Proposal to establish a register for the long term surveillance of adverse events in patients with rheumatic diseases exposed to biological agents: the EULAR Surveillance Register for Biological Compounds

Ipilimumab (IPI) provides a ten-year overall survival in almost 20 % of selected patients participated in several phase II-III trials. However, the expanded access program (EAP) looks more like routine practice than like clinical trials& This is why the results of such application could be different. Here we present the long-term follow-up data of single center EAP. Ninety-six patients with disseminated melanoma progressing after at least one lines of drug therapy were included at the N.N. Petrov National Medical Research Center of Oncology. Sixty-seven (70 %) patients had stage IV M1c, 35 patients (36 %) had elevated LDH before initiating IPI therapy. All patients received IPI 3 mg / kg IV every 3 weeks for a maximum of 4 cycles. Totally, 320 cycles (mean - 3.3 per patient) were conducted. Grade 3-4 immuno-mediated adverse events (imAE) observed in 18 (19 %) patients. Three patients died of adverse events, possibly associated with ongoing therapy. The median time to progression was 3 (95 % CI, 2.4 to 3.5) mo., the median overall survival was 13 (95 % CI, 8.3 to17.6) mo. Previous immunotherapy with dendritic cell vaccines decreased the risk of death by 48 % (Log-rank p = 0.049). The wild type BRAF status increased three-year overall survival from 29 to 68 % (p = 0.042). Our data confirms long-term safety and efficacy of IPI in patients with pretreated disseminated melanoma in the close to real practice setting.

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The Safety and Effect of Local Botulinumtoxin A Injections for Long-Term Management of Chronic Pain in Post-Herpetic Neuralgia: Literature Review and Cases Report Treated with Incobotulinumtoxin A

Journal of Personalized Medicine ◽

10.3390/jpm11080758 ◽

2021 ◽

Vol 11 (8) ◽

pp. 758

Author(s):

Songjin Ri ◽

Anatol Kivi ◽

Jörg Wissel

Keyword(s):

Chronic Pain ◽

Neuropathic Pain ◽

Adverse Events ◽

Case Reports ◽

Pain Reduction ◽

Post Herpetic Neuralgia ◽

Botulinumtoxin A ◽

Incobotulinumtoxin A ◽

Term Management

There are few reports on the safety and effectiveness of long-term botulinumtoxin A (BoNT A) therapy in severe chronic pain of post-herpetic neuralgia (PHN). The literature was searched with the term “neuropathic pain” and “botulinum” on PubMed (up to 29 February 2020). Pain was assessed with the Visual Analogue Scale (VAS) before and after BoNT A therapy. A total of 10 clinical trials and six case reports including 251 patients with PHN were presented. They showed that BoNT A therapy had significant pain reduction (up to 30–50%) and improvement in quality of life. The effect duration seems to be correlated with BoNT A doses injected per injection site. Intervals between BoNT A injections were 10–14 weeks. No adverse events were reported in cases and clinical studies, even in the two pregnant women, whose babies were healthy. The repeated (≥6 times) intra/subcutaneous injections of incobotulinumtoxin A (Xeomin®, Merz Pharmaceuticals, Germany) over the two years of our three cases showed marked pain reduction and no adverse events. Adjunctive local BoNT A injection is a promising option for severe PHN, as a safe and effective therapy in long-term management for chronic neuropathic pain. Its effect size and -duration seem to be depended on the dose of BoNT A injected per each point.

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THE ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH LONG-TERM ADVERSE EVENTS AMONG PATIENTS WITH ESTABLISHED CORONARY ARTERY DISEASE: INSIGHTS FROM THE IMPROVE-IT TRIAL

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(16)30448-x ◽

2016 ◽

Vol 67 (13) ◽

pp. 447

Author(s):

Rajendra H. Mehta ◽

Jie-Lena Sun ◽

Yuliya Lokhnygina ◽

Kristy Watkins ◽

Matthew Roe ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Adverse Events ◽

High Density Lipoprotein ◽

High Density Lipoprotein Cholesterol ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Established Coronary Artery Disease ◽

Artery Disease

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Gene Therapy in Hemophilia: Recent Advances

International Journal of Molecular Sciences ◽

10.3390/ijms22147647 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7647

Author(s):

E. Carlos Rodríguez-Merchán ◽

Juan Andres De Pablo-Moreno ◽

Antonio Liras

Keyword(s):

Gene Therapy ◽

Adverse Events ◽

Factor Viii ◽

Coagulation Factor ◽

Cost Savings ◽

Factor Ix ◽

Clotting Factors ◽

Advanced Therapies ◽

Potential Benefits

Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defective circulating factor. Results have so far been encouraging in terms of levels and times of expression using mainly adeno-associated vectors. However, these therapies are associated with immunogenicity and hepatotoxicity. Optimizing the vector serotypes and the transgene (variants) will boost clotting efficacy, thus increasing the viability of these protocols. It is essential that both physicians and patients be informed about the potential benefits and risks of the new therapies, and a register of gene therapy patients be kept with information of the efficacy and long-term adverse events associated with the treatments administered. In the context of hemophilia, gene therapy may result in (particularly indirect) cost savings and in a more equitable allocation of treatments. In the case of hemophilia A, further research is needed into how to effectively package the large factor VIII gene into the vector; and in the case of hemophilia B, the priority should be to optimize both the vector serotype, reducing its immunogenicity and hepatotoxicity, and the transgene, boosting its clotting efficacy so as to minimize the amount of vector administered and decrease the incidence of adverse events without compromising the efficacy of the protein expressed.

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AB1158 VACCINATION BARRIERS IN PATIENTS WITH RHEUMATIC DISEASES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5521 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1869.2-1870

Author(s):

G. Figueroa-Parra ◽

A. Moreno-Salinas ◽

L. Santoyo-Fexas ◽

C. M. Gamboa-Alonso ◽

A. L. De-Leon-Ibarra ◽

...

Keyword(s):

Human Papillomavirus ◽

Herpes Zoster ◽

Hepatitis B ◽

Adverse Events ◽

Rheumatic Diseases ◽

Demographic Characteristics ◽

Specific Patient ◽

Increased Risk ◽

Rheumatic Patients ◽

Vaccination Barriers

Background:Patients with rheumatic diseases (RD) are at increased risk of infections, attributed to the underlying RD, comorbidities and immunosuppressive therapy, including glucocorticoids, disease-modifying antirheumatic drugs, etc. (1). While many infectious diseases can generally be prevented by vaccines, immunization rates in this specific patient population remain suboptimal (2). Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs (3).Objectives:To describe the main causes of non-vaccination in patients with RD.Methods:A self-questionnaire was applied to a sample of patients with RD in the rheumatology clinic of the university hospital “Dr. Jose Eleuterio Gonzalez” in Monterrey, Mexico between September and December 2019. The questionnaire evaluated demographic characteristics (age, gender, diagnosis) and the vaccination status for Influenza (last year), pneumococcal (last 5 years), Herpes zoster (ever), Human papillomavirus (any dose) and Hepatitis B (any dose). It also includes a question asking: If you didn’t receive any of the previous vaccines, what was the reason? (multiple-choice are shown in Table 2). Results are shown in frequencies and percentages.Table 2.Vaccination barriersN=82If you didn’t receive any of the previous vaccines,what was the reason? n (%)1)Did not was recommended22 (26.8)2) Lack of availability21 (25.6)3) Vaccines don’t work13 (15.8)4) Fear of adverse events8 (9.7)5) Previous adverse event3 (3.6)6) Other reason- Own decision8 (9.7)- Disinformation7 (8.5)Results:102 patients were evaluated: Mean age was 51.27 (SD 14.68) years; 84 (82.4%) were females; 71 (69.6%) had rheumatoid arthritis, 13 (12.7%) had systemic lupus erythematosus, 6 (5.8%) had other autoimmune diseases and 12 (11.8%) had osteoarthritis. The rate of vaccination for Influenza was 49 (48%), for pneumococcal 25 (24.5%), for Herpes zoster 5 (4.9%), for Human papillomavirus 9 (8.8%), for Hepatitis B 14 (13.7%) (Table 1). 82 (80.3%) patients reported some barriers in vaccination, from these: 22 (26.8%) did not get the recommendation from the rheumatologist, 21 (25.6%) did not found available the vaccine, 13 (15.8%) believes that vaccines don’t work, 8 (9.7%) had fear of adverse events, 3 (3.6%) reported previous adverse events, and 15 (18.2%) reported other reasons, that we classified as own decision 8 (9.7%) and disinformation 7 (8.5%) (Table 2).Table 1.Demographic characteristicsN= 102Age, years, mean (SD)51.27 (14.68)Female, n (%)84 (82.4)Diagnosis, n (%)-RA71 (69.6)-SLE13 (12.7)-OA12 (11.8)-Other AID6 (5.8)Conclusion:The main barriers in vaccination of rheumatic patients reported were the lack of availability of the indicated vaccines and the medical and patient disinformation. This problem must be combated to ensure the complete vaccination of rheumatic patients.References:[1]Ann Rheum Dis. 2020;79:39-52.[2]J Rheumatol. 2019;46(7):751-754[3]Hum Vaccin Immunother. 2013;9(8):1763-73.Disclosure of Interests:None declared

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POS0815 CLINICAL CHARACTERISTICS, IMAGING PHENOTYPE, AND LONG-TERM OUTCOMES OF TAKAYASU ARTERITIS PATIENTS WITH HYPERTENSION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3494 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 661.1-661

Author(s):

Y. Sun ◽

L. Ma ◽

H. Chen ◽

C. Rongyi ◽

L. Jiang

Keyword(s):

Blood Pressure ◽

Adverse Events ◽

Clinical Features ◽

Takayasu Arteritis ◽

Pressure Control ◽

Free Survival ◽

The World ◽

Cluster 2

Background:Hypertension occurred in 30-80% of TAK patients around the world. The occurrence of hypertension might severely worsen TAK prognosis. Nevertheless, data describing the specific imaging features in hypertensive TAK patients and the associations between hypertensive severity, blood pressure control status and long-term outcome were still lacking.Objectives:To investigate the characteristics and associations of hypertensive characteristics with adverse events-free survival in Takayasu arteritis (TAK) patients with hypertension.Methods:This research was based on a prospectively on-going observational cohort-East China Takayasu Arteritis (ECTA) cohort. In all, 618 TAK patients, who registered in the ECTA cohort up to December 2019, were enrolled. The main outcome was the adverse-events-free survival among hypertensive TAK patients during the follow-up ended on August 2020.Results:Totally, 204 (33.0%) patients suffered from hypertension, with 48 (23.5%), 62 (30.4%), and 94 (46.1%) mild, moderate, and severe hypertension, respectively. Cluster analysis indicated three imaging phenotypes for hypertensive TAK patients: Cluster 1: involvement of the abdominal aorta and/or renal artery (n=56, 27.5%); Cluster 2: involvement of the ascending aorta, thoracic aorta, and the aortic arch and its branches (n=38, 18.6%); Cluster 3: combined involvement of Cluster 1 and Cluster 2 (n=111, 54.4%). By the end of the follow-up, the blood pressure control rate was 50.8%, while the adverse-events-free survival was 67.9% in the entire hypertensive population. Multivariate Cox regression analysis indicated that well-controlled blood pressure (HR=2.13, 95%CI 1.32–3.78, p=0.047), co-existence of severe aortic valve regurgitation (HR=0.87, 95%CI 0.64–0.95, p=0.043), Cluster 1 (HR=0.69, 95%CI 0.48–0.92, p=0.017) and Cluster 3 (HR=0.72, 95%CI 0.43–0.94, p=0.048) imaging phenotype was associated with the adverse-events-free survival.Conclusion:Patients with controlled hypertension showed better adverse-events-free survival, while those with the Cluster 1 imaging phenotype were more likely to suffer from worse adverse-events-free survival. Hypertension occurred in 30-80% of TAK patients around the world. The occurrence of hypertension might severely worsen TAK prognosis.References:[1]Johnston SL, Lock RJ, Gompels MM. Takayasu arteritis: a review. J Clin Pathol 2002; 55:481–6.[2]Watanabe Y, Miyata T, Tanemoto K. Current clinical features of new patients with Takayasu arteritis observed from a cross-country research in Japan: age and sex specificity. Circulation 2015; 132:1701–9.[3]Yilmaz N, Can M, Oner FA, et al. Impaired quality of life, disability and mental health in Takayasu’s arteritis. Rheumatol. (Oxford) 2013; 52:1898–904.[4]Laurent A, Julien H, Nicolas L, et al. Takayasu arteritis in France: a single-center retrospective study of 82 cases comparing white, North African, and black patients. Medicine 2010; 89:1–17.[5]Mwipatayi BP, Jeffery PC, Beningfield SJ, et al. Takayasu arteritis: clinical features and management: report of 272 cases. ANZ J Surg 2005; 75:110–7.Disclosure of Interests:None declared

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SAT0176 THERAPEUTIC APHERESIS DURING PREGNANCY IN RHEUMATIC DISEASES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3939 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1029.2-1030

Author(s):

A. Colpo ◽

P. Marson ◽

T. Tison ◽

A. Zambon ◽

A. La Rosa ◽

...

Keyword(s):

High Risk ◽

Adverse Events ◽

Rheumatic Diseases ◽

Therapeutic Option ◽

Cardiac Activity ◽

Successful Outcome ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Total N ◽

Tertiary Center

Background:Therapeutic apheresis (TA) represents a therapeutic option in pre-existing conditions or rheumatic diseases that occur during gestation. Although pregnancy is not a contraindication itself, due to the lack of evidence-based guidelines and the alleged risk of maternal and/or fetal adverse events, there is general resistance to its application during pregnancy.Objectives:In this observational study we aimed to evaluate the efficacy and safety of TA in high-risk pregnancies in patients with rheumatic diseases, followed over a decade in a tertiary Center.Methods:Between January 2005 and April 2019, 843 TA procedures were performed during 51 pregnancies in 43 patients: 745 plasma exchange sessions and 98 immunoabsorption sessions. TA was performed in 29 (57%) pregnancies of 21 (48.8%) patients with antiphospholipid antibody syndrome (APS), in 20 (39.2%) pregnancies of 20 (46.5%) patients with congenital heart block (CHB), in 1 (1.9%) pregnancy of 1 (2.3%) patient with systemic sclerosis (SSc) and 1 (1.9%) pregnancy of 1 (2.3%) patient affected by lupic nephritis (SLE).Results:During the period considered, apheresis sessions applied to pregnant women were 7.1% of the total (n = 13.251). The average age at the first treatment was 33 years (range 24-43). The mean management age at the first apheretic treatment was 21 weeks (range 4-32). Twelve (1.4%) apheresis sessions were complicated by adverse events, none required or prolonged hospitalization. There were 44 (86.3%) live births, 3 (5.9%) spontaneous abortions and 2 (3.9%) voluntary terminations of pregnancy, 2 (3.9%) lost to follow-up. The average gestational age at birth was 35 weeks (range 24-37) and cesarean section was performed in 41 (80.4%) cases. TA was added to conventional therapy in 24/29 (82.7%) patients with APS, to the detection of fetal cardiac activity, while in 5/26 (17.3%) it was introduced when the first signs of pregnancy complications such as mild preclampsia, HELLP and IUGR were detected. TA was started within 24 hours of atrioventricular block (AVB) detection; 10/20 (50%) mothers with CHB were diagnosed with 2nd degree AVB, 9/20 (45%) with 3rd degree AVB and one (5%) with sinus bradycardia and endocardial fibroelastosis. The patient with SSc was treated with TA twice a week from the 32nd SG until delivery, which occurred at the 36th SG, due to severe IUGR and oligohydramnios. The patient with SLE complicated by lupic nephritis was treated with TA twice a week, from the 26th SG until the birth, which took place at the 31st SG.Conclusion:Our data have shown that TA in pregnancy is well tolerated. Close collaboration between rheumatologist, obstetrician and specialist in TA is essential to ensure a successful outcome of high-risk pregnancies.Disclosure of Interests: :Anna Colpo: None declared, Piero Marson: None declared, Tiziana Tison: None declared, Alessandra Zambon: None declared, Annalisa La Rosa: None declared, Ermella Zanetti: None declared, Amelia Ruffatti: None declared, Giustina De Silvestro: None declared, Ariela Hoxha Speakers bureau: Celgene, UCB, Novartis, Sanofi, Werfen

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