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Article ; Online: Recent advances in the treatment of giant cell arteritis.

Springer, Jason M / Kermani, Tanaz A

Best practice & research. Clinical rheumatology

2023 Volume 37, Issue 1, Page(s) 101830

Abstract: Giant cell arteritis (GCA) is a systemic, granulomatous, large-vessel vasculitis that affects individuals over the age of 50 years. Morbidity from disease includes cranial manifestations which can cause irreversible blindness, while extra-cranial ... ...

Abstract	Giant cell arteritis (GCA) is a systemic, granulomatous, large-vessel vasculitis that affects individuals over the age of 50 years. Morbidity from disease includes cranial manifestations which can cause irreversible blindness, while extra-cranial manifestations can cause vascular damage with large-artery stenosis, occlusions, aortitis, aneurysms, and dissections. Glucocorticoids while efficacious are associated with significant adverse effects. Furthermore, despite treatment with glucocorticoids, relapses are common. An understanding of the pathogenesis of GCA has led to the discovery of tocilizumab as an efficacious steroid-sparing therapy while additional therapeutic targets affecting different inflammatory pathways are under investigation. Surgical treatment may be indicated in cases of refractory ischemia or aortic complications but data on surgical outcomes are limited. Despite the recent advances, many unmet needs exist, including the identification of patients or subsets of GCA who would benefit from earlier initiation of adjunctive therapies, patients who may warrant long-term immunosuppression and medications that sustain permanent remission. The impact of medications like tocilizumab on long-term outcomes, including the development of aortic aneurysms and vascular damage also warrants investigation.
MeSH term(s)	Humans ; Middle Aged ; Giant Cell Arteritis/drug therapy ; Glucocorticoids/therapeutic use
Chemical Substances	Glucocorticoids
Language	English
Publishing date	2023-06-14
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2052323-3
ISSN	1532-1770 ; 1521-6942
ISSN (online)	1532-1770
ISSN	1521-6942
DOI	10.1016/j.berh.2023.101830
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Article ; Online: Polyarteritis nodosa: an evolving primary systemic vasculitis.

Springer, Jason M / Byram, Kevin

Postgraduate medicine

2022 Volume 135, Issue sup1, Page(s) 61–68

Abstract: Polyarteritis nodosa (PAN) is a primary form of vasculitis characterized by inflammation of primarily medium-sized arteries. Several key events have shaped the current spectrum of the disease including the separation of a subgroup with microscopic ... ...

Abstract	Polyarteritis nodosa (PAN) is a primary form of vasculitis characterized by inflammation of primarily medium-sized arteries. Several key events have shaped the current spectrum of the disease including the separation of a subgroup with microscopic polyangiitis, the discovery of the association of hepatitis B, and the discovery of adenosine deaminase 2 deficiency (DADA2). With the discovery of secondary causes of PAN and changing nomenclature, the incidence of PAN has declined over time. Common manifestations include constitutional symptoms, skin involvement, peripheral neuropathy, gastrointestinal disease, and renal involvement. DADA2 is a genetic cause of medium vessel vasculitis that is important to distinguish from primary PAN as treatment with TNF inhibitors can prevent morbidity and mortality in those with a vasculitis phenotype. Treatment of systemic primary PAN involves the use of systemic immunosuppressive therapy largely guided by the severity of disease. With current treatment regimens, the prognosis has changed from a once uniformly fatal disease to a 5-year survival rate above 80%.
MeSH term(s)	Humans ; Polyarteritis Nodosa/diagnosis ; Polyarteritis Nodosa/drug therapy ; Polyarteritis Nodosa/etiology ; Adenosine Deaminase/genetics ; Intercellular Signaling Peptides and Proteins ; Vasculitis/complications ; Prognosis
Chemical Substances	Adenosine Deaminase (EC 3.5.4.4) ; Intercellular Signaling Peptides and Proteins
Language	English
Publishing date	2022-06-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	410138-8
ISSN	1941-9260 ; 0032-5481
ISSN (online)	1941-9260
ISSN	0032-5481
DOI	10.1080/00325481.2022.2088940
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Article ; Online: Vasculitis Mimics and Other Related Conditions.

Springer, Jason M / Villa-Forte, Alexandra

Rheumatic diseases clinics of North America

2023 Volume 49, Issue 3, Page(s) 617–631

Abstract: The approach to diagnosis of primary systemic vasculitis can be challenging, often requiring consideration of important secondary causes of vasculitis and non-inflammatory mimics. An atypical pattern of vascular involvement and/or atypical features of ... ...

Abstract	The approach to diagnosis of primary systemic vasculitis can be challenging, often requiring consideration of important secondary causes of vasculitis and non-inflammatory mimics. An atypical pattern of vascular involvement and/or atypical features of primary vasculitis (eg, cytopenia, lymphadenopathy) should prompt a more thorough investigation into other diseases. Herein, we review selected mimics organized by the size of blood vessels typically affected.
MeSH term(s)	Humans ; Vasculitis/diagnosis
Language	English
Publishing date	2023-04-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	92118-x
ISSN	1558-3163 ; 0889-857X
ISSN (online)	1558-3163
ISSN	0889-857X
DOI	10.1016/j.rdc.2023.03.008
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Article: The Past, Present, and Future of Equine Science.

White-Springer, Sarah H / Bruemmer, Jason / Coleman, Robert J

Journal of equine veterinary science

2023 Volume 124, Page(s) 104297

Abstract: A core group of 27 equine nutritionists and physiologists joined together in the late 1960s to formally address and enhance the direction of equine research, creating the Equine Nutrition and Physiology Society. In 2003, that growing society transformed ... ...

Abstract	A core group of 27 equine nutritionists and physiologists joined together in the late 1960s to formally address and enhance the direction of equine research, creating the Equine Nutrition and Physiology Society. In 2003, that growing society transformed into the Equine Science Society, which now serves as the preeminent, internationally recognized scientific equine organization. In recent years, it has been appreciated that equine science encompasses a wide range of focus areas, including exercise science, nutrition, genetics, reproductive physiology, teaching and extension, production and management, and mix of other specialties, qualified as biosciences. Additionally, trainees are highly valued in the society, with the clear understanding that young people are the future of equine science. Amongst tightening budgets, equine researchers must focus on timely dissemination of high-quality research studies and development of strong, interdisciplinary, cross-species, and multi-institutional collaborations to ensure sustainability of academic research programs. With a little creativity, equine science will continue to thrive for the betterment of the horse and all involved in the equine industry.
MeSH term(s)	Animals ; Horses ; Veterinary Medicine/trends
Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2102631-2
ISSN	1542-7412 ; 0737-0806
ISSN (online)	1542-7412
ISSN	0737-0806
DOI	10.1016/j.jevs.2023.104297
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Article ; Online: Molecular Evidence for Relaxed Selection on the Enamel Genes of Toothed Whales (Odontoceti) with Degenerative Enamel Phenotypes.

Randall, Jason G / Gatesy, John / McGowen, Michael R / Springer, Mark S

Genes

2024 Volume 15, Issue 2

Abstract: Different species of toothed whales (Odontoceti) exhibit a variety of tooth forms and enamel types. Some odontocetes have highly prismatic enamel with Hunter-Schreger bands, whereas enamel is vestigial or entirely lacking in other species. Different ... ...

Abstract	Different species of toothed whales (Odontoceti) exhibit a variety of tooth forms and enamel types. Some odontocetes have highly prismatic enamel with Hunter-Schreger bands, whereas enamel is vestigial or entirely lacking in other species. Different tooth forms and enamel types are associated with alternate feeding strategies that range from biting and grasping prey with teeth in most oceanic and river dolphins to the suction feeding of softer prey items without the use of teeth in many beaked whales. At the molecular level, previous studies have documented inactivating mutations in the enamel-specific genes of some odontocete species that lack complex enamel. At a broader scale, however, it is unclear whether enamel complexity across the full diversity of extant Odontoceti correlates with the relative strength of purifying selection on enamel-specific genes. Here, we employ sequence alignments for seven enamel-specific genes (
MeSH term(s)	Humans ; Animals ; Phylogeny ; Whales/genetics ; Dolphins/genetics ; Sequence Alignment ; Dental Enamel
Language	English
Publishing date	2024-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes15020228
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Article: Dose-dependent Pharmacological Response to Rituximab in the Treatment of Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

Springer, Jason M / Funk, Ryan S

The Journal of rheumatology

2021 Volume 48, Issue 11, Page(s) 1718–1724

Abstract: Objective: Rituximab (RTX) is effective in the induction and maintenance of remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, uncertainty remains regarding the optimal maintenance dosing regimen. This work ... ...

Abstract	Objective: Rituximab (RTX) is effective in the induction and maintenance of remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, uncertainty remains regarding the optimal maintenance dosing regimen. This work evaluates the relationship between variability in RTX dosing and pharmacological response in AAV. Methods: A prospective cohort of patients with AAV (n = 28) with either granulomatosis with polyangiitis (n = 23) or microscopic polyangiitis (n = 5) receiving maintenance RTX therapy were followed in a single tertiary care academic medical center over a 2-year period. Patient demographics, RTX dosing information, and trough plasma RTX levels were collected along with laboratory measures of pharmacologic response, including B cell counts and ANCA titers. Results: RTX dosing information from 94 infusions with 59 trough samples were collected with a mean ± SD dose of 640 ± 221 mg, dosing interval of 210 ± 88 days, and trough plasma RTX concentration of 622 ± 548 ng/mL. RTX trough concentrations were associated with RTX dose (ρ = 0.60, Conclusion: RTX maintenance dosing of 500 mg every 6 months may be inadequate to maintain B cell depletion in the treatment of AAV.
MeSH term(s)	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy ; Antibodies, Antineutrophil Cytoplasmic ; Humans ; Prospective Studies ; Remission Induction ; Rituximab/therapeutic use ; Treatment Outcome
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2021-08-01
Publishing country	Canada
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
DOI	10.3899/jrheum.210361
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Article ; Online: VEXAS-Defining UBA1 Somatic Variants in 245,368 Diverse Individuals in the NIH All Of Us Cohort.

Corty, Robert W / Brogan, James / Byram, Kevin / Springer, Jason / Grayson, Peter C / Bick, Alexander G

Arthritis & rheumatology (Hoboken, N.J.)

2024

Abstract: Objective: Somatic variants in UBA1 cause VEXAS, a recently described, systemic autoinflammatory disease. Research on VEXAS has largely focused on highly symptomatic patients. We sought to determine the prevalence of canonical, VEXAS-associated somatic ... ...

Abstract	Objective: Somatic variants in UBA1 cause VEXAS, a recently described, systemic autoinflammatory disease. Research on VEXAS has largely focused on highly symptomatic patients. We sought to determine the prevalence of canonical, VEXAS-associated somatic variants and their disease penetrance in a diverse, unselected population. Methods: We analyzed clinical-grade whole genome sequencing data from 245,368 participants in the All of Us Research Program. We compared persons carrying a canonical VEXAS-associated somatic variant to age, sex, and ancestry matched controls across the domains of diagnoses, medications, and laboratory values. Results: 74 participants were identified who carry one VEXAS-defining somatic variant, UBA1 c.121A>C, p.Met41Leu. The variant allele fraction ranged from 4.5% to 33%. No other canonical VEXAS-associated variants were identified. Of the 74 carriers, 62 (84%) were women, 20 (27%) were African American, and 14 (19%) were American Admixed/Latino. There was no statistically significant association between case/control status and any VEXAS-associated diagnosis code, medication prescription, or laboratory value. Conclusion: We report the largest cohort to date of persons with the VEXAS-associated p.Met41Leu somatic variant. This cohort differed substantially from reported cohorts of patients with clinical VEXAS, having a higher proportion of persons who were young, female, and of diverse ancestry. Variant allele fractions were lower than reported in clinical VEXAS cohorts, and bioinformatic analysis detected no clinical manifestations of VEXAS. Thus, the UBA1 p.Met41Leu somatic variant displayed incomplete penetrance for VEXAS. Further study is needed to determine the natural history of VEXAS-associated somatic variants in the predisease phase.
Language	English
Publishing date	2024-01-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.42802
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Article ; Online: Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial.

Geetha, Duvuru / Dua, Anisha / Yue, Huibin / Springer, Jason / Salvarani, Carlo / Jayne, David / Merkel, Peter

Annals of the rheumatic diseases

2024 Volume 83, Issue 2, Page(s) 223–232

Abstract: Objectives: To evaluate the efficacy and safety of avacopan in the subgroup of patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis receiving background induction therapy with rituximab in the phase 3 ADVOCATE trial.: ... ...

Abstract	Objectives: To evaluate the efficacy and safety of avacopan in the subgroup of patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis receiving background induction therapy with rituximab in the phase 3 ADVOCATE trial. Methods: Key efficacy outcomes were remission at week 26 and sustained remission at week 52. Additional outcomes included the Glucocorticoid Toxicity Index, estimated glomerular filtration rate, urinary albumin to creatinine ratio, health-related quality of life and safety. Results: Of the 330 patients who received study medication, 214 (64.8%) received rituximab (once weekly for 4 weeks), with a mean age of 59.8 years; 163 (76.2%) had renal vasculitis and 125 (58.4%) were newly diagnosed. Remission at week 26 and sustained remission at week 52 were achieved by 83/107 (77.6%) and 76/107 (71.0%) patients in the avacopan group and 81/107 (75.7%) and 60/107 (56.1%) in the prednisone taper group, respectively. The relapse rate, recovery of renal function, speed of reduction in albuminuria and glucocorticoid toxicity favoured the avacopan group. Serious adverse events occurred in 34.6% and 39.3% of patients in the avacopan and prednisone taper groups, respectively. Conclusions: These data suggest that in patients with ANCA-associated vasculitis receiving rituximab, efficacy of treatment with avacopan compared with a prednisone taper was similar at week 26 and greater at week 52, with a favourable safety profile. In addition, avacopan was associated with improved renal outcomes and lower glucocorticoid toxicity. These results demonstrate the efficacy and safety of avacopan in patients receiving background induction therapy with rituximab. Trial registration number: NCT02994927.
MeSH term(s)	Humans ; Middle Aged ; Rituximab/adverse effects ; Immunosuppressive Agents/therapeutic use ; Prednisone ; Glucocorticoids/adverse effects ; Quality of Life ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy ; Remission Induction ; Antibodies, Antineutrophil Cytoplasmic ; Aniline Compounds ; Nipecotic Acids
Chemical Substances	Rituximab (4F4X42SYQ6) ; Immunosuppressive Agents ; avacopan (O880NM097T) ; Prednisone (VB0R961HZT) ; Glucocorticoids ; Antibodies, Antineutrophil Cytoplasmic ; Aniline Compounds ; Nipecotic Acids
Language	English
Publishing date	2024-01-11
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/ard-2023-224816
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Article ; Online: Update on the Treatment of Giant Cell Arteritis and Polymyalgia Rheumatica.

El Chami, Sarah / Springer, Jason M

Rheumatic diseases clinics of North America

2022 Volume 48, Issue 2, Page(s) 493–506

Abstract: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are considered 2 diseases on the same spectrum due to their many underlying similarities. In recent years, both diseases have witnessed both diagnostic and treatment advances, which shaped the ... ...

Abstract	Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are considered 2 diseases on the same spectrum due to their many underlying similarities. In recent years, both diseases have witnessed both diagnostic and treatment advances, which shaped the way we manage them. In this article, the authors focus on different diagnostic modalities in GCA as well as the presence of different clinical phenotypes and the role of screening for aortic involvement. The authors also discuss traditional treatments and the role of evolving steroid-sparing agents in the management of both GCA and PMR.
MeSH term(s)	Giant Cell Arteritis/diagnosis ; Giant Cell Arteritis/drug therapy ; Glucocorticoids/therapeutic use ; Humans ; Polymyalgia Rheumatica/diagnosis ; Polymyalgia Rheumatica/drug therapy
Chemical Substances	Glucocorticoids
Language	English
Publishing date	2022-05-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	92118-x
ISSN	1558-3163 ; 0889-857X
ISSN (online)	1558-3163
ISSN	0889-857X
DOI	10.1016/j.rdc.2022.02.007
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Article ; Online: Defining a Therapeutic Window for Rituximab Maintenance Therapy in ANCA-Associated Vasculitis: A Longitudinal Observational Study.

Springer, Jason Michael / Funk, Ryan S

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

2020 Volume 27, Issue 5, Page(s) 215–217

MeSH term(s)	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy ; Antibodies, Antineutrophil Cytoplasmic ; Humans ; Longitudinal Studies ; Remission Induction ; Rituximab
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2020-12-15
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	1283266-2
ISSN	1536-7355 ; 1076-1608
ISSN (online)	1536-7355
ISSN	1076-1608
DOI	10.1097/RHU.0000000000001688
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