Impact of ICER Assessments on Payer Decision Making in the United States

Objectives: To evaluate how payers utilize Institute for Clinical and Economic Review (ICER) assessments to inform coverage or formulary decisions. Method(s): Double-blinded, web-based survey was fielded through Xcenda's research panel, the Managed Care Network, from June to July 2022. Result(s): A total of 51 payers from health plans (n=27), integrated delivery networks (n=12), and pharmacy benefit managers (n=12) participated in the survey. When assessing the usefulness of ICER's value assessment framework (VAF) to inform formulary decisions within their organizations, 57% of payers indicated it was extremely/very useful, 33% indicated somewhat useful, and 10% indicated not at all/not very useful. Most respondents (73%) agreed that ICER assessments are aligned with their organization's internal assessment. Utilization of ICER's VAF was most prevalent in high-cost drug or disease states (78%), rare/orphan disease states (71%), and oncology/hematology disease states (67%). Payers reported less use in primary care disease states (29%), COVID-19 (8%), and digital therapeutics (4%). In the last 24 months, 20% of payers reported ICER's recommendations often influenced coverage decisions, 59% indicated occasional influence, and 22% indicated no influence. In the last 24 months, payers indicated the top 5 ICER assessments that influenced their coverage decisions included high cholesterol (38%), Alzheimer's disease (36%), atopic dermatitis (33%), multiple myeloma (31%), and chemotherapy-induced neutropenia (28%). ICER assessments that were less impactful included beta thalassemia (3%), digital health technologies (3%), and supervised injection facilities (3%). Payers reported using ICER assessments to inform both expanded and restricted coverage decisions. Conclusion(s): Payers find ICER's VAF useful to inform their organization's formulary decisions. ICER's assessments often align with payers' internal assessments and are most frequently utilized for high-cost drugs or disease states. Payers indicate ICER assessments have affected both expansion and restriction in their coverage policies.Copyright © 2023

De Novo Experience of Individuals with Li-Fraumeni Syndrome: Sometimes the people in your family are never going to be the ones who understand best

Background/Objectives: Li-Fraumeni Syndrome (LFS) is a rare hereditary cancer predisposition syndrome characterized by high lifetime risks for multiple primary malignancies. Although most individuals with LFS inherit a pathogenic TP53 variant from a parent, approximately 20% have de novo variants with no suggestive family cancer history. This may result in an LFS experience distinct from individuals with affected relatives. This multi-case study report examines the unique psychosocial experiences of three young adults with de novo TP53 variants. Method(s): The National Cancer Institute's LFS study (NCT01443468) recruited adolescents and young adults (AYAs;aged 15-39 years) with LFS for qualitative interviews. Three participants had a de novo TP53 variant and a personal cancer history. An interprofessional team analyzed interview data using extended case study and narrative methods. Result(s): De novo participants lacked familiarity with LFS to situate a cancer diagnosis, interpret genetic test results, or adjust to chronic cancer risk. Communicating with and receiving support from family was challenged by their lack of common experience. De novo participants experienced socioemotional isolation, which was amplified during the COVID-19 pandemic. To cope, they sought support in online rare disease communities or through mental health providers. Conclusion(s): Individuals with de novo variants may lack familial guides and familiar providers to address disease management and uncertainty. Specialty health and mental health providers may support de novo patients across hereditary cancer syndromes by validating their uncertainties and connecting them with diseasespecific patient advocacy groups that support adjustment to chronic cancer risk.

Evaluation of the Updated French Autorisation D'Acces Precoce (AAP) Early Access Authorization Pathway

Objectives: To evaluate products reviewed by the Transparency Committee (TC) of the Haute Authorite de Sante (HAS) under the Autorisation d'Acces Precoce (AAP) Early Access Authorization (EAA) pathway and investigate any trends. Method(s): All 97 AAP submissions are publicly available from HAS and were evaluated on or before January 4th, 2023. The TC's opinion was reviewed to obtain the outcome, decision date, therapeutic area, and reasons for rejection. Results were tabulated and descriptive statistics were compiled. Result(s): In total, 79 of the 97 (81%) submissions evaluated were approved for EAA, including renewals of previously granted authorization (6 of 79);18 were rejected. Of the 97 submissions, 35% were indicated for the treatment of solid cancers, 14% for haematological cancers, 10% for ultra-rare diseases, 10% for infectious diseases, 4% for rare diseases, 4% for autoimmune diseases, 4% for skin diseases, and 2% for weight management. Notable approved submissions including those indicated for rare diseases, cancer, autoimmune diseases, and COVID-19, with 93%, 90%, 75%, and 63% of these submissions being granted EAA, respectively. Across the 18 unsuccessful submissions, the main reasons cited for rejection were insufficient efficacy and safety data (78%), lack of innovation compared to existing treatment options (61%), the availability of existing treatment options (56%), and the treatment not being rare enough to qualify for special consideration (28%). Conclusion(s): Since its inception in July 2021, the AAP has proven to be a popular program. As awareness of the program grows and more information becomes available about its benefits and eligibility criteria, it is likely that the number of submissions will continue to increase. However, given the link between submission success and the quality of available data (including a data collection plan), it is recommended manufacturers provide robust evidence to bolster their submissions.Copyright © 2023

Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases: Third of Three Sets of Expanded Proceedings from the 2020 ISCTM Autumn Conference on Pediatric Drug Development

This article expands on a session, titled "Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases," that was presented as part of a two-day meeting on Pediatric Drug Development at the International Society for Central Nervous System (CNS) Clinical Trials and Methodology (ISCTM) Autumn Conference in Boston, Massachusetts, in October 2020. Speakers from various areas of pediatric drug development addressed a variety of implications of including children in drug development programs, including implications for rare/orphan diseases. The speakers have written summaries of their talks. The session's lead Chair was Dr. Joan Busner, who wrote introductory and closing comments. Dr. Simon Day, regulatory consultant, outlined some of the past mistakes that have plagued trials that did not consult with patient groups in the early design phase. Dr. Atul Mahableshwarkar provided an industry perspective of a recent trial that benefited from the inclusion of patient input. Drs. Lucas Kempf and Maria Sheean provided regulatory input from the perspectives of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively. Dr. Judith Dunn outlined a novel approach for assessing and rank ordering patient and clinician clinical meaningfulness and the disconnect that may occur. Dr. Busner provided closing comments, tied together the presented issues, and provided a synopsis of the lively discussion that followed the session. In addition to the speakers above, the discussion included two representatives from patient advocacy groups, as well as an additional speaker who described the challenges of conducting a pediatric trial in the US and European Union (EU), given the often competing regulatory requirements. This article should serve as an expert-informed reference to those interested and involved in CNS drug development programs that are aimed at children and rare diseases and seek to ensure a patient-centric approach.Copyright © 2023, Matrix Medical Communications. All rights reserved.

Identification of Patients Diagnosed with Rare and Emerging Diseases Utilizing the Trinetx Network: A Case Study of African and American Trypanosomiasis

Objectives: Due to large sample sizes, electronic medical records (EMR) databases have the potential to provide pivotal insights into patients diagnosed with rare, orphan, or emerging diseases. This study aimed to explore the patient profile of African and American trypanosomiasis, both vector-borne parasitic diseases, pre-and post the COVID-19 pandemic using the TriNetX Network. Method(s): From Jan 1, 2018 - Nov 30, 2019 (pre-COVID) and Jan 1, 2020 - Nov 30, 2021 (post-COVID) patients were queried from the TriNetX Global health research network, inclusive of 88 million patients from the United States (US), Europe, the Middle East, Africa, Latin America, and Asia Pacific. Eligible patients with an ICD-10 diagnosis code of African trypanosomiasis or American trypanosomiasis were identified (2280 patients on 22-Dec-2022) and analyzed separately, pre- and post-COVID. Result(s): We identified 340 patients pre- and 960 patients post-COVID with African trypanosomiasis and 960 patients pre- and 190 patients post-COVID with American trypanosomiasis. Most patients resided in the US. Pre-COVID African trypanosomiasis patients had a mean age of 38 and were 59% female while post-COVID patients had a mean age of 34 and were 57% female. Pre-COVID American trypanosomiasis patients had a mean age of 49 and were 57% female while post-COVID patients had a mean age of 49 and were 53% female. Top co-diagnoses included diseases of the respiratory (85%, 84%) and nervous systems (82%, 79%) for patients with African trypanosomiasis and diseases of the digestive (69%, 54%) and circulatory systems (68%, 61%) for patients with American trypanosomiasis in both the pre- and post-COVID cohorts, respectively. Conclusion(s): Using real-world EMR data we were able to obtain patient profiles for a rare disease (African trypanosomiasis) and a common, emerging disease (American trypanosomiasis). This informationsupportsutilizing EMR data for describing patient populations in rare, orphan, or emerging diseases, which may aid drug development for these indications.Copyright © 2023

Allergic reactions of COVID-19 vaccine based on mRNA-LNP and its pharmacokinetics in vivo

Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

A Thorn in his Side

History: A 20 year old D1 men's basketball player with a history of COVID the month prior presented with worsening low back pain. He denied any injury, but reported the pain started as low back discomfort after a basketball game the week prior. He noted a progression and radiation of pain down his right lower extremity to his toes. He had tried physical therapy and dry needling, as well as cyclobenzaprine and naproxen from team physicians with mild improvement. The pain worsened and he went to the ED for evaluation. He was afebrile and had a lumbar radiograph with no acute fracture, grade 1 anterolisthesis of L5 on S1. He was discharged home with norco. Over the next 2 days, he developed chills and in the context of his worsening back pain, his team physicians ordered an MRI. Physical Exam: BMI 26.9 Temp 97.9degree Heart rate: 73 Respiratory rate 14 BP: 124/64 MSK: Spine- Intact skin with generalized pain over lumbar area, worse over the right paraspinal musculature. 5/5 strength of bilateral lower extremity flexion and extension of his hips, knees, and plantar and dorsiflexion of ankles and toes. Bilateral intact sensibility in the sciatic, femoral, superficial, and deep peroneal, sural, and saphenous nerve distributions. Slightly diminished sensibility over the right deep peroneal nerve distribution compared to left. 2/4 patellar and achilles DTRs. No clonus, downgoing Babinski sign. Positive straight leg raise at 45 degrees with the right lower extremity. Differential Diagnosis: 141. Sciatica 142. Lumbar Muscle Strain 143. Disk Herniation 144. Spondylolisthesis 145. Vertebral Osteomyelitis Test Results: CBC:WBC10, HGB13.2, neutrophils 75.7% (red 45%-74%). Unremarkable CMP. CRP =7.31, ESR 23 Blood culture negative, throat culture negative. TB test negative. COVID test negative. Flu test negative. Urine culture and UDS negative. HIV test negative. Procalcitonin of 0.07. IR guided aspiration and bacterial Culture yielded MSSA. MRI w/contrast: showing L1-L4 facet edema concerning for infectious spondylitis, intramuscular, and epidural abscess. Final Diagnosis: Acute intramuscular abscess, vertebral osteomyelitis, with epidural abscess. Discussion(s): Vertebral osteomyelitis is a serious but quite rare disease in the immunocompetent, elite athlete population. Staphylococcus Aureus is the culprit a majority of the time, with only 50% of cases showing neurologic symptoms. This case was unique given the proximity to a dry needling treatment which is the only explainable vector of infection, normal blood cultures in this disease which hematogenously spreads, negativeHIV and other infectious disease testing, and otherwise benign history. Early recognition of this disease yields better outcomes and reduces incidence of severe debility. 5% to 10%of patients experience recurrence of back pain or osteomyelitis later on in life. Outcome(s): Patient was hospitalized and started on Cefepime and Vancomycin. Had an echocardiogram revealing changes consistent with athlete's heart without signs of vegetation on his cardiac valves. Neurosurgery declined to treat surgically. He continued to improve until he was ultimately discharged on hospital day 4 with a picc line and Nafcillin and was later changed to oral augmentin per ID. Follow-Up: By his 6 week follow-up visit with infectious disease and the team physicians, his back pain had completely resolved and was cleared to start a return to play protocol. There was no progression of disease since starting antibiotics, and no recurrence of back pain since treatment.

Beyond the Exscalate4CoV Project: LIGATE and REMEDI4ALL Projects

In the last 2 years, the SARS-CoV-2 (COVID-19) pandemic demonstrated that rapid response to outbreaks with readily effective treatments represents a primary health and societal priority. At the same time, we became conscious that technological resources are often not used in the most efficient manner. The LIGATE and REpurposing MEDIcines For All (REMEDI4ALL) projects started on the large-scale mobilization efforts of the EXaSCale smArt pLatform Against paThogEns (Exscalate4Cov) project with the aim to apply cutting-edge technologies in drug discovery, sustain the fight against future pandemics, and promote the everyday fight against rare diseases. In particular, the LIGATE project, using the drug-discovery platform Exscalate, intends to boost the virtual screening of drug campaigns at an extreme scale in terms of performance and streamline the drug-development process. The aim of the REMEDI4ALL project is to collect sciQ1entific expertise and innovative technology platforms for the repurposing of medicines to treat rare diseases or other pathologic conditions with no current therapy. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Utilizing telehealth to create a clinical model of care for patients with Batten disease and other rare diseases.

The COVID-19 pandemic transformed the delivery of healthcare across the world. Telehealth has emerged as the primary method for providing healthcare early in the pandemic. Patient and healthcare provider views of the effectiveness of telehealth services are encouraging and support the long-term use of telehealth services in clinical practice. Telehealth may provide a strategy that has far-reaching benefits for diverse patient populations, such as patients with Batten disease and other rare diseases, who face additional barriers to accessing subspecialty healthcare services. The aims of this paper, through the experience of a single Batten Disease Center of Excellence, are to (1) review the benefits and barriers involved in the delivery of telehealth services to patients with rare diseases; (2) discuss components of a model for clinical care that utilizes telehealth services for patients with Batten disease; (3) discuss limitations and future directions of using telehealth in patients with rare diseases. Healthcare systems should consider building clinical models that utilize telehealth services to provide multidisciplinary services to patients with rare diseases. There are numerous benefits in using telehealth that can enhance and expand service delivery between the patient and clinician. Telehealth services can also improve provider-to-provider communication and collaboration when providing clinical care to individuals with rare diseases. Although there are many benefits to utilizing telehealth services in provision of care to patients with rare diseases, it is important to consider factors that may limit or add additional barriers prior to implementing telehealth services. There is a need for future collaborative research to examine and compare the effectiveness and outcomes of telehealth services with standard of care services that are provided in-person. Future research should also examine how to reduce the challenges and barriers associated with the implementation of telehealth services. Plain language summary: What is telehealth? Telehealth is defined by the US Department of Health Resources and Services Administrations1 as the "use of electronic information and telecommunication technologies to support long-distance clinical healthcare, patient and professional health-related education, public health, and health administration. Technologies include video conference, the internet, store-and-forward imaging, streaming media, and terrestrial and wireless communication." What was the aim of this review? This review was conducted to guide a clinical model using telehealth services for patients with Batten disease and other rare diseases based on the experiences of a single Batten Disease Center of Excellence. Why is this important? Individuals with rare diseases may face multiple barriers to accessing clinical services. Local doctors and treatment providers, such as speech therapists, occupational therapists, physical therapists, and psychologists, may not have knowledge of rare diseases or how to manage symptoms and disease progression, or how to guide treatment services. Other barriers may also include:• Lack of local resources;• Increased caregiver stress;• Difficulty obtaining a correct diagnosis.There are numerous benefits to using telehealth services for both patients with rare diseases, such as:• Convenience;• Cost savings;• Improved access to care;• Ability to see multiple providers that can help with symptom monitoring, assessment, and treatment services. Where do we go from here? It is important to consider limitations when creating a model for clinical care for patients with rare diseases. Some limitations to think about are:• Clinician and organization familiarity with telehealth;• Reimbursement and coverage from insurance companies for telehealth;• Security and privacy of patient information;• Training of telehealth providers;• Logistical factors, including use of equipment, internet/connectivity, and technical troubleshooting.Future directions should involve collaborative research that studies the effectiveness, feasibility, and perceptions of families of rare diseases and providers that use telehealth for clinical healthcare services. Research should also further study and consider ways to improve barriers and challenges associated with implementing telehealth systems into existing healthcare systems.

Improving Detection of Alpha-1 Antitrypsin Deficiency: Role of the Allergist.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that manifests as lung and/or liver disease. Because symptoms of AATD overlap with those of common pulmonary and hepatic conditions, AATD is often misdiagnosed, which has resulted in substantial underdiagnosis of AATD worldwide. Although screening patients for AATD is recommended, the lack of procedures to facilitate testing remains a barrier to accurate diagnosis of AATD. Delays in AATD diagnosis can worsen outcomes for patients by postponing appropriate disease-modifying treatments. Patients with AATD-related lung disease experience symptoms similar to other obstructive lung disorders and are often misdiagnosed for years. In addition to existing screening guidelines, we recommend that screening for AATD become a standard part of allergists' workups of patients with asthma and fixed obstructive disease, chronic obstructive pulmonary disease, bronchiectasis without known origin, and patients under consideration for treatment with biologics. This Rostrum article reviews screening and diagnostic tests available in the United States and emphasizes evidence-based strategies to increase testing frequency and improve AATD detection rates. We underscore the pivotal role of allergists in managing care for patients with AATD. Finally, we urge health care providers to be aware of potentially poor clinical outcomes among patients with AATD during the coronavirus disease 2019 pandemic.

Going Virtual During Covid with the NCI-Connect Cares (Coping, Advocacy, Resources, Education, Support) Group for Rare Brain and Spine Tumor (RBST) Patients and their Families

Background/Purpose: RBST patients have limited supportive care resources and feel secluded as few healthcare providers have expertise in these diseases. The NCI-CONNECT specialized clinic for adults with RBSTs created a multidisciplinary approach with a genetic counselor, knowledgeable healthcare team, and group sessions with a health and wellness counselor (CARES). The CARES sessions created an educational and supportive space for patients to share their unique experiences. We report the adaptation of the CARES group that evolved from in-person to virtual during COVID. Method(s): Patients with RBSTs and their families attended weekly (1 h) groups at their clinic appointments. The CARES group leaders (A.A, S.S) led wellness/coping presentations (15-20 min) and a guided discussion on the topic. In 2021, the COVID pandemic shifted the group to monthly virtual meetings, and educational content was shared via a closed-Facebook group and NCI-CONNECT website. Six groups included presenters within Neuro-Oncology, shortened prerecorded presentations (10 min) allowing for more engagement opportunities, and a coping activity concluded the meeting. Emailed survey feedback was requested (5 out of 13 completed). Result(s): On average, six patients attended each group. Topics included mindfulness, distress, relational challenges, body image, and an educational series on symptom management. All presentations can be found on the NCI-CONNECT website. Patients reported enjoyment in the ability to connect with others, with 80% preferring monthly virtual meetings. Open-ended comments noted that hearing other patients' stories created connections patients expressed they needed. Conclusions and Implications: The virtual CARES group created an accessible space for RBST patients to build relationships and gain support to manage the uncertainties of coping with a rare disease during a time of physical isolation. Patient responses capture the need to continue the group further. Future work will focus on expanding the group based on patient needs and building metrics to understand the overall group benefits in a virtual world.

Hairy Cell Leukemia in a Filipino Male during the COVID-19 Pandemic - Report of a Rare Case

Hairy cell leukemia (HCL) is a rare, chronic, mature B-cell lymphoproliferative disorder accounting for 2% of all leukemias. In this paper, we would like to present our experience in the management of HCL in a financially limited setting where other diagnostic tests and chemotherapy are unavailable. The case report aims to emphasize the recognition of the distinctive morphology of hairy cells in the peripheral blood in the consideration of the initial diagnosis. A 60-year-old Filipino male was incidentally found to have anemia, thrombocytopenia and an absolute neutrophilic count below 1,000 in a pre-operative clearance for elective herniorrhaphy. Blood smear revealed atypical lymphocytes with hair like cytoplasmic projections. CT-scan of the abdomen showed splenomegaly and prominent paraaortic nodes. Flow cytometry of the bone marrow aspirate was consistent with an involvement of a Mature B cell neoplasm markers CD19, CD20, CD22 and surface immunoglobulin lambda and hairy cell leukemia markers CD11c, CD103 and CD25. He responded to six-weekly sessions of Cladribine with remission of the bone marrow and hematologic parameters. HCL is a rare type of a mature B cell neoplasm characterized by pancytopenia, splenomegaly, bone marrow fibrosis and the presence of atypical lymphoid cells with hairy projections in blood, bone marrow and spleen. Immunophenotyping express CD11c, CD103, CD123, and CD25. BRAF V600E mutation is the disease defining genetic event. Cladribine and Pentostatin are the first line of treatment. Cases of leukemia can be easily overlooked because of the mild derangement in the complete blood count. A meticulous differential review of the atypical lymphocyte, is the first step in the diagnosis of this rare disease.Copyright © 2022, Philippine College of Physicians. All rights reserved.

Subcutaneous administration of C1 inhibitor concentrate: Case report of a pediatric patient with hereditary angioedema

Case report Background: Hereditary angioedema (HAE) is a rare disease that usually manifests during childhood and is characterized by recurrent swelling episodes in various body tissues. Effective treatment options, including replacement therapy with C1 inhibitor (C1-INH) concentrate, are available for acute attacks and, for patients with high disease burden, for prophylaxis. More convenient than intravenous (IV) injections, and better suitable for patients with difficult venous access, is subcutaneous (SC) administration. However, treatment with SC prophylactic C1-INH is not yet approved in Europe for children < 12 years of age. Case Description: The boy presented to our clinic in 2014 at the age of 3, with a diagnosis of HAE due to C1-INH deficiency. During the last 3 months, he had been given IV C1-INH concentrate on-demand for HAE attacks. During the following year, the boy experienced monthly attacks at different body sites and had to be hospitalized several times for edema of the extremities and face, and abdominal colicky pain. At 5 to 6 years of age, attack frequency increased to once weekly and a first swelling of the trachea with dyspnea occurred. Over time, this led to repeated occurrence of panic attacks and psychological problems, which were exacerbated by social distancing during the coronavirus disease-19 pandemic. To mitigate disease burden, his therapy was switched to weekly prophylaxis with IV C1-INH, and the bradykinin receptor inhibitor icatibant was kept on hand as emergency medicine. Less than half a year later, attack frequency increased again and the regimen was changed to twice weekly. This led to drastic deterioration of venous access, so that a switch to SC prophylaxis became inevitable. The patient, now 10 years old, and his mother were trained in SC injection techniques and since June 2021, they administer twice weekly SC C1-INH (2000 International Units) at home, with no breakthrough attacks and significant improvement of quality of life. Conclusion(s): Because of high disease burden and impairment of quality of life due to high edema frequency, routine prophylaxis was chosen. In patients receiving frequent IV prophylaxis, occurrence of breakthrough attacks and deterioration of venous access warrants a switch to SC treatment. In the present case, this switch was unavoidable, although this treatment option is not approved for children. It allows the boy to self-administer his C1-INH and has improved his quality of life significantly.

Glial fibrillary acidic protein astrocytopathy in a patient with recent mRNA SARS-CoV-2 vaccination: COVERSHEET

Background: Literature describing triggers of GFAP astrocytopathy (GFAP-A) is limited. We report a case of GFAP-A in a patient with recent messenger ribonucleic acid (mRNA) severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) vaccination and discuss the possible pathogenesis. Case description: A 45-year-old gentleman presented with features of meningoencephalitis 31 days after the first dose and 4 days after the second dose of mRNA SARS-CoV-2 vaccination. He sequentially developed brainstem/cerebellar, autonomic and cord dysfunction. Cerebrospinal fluid was positive for GFAP autoantibody. Clinical improvement occurred after intravenous methylprednisolone and immunoglobulins. Conclusion(s): Although we are uncertain of a causal link of GFAP-A to mRNA vaccine, indirect activation of an underlying dysregulated immune milieu is plausible.Copyright © 2021 The Author(s)

Working Group for Myositis within the Swedish Rheumatism Association

The Swedish Rheumatism Association, our umbrella Organization: In Sweden, there are approximately one million people with different rheumatic diseases, and about 1400 of them have a myositis diagnosis. In addition to several local associations, there are 3 nationwide diagnostic groups for systemic inflammatory diseases: Working group for systemic lupus erythematosus (SLE), Working group for Systemic Sclerosis and Working group for Myositis. Goals and vision: We form opinion and influence politicians and decision-makers at all levels in issues that are important to us, such as access to rapid care and opportunities for rehabilitation. Knowledge and Education: We educate: * Representatives who can share knowledge based on their own experience and to provide support and help for people living with rheumatic disease. * Volunteers for patient schools. * Patient Research Partners since 2008. Research and fundings: : * We are the single largest private funder of Swedish rheumatology research. * Patient Research Partners should become obvious members in research projects. Working group for Myositis was established in 2020 and most of our activities have been on-line. The number of members is growing as we spread out the information. We will continue with our on-line events and together with our experts arrange our first patient conference in 2022. We are a member of the Swedish Rare Disease Association and European Network ERN ReCONNET. We have now three Patient Research Partners with myositis and we will continue to participate in international research projects, such as IMACS, Rehabilitation & exercise SIG. Our mission is to give support to myositis patients and their families, share knowledge of their disease, facilitate meeting with others with the same diagnosis for an exchange of experiences or just for fun. Our goals are to: * Inform through newsletters, patient meetings, website and webcasts. * Arrange lectures by myositis experts. * Arrange annual patient conference. * Raise awareness for the disease in society and inform healthcare professionals within primary care units. * Contribute to that all patients receives equally good care all over the country. * Inform about research results, ongoing studies and update information on new treatments and drugs. * Contribute to that all newly diagnosed patients have access to patient education and written information material about myositis. * Contribute for opportunities for rehabilitation, such as training in warm water pools and access to rehabilitation facilities in warm climate. * Collaborate with the Youth organization of the Swedish Rheumatism Association for Juvenile Dermatomyositis and provide support for parents, children and adolescents. * Collaborate with the myositis organizations in other countries. Our Webinars: The experts who have shared their knowledge on our webinars are: Ingrid Lundberg, Professor;Maryam Dastmalchi, MD, Rheumatologist;Helene Alexanderson, PhD, Associate professor, PT;Malin Regardt, PhD, OT;Balsam Hanna, Specialist Rheumatology;Dag Leonard, MD, Rheumatologist;Antonella Notarnicola, MD, Rheumatologist;Fabricio Espinosa, Rheumatologist, PhD candidate;Kristofer Andreasson, PT, PhD candidate;Jonatan Sjogren, OT;Lars Nordelv, CBT Therapist, also a patient;Helena Andersson, MD, Rheumatologist;Hanna Brauner, PhD, Dermatologist. Among the topics our webinars have covered so far are: Diagnostic criteria of myositis, new research findings, existing treatments and ongoing studies, Physical activity and its effects on depression, safety of high-intensity interval training, Occupational therapy, Patient Reported Outcomes, Myositis Associated Antibodies and how to deal with anxiety, cardiac involvement and osteoporosis in myositis, clinical findings and treatments for Antisynthetase syndrome skin involvement in Dermatomyositis, Covid-19 and vaccination.

Dutch Myositis Working Group (Dmwg)

Introduction. The poster of the Dutch Myositis Working Group (DMWG) aims to inform people about her goals, activities and ambitions. The group is run by seven patients, representing all types of myositis, supported by Spierziekten Nederland, the umbrella patient organization for neuromuscular disorders in The Netherlands and 4 myositis specialists as medical advisors. Chair: Ingrid de Groot. Contact email: myositis@spierziekten.nl Goals and ambitions of the Dutch myositis working group: * I n collaboration with medical advisors to provide information about IIM (idiopathic inflammatory myopathies) or myositis to newly diagnosed patients and their families: IIM types, symptoms, diagnosis, (new) treatment options, prognosis, inform them about the myositis expertise centres etc. * To connect and support people with all types of IIM: dermatomyositis (DM), polymyositis (PM), Anti Synthetase Syndrome (ASyS), immune mediated necrotizing myopathy (IMNM), juvenile dermatomyositis (JDM), overlap myositis. * To raise awareness of myositis among the public, health care professionals and researchers, pharmaceutical companies? * To collaborate with clinicians, researchers and funds on a national and international level with the aim to improve (clinical) care and research. * To stimulate and participate in the development and conducting of clinical trials. * To collaborate with myositis working groups and patient organisations abroad. * To represent the patient perspective within in the Myositis Network Netherlands and (inter)national myositis study groups. * Patient advocacy. Activities and services: * In person or online meetings aiming to offer moral support and an opportunity to share experiences, concerns etc. or just to socialize. Three times a year we organize separate meetings for people with IBM, for people with other IIM and for caregivers. * Website updates on treatment, guidelines, (inter)national research, activities and actualities (e.g. Covid situation). * Supply patients with brochures for GP/ family doctor, physiotherapist etc. * Online (secured) platform for members. * Annual patient conference with diagnosis specific scientific programs. * Monthly newsletters: these are personalized which means they contain mainly news on the receivers type of IIM (e.g. IBM or ASyS) and information on general topics concerning all people with IIM or neuromuscular disorder. * In person meetings and / or online webinars on general topics e.g. living with a chronic condition, work, pain, fatigue. * Annual meetings with medical advisors: the working group pays a visit to all medical advisors in their respective hospitals. * Representation at (inter)national conferences. * Representation in projects such as guidelines development. * Collaboration in (inter)national studies leading to enrolling Dutch patients, researchers and clinicians in multi-centre studies, (co-) authorships in publications and to presentations during conferences (Treat NMD, IMACS, MNN). * To advise and recommend on research proposals from patient perspective. * To advise decision makers on continuation of expert centres from patient perspective. Collaborations: * Myositis Network Netherlands: patient representation on the board. * OMERACT (Outcome Measures in Rheumatology): Patient Research Partner of the Myositis Working Group. * IMACS (International Myositis Assessment and Clinical Studies Group): steering committee member of Exercise & Rehabilitation Group, led by Helene Alexanderson, ass.prof PhD, RPT). * ENMC (European Neuromuscular Centre): patient representation in myositis workshops. * EULAR (European League against Rheumatism): member of PARE and Patient Research Partner. * GCOM. * ERN - NMD (European Reference Network for Neuromuscular Diseases): member of NMD working group led by em. prof. dr. Marianne de Visser. * Patient organizations for people living with myositis . We are in this together Since myositis is a (very) rare disease, the 'myositis community' is a small one although we're happy to say that it is expanding quite rapidly. Through our inte sive involvement in several national and international studies and research projects we now have close contacts with many myositis experts across the globe, which makes it easier to keep up with actualities and developments concerning research, treatment etc. and to disseminate this knowledge to our members. This helps us to inform, support and advocate for the Dutch people living with myositis and their families and at the same time it offers opportunities to give something back: by sharing with the research community and clinicians our experiential knowledge of the consequences of myositis on everyday life. That way we can contribute to more meaningful research. We can only go forward if we do this together! That is why we are very ambitious in our efforts to contribute to myositis research. Here we list our collaborative efforts: * In 2019 the Myositis Network Netherlands of clinicians and researchers with expertise in IIM was established in which the DMWG is representing the patient perspective by a member on the board. * In OMERACT Myositis Working Group a member of the DMWG is one of the two Patient Research Partners and as such an equal partner of this study aiming to define a set of core patient reported domains with regard to the quality of life and respective instruments for use in IIM. The involvement of the DMWG has led to the opportunity for Dutch patients to participate in Delphi surveys and to an opportunity for Dutch myositis clinics to collaborate in the longitudinal study that emerged from this. * The IMACS network is an important part of our international network. One of our DMWG members is member of the Executive Committee of the Exercise & Rehabilitation Group and as such can facilitate for Dutch patients to become involved in the current study with the ultimate objective to develop recommendations for exercise in all types of IIM. * Members of the DMWG participated in several ENMC workshops on IIM as patient representatives and will continue to do so in the future. * Through a PARE membership in EULAR and membership of the study group of 'collaborative research' the DMWG hopes to raise awareness of myositis within the influential EULAR community and to speak up on behalf of the patients in Europe living with IIM. * One of our members is member of the GCOM committee responsible for the patient program of GCOM and shares the ambitions of this GCOM committee to increase the involvement of patients in this very important IIM conference. * One DMWG member joined the ERN- Neuromuscular Disease group and as such represents the people with IIM living throughout Europe. * DMWG has ambitions to empower people living with IIM and to connect with them, crossing borders by doing so. We have close and amicable relationships with patient organisations in Australia, Czech Republic, Germany, Sweden, UK and USA. * Empowering patients is one of our goals and we accomplished this for instance in Sweden. On invitation by prof. dr. Ingrid Lundberg our chair visited the Karolinska Institute, spent a week with their myositis team and in return was one of the speakers on the annual patient meeting and helped the Swedish patients establish their own myositis working group.

The effect of the COVID-19 pandemic on US Food and Drug Administration-funded clinical trials and natural history studies for rare diseases.

BACKGROUND: Since 1983, the Orphan Product Grants Program, administered by the US Food and Drug Administration, provides funding for clinical trials and natural history studies in rare diseases. The COVID-19 pandemic created new challenges in rare disease product development. This study sought to determine the effects of the pandemic on rare disease studies using data from grantees of this program, and determine lessons learned that can potentially be applied to future trials in rare diseases. METHODS: All grants that were being funded by the Orphan Products Grants Program between March 2020 and March 2021 were included in the study. Data was gathered from grantees and described the effects of the pandemic on multiple aspects of the studies including enrollment, patient follow-up, protocol, and budget. RESULTS: There were 62 grants active during the study period, and of these 54 (87%) were clinical trials and 8 (13%) were natural history studies. 94% of the grantees reported their studies being affected by the COVID-19 pandemic, and the addition of virtual capabilities was reported by 34 (55%) of grantees. CONCLUSIONS: This study suggested two important lessons learned. First, virtual capabilities, when appropriate, can be an important component of trials because they decrease the travel burden on participants and reduce in-person risks, which should increase patient recruitment and retention. Second, building in flexibility in clinical trials is critical in the post-COVID era and could include increasing the use of multi-site trials, clinical networks, and innovative designs and collaborations to speed up trials without compromising study data.

Impact of the Covid-19 epidemic on a US sample of patients with myasthenia gravis.

Introduction: The Covid-19 pandemic has devastated the world and demonstrated the inadequacy of health care in the United States. To assess its impact, the Rare Disease Clinical Research Network conducted a survey to assess the pandemic on the rare disease community of patients, including those with myasthenia gravis (MG). Methods: A cross-sectional survey was designed to target people or their care givers who live in the United States, have a rare disease, and are under 90 years of age. Respondents logged onto a dedicated web page and completed the survey online, which requested demographic, disease-specific, drug treatment, and symptom information as well as assessment of Covid-19 impact on them. The survey was open from May 2020 to December 2020. Results: Five hundred ninety-four with self-reported myasthenia gravis completed the survey, which was the largest number of respondents. Sixty percent of respondents were women with a mean age of 60 years. Eighty-nine percent identified as White. Respondents did not appreciate a worsening of symptoms after the pandemic. Only 7 respondents reported the diagnosis of Covid-19 but 11% indicated they had difficulty accessing care at the time of the survey. Discussion and Conclusion: Patients with MG complained of worse access to medical care during the early months of the pandemic, including challenges in diagnosis of suspected Covid-19 infection. A major limitation of the survey is its inability to access minority populations. Nevertheless, the results of the Rare Disease Clinical Research Network (RCDRN) survey of patients with MG provide clear evidence that the pandemic has demonstrated the deficiencies in US healthcare.

Impact of Covid-19 Pandemic on Patients with Myasthenia Gravis Deeper understanding of the consequences of the Covid-19 pandemic on people with rare diseases is critically important in order to enhance health care in the future. The Rare Disease Clinical Research Network (RDCRN) performed a web-based survey of individuals with rare diseases in the first year of the pandemic utilizing questions to assess the impact of the pandemic on their symptoms, access to healthcare, and medication use. Five hundred and ninety-four respondents reported having myasthenia gravis (MG). The average age was 60 years and 60% were women. Nearly ninety percent were White. A large minority indicated difficulty accessing health care and nearly a third used telemedicine. Only seven respondents indicated a diagnosis of Covid-19 but many more had symptoms consistent with infection. Overall, there was no increase in symptoms of MG after the beginning of the pandemic. The pandemic has demonstrated the deficiencies in US healthcare, and these are appreciated in the results of the RCDRN survey of patients with MG. The RDCRN will continue to survey the rare disease community to understand the ongoing impact of the Covid-19 pandemic.

Decentralized clinical trials and rare diseases: a Drug Information Association Innovative Design Scientific Working Group (DIA-IDSWG) perspective.

BACKGROUND: Traditional clinical trials require tests and procedures that are administered in centralized clinical research sites, which are beyond the standard of care that patients receive for their rare and chronic diseases. The limited number of rare disease patients scattered around the world makes it particularly challenging to recruit participants and conduct these traditional clinical trials. MAIN BODY: Participating in clinical research can be burdensome, especially for children, the elderly, physically and cognitively impaired individuals who require transportation and caregiver assistance, or patients who live in remote locations or cannot afford transportation. In recent years, there is an increasing need to consider Decentralized Clinical Trials (DCT) as a participant-centric approach that uses new technologies and innovative procedures for interaction with participants in the comfort of their home. CONCLUSION: This paper discusses the planning and conduct of DCTs, which can increase the quality of trials with a specific focus on rare diseases.