 39% had ASDAS-ESR < 2.1. Higher CC was an independent predictor of insufficient response according to BASDAI50 [OR (95%) = 0.70 (0.52-0.94), p=0.019] and higher RDCI was predicting failure to achieve ASDAS-ESR < 2.1 [OR (95%) = 0.59 (0.37-0.94), p=0.027]. Other independent predictors of non-response were age, longer disease duration and (for ASDAS-ESR<2.1) higher baseline disease activity.During 1405 patient-years of follow-up, 349 (58%) treatments were discontinued. The adjusted hazard ratio for bDMARD discontinuation within the first 2 years of treatment due to insufficient response was doubled in patients with CC ≥2 versus those with CC ≤1 [HR = 2.27 (1.14-4.53), p=0.020] or with RDCI ≥1 (vs. RDCI = 0) [HR = 2.23 (1.22-4.07), p=0.009]. Comorbidities’ indices were not significant predictors of treatment discontinuations due to adverse events.Conclusion:The presence of comorbidities in patients with SpA is an independent predictor for insufficient 6-month response to bDMARDs and resultant treatment discontinuation due to failure.Acknowledgements:This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (ΙΚΥ).Disclosure of Interests:None declared

Relapse Following Combined Treatment Discontinuation in a Placebo-Controlled Trial for Panic Disorder

2008 ◽  
Vol 196 (7) ◽  
pp. 548-555 ◽  
Author(s):  
Susan D. Raffa ◽  
Jill A. Stoddard ◽  
Kamila S. White ◽  
David H. Barlow ◽  
Jack M. Gorman ◽  
...  
Keyword(s):  
Panic Disorder ◽  
Controlled Trial ◽  
Combined Treatment ◽  
Treatment Discontinuation

scholarly journals Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial

Nutrients ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 228
Author(s):  
Anxo Fernández-Ferreiro ◽  
Francisco J. Formigo-Couceiro ◽  
Roi Veiga-Gutierrez ◽  
Jose A. Maldonado-Lobón ◽  
Ana M. Hermida-Cao ◽  
...  
Keyword(s):  
Immune Response ◽  
Controlled Trial ◽  
Severe Disease ◽  
Nursing Home Residents ◽  
Vaccination Schedule ◽  
Elderly Subjects ◽  
Double Blind ◽  
Iga Antibody ◽  
Specific Igg ◽  
Antibody Levels

Elderly people are particularly vulnerable to COVID-19, with a high risk of developing severe disease and a reduced immune response to the COVID-19 vaccine. A randomized, placebo-controlled, double-blind trial to assess the effect of the consumption of the probiotic Loigolactobacillus coryniformis K8 CECT 5711 on the immune response generated by the COVID-19 vaccine in an elderly population was performed. Two hundred nursing home residents >60 yrs that had not COVID-19 were randomized to receive L. coryniformis K8 or a placebo daily for 3 months. All volunteers received a complete vaccination schedule of a mRNA vaccine, starting the intervention ten days after the first dose. Specific IgG and IgA antibody levels were analyzed 56 days after the end of the immunization process. No differences between the groups were observed in the antibody levels. During the intervention, 19 subjects had COVID-19 (11 receiving K8 vs. 8 receiving placebo, p = 0.457). Subgroup analysis in these patients showed that levels of IgG were significantly higher in those receiving K8 compared to placebo (p = 0.038). Among subjects >85 yrs that did not get COVID-19, administration of K8 tended to increase the IgA levels (p = 0.082). The administration of K8 may enhance the specific immune response against COVID-19 and may improve the COVID-19 vaccine-specific responses in elderly populations.

Brain death in pregnancy: what will be left of the life of foetus?

2020 ◽  
Vol 69 (3) ◽  
pp. 281-291
Author(s):  
Matteo Gulino ◽  
Gianluca Montanari Vergallo ◽  
Rosagemma Ciliberti ◽  
Antonio G. Spagnolo
Keyword(s):  
Brain Death ◽  
Human Life ◽  
Rare Event ◽  
High Impact ◽  
Social Implications ◽  
Vital Functions ◽  
Clinical Consequences ◽  
Potential Impact ◽  
The Moment ◽  
In Pregnancy

Brain death in pregnancy (BDinP) has been described in literature as a “rare event” and “hopeless condition for patients”, who has a devastating potential to negatively affect the poetry of the moment of welcoming a new human life to the world. Clinical consequences of BDinP are extremely dangerous for the life of a foetus that, without prompt medical actions, is doomed to suffer the same fate as the mother. Modern medical techniques make it possible to maintain basic vital functions of the pregnant woman for months, in order to achieve a level of development of the foetus. Although maternal somatic support requires the consideration of specific medical parameters, from a bioethical standpoint, this option gives rise to multiple ethical and social implications. In this manuscript, we identify the main ethical and social implications about maternal somatic support, including the potential impact on the clinical practice of medical staff, and discuss some Italian high-impact media cases.* The authors contributed equally to the work.

scholarly journals WITHDRAWN: Severe allergic reaction following Histrelin implant (Supprelin LA)

2020 ◽  
pp. 101398
Author(s):  
Sara Donnelly ◽  
Dana Shuriff ◽  
Steven Stylianos ◽  
Jeffrey Zitsma
Keyword(s):  
Allergic Reaction ◽  
Severe Allergic Reaction
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