Victoria Johnson joined the MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and now HCPLive. You can reach her at vjohnson@mjhlifesciences.com

Victoria Johnson

ClASsification criteria for Psoriatic ARthritis (CASPAR) identified more patients with 

 (PsA) than International League of Associations for Rheumatology (ILAR) criteria in peoplewith juvenile idiopathic arthritis (JIA), demonstrating its potential utility.

Lead investigator Agnes Szentpetery, MD, PhD, Uppsala University and Uppsala University Hospital, Uppsala, Sweden, and colleagues assessed the clinical characteristics of patients with JIA from defined geographic regions of Denmark, Finland, Norway, and Sweden with disease onset from 1997 to 2000 that were enrolled prospectively and followed up for 18 years. Patients were classified according to the ILAR criteria at baseline, and they applied ILAR and CASPAR criteria at 18 years.

“Classifying patients with JPsA is often challenging because, in contrast to adult PsA, psoriasis may manifest up to 10 years after arthritis onset in children and may be prevented by the use of disease-modifying antirheumatic drugs,” Szentpetery and colleagues wrote.

 “...The objectives of our study were to assess the clinical characteristics of patients with JIA who fulfill the CASPAR criteria as young adults 18 years after disease onset in a population-based setting and to identify features likely to predict PsA, including characteristics related to juvenile PsA and family history of psoriasis.”

Among the 510 patients enrolled in the study, 434 participated in the 18-year follow-up. Szentpetery and colleagues found that 28 (6.5%) met the ILAR criteria, and 41 (9.4%) fulfilled the CASPAR criteria. Patients with wrist or subtalar joint involvement at onset were more likely to be classified with PsA at 18 years (odds ratio [OR], 3.3; 

 = .01, respectively). The investigators also found that presence of psoriasis (OR, 20.2; P < .001), nail abnormalities (OR 11.6; 

 < .001) were significantly associated with PsA development.1

“Our study is a contribution to the ongoing debate about the classification and rationale of JPsA and highlights the importance of early recognition of features associated with PsA. Further studies on the utility of the CASPAR criteria in patients with JIA are needed to potentially recognize more patients with JPsA early in the disease course and ultimately to provide better care and more favorable long-term outcome for children with JPsA,” Szentpetery and colleagues concluded.

Other recent research in JIA was presented at November’s 

can College of Rheumatology (ACR) Convergence 2024

in Washington, DC. One such study evaluated tofacitinib in a double-blind study compared to placebo and found no evidence of superiority. However, the phase 3, randomized, withdrawal study (NCT03000439) did find evidence of improvements in its open-label study phase.

“What we did see is that the medication was well tolerated, and based on the OL part, it has, in my mind, at least some therapeutic benefit for a subset of patients with sJIA,” lead investigator Hermine Brunner, MD, MDc, MBA, Director, Division of Rheumatology, and professor, Department of Pediatrics, Cincinnati Children’s told 

Szentpetery A, Glerup M, Aalto K, et al. Characteristics That Predict Psoriatic Arthritis by the Classification Criteria for Psoriatic Arthritis in Patients With Juvenile Idiopathic Arthritis 18 Years After Disease Onset. 

 Published online December 10, 2024. Doi.org/10.1002/acr2.11758

Brunne H, Li C, Chinniah K, et al. Efficacy and Safety of Tofacitinib in Patients with Active Systemic Juvenile Idiopathic Arthritis. Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract L09.

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The CASPAR criteria identified more patients with psoriatic arthritis (PsA) in juvenile idiopathic arthritis (JIA) cases than the ILAR criteria, suggesting its potential utility. A study led by Agnes Szentpetery assessed JIA patients from Nordic countries over 18 years, finding that wrist or subtalar joint involvement, psoriasis, nail abnormalities, and dactylitis were significant predictors of PsA. The study emphasizes the importance of early recognition of PsA features. Additionally, a study on tofacitinib for systemic JIA showed some therapeutic benefits in an open-label phase.

A prospective study also found that the presence of psoriasis and dactylitis at disease onset were the strongest predictors for the development of PsA. 

CASPAR Criteria May Identify More Patients With Juvenile PsA Than ILAR Criteria 

Davidow discussed how a new cohort study has helped support findings of an older European study and the need for a prospective trial to confirm the increased risk.

Kimberly A. Davidow, MD: Elucidating Risk of Autoimmune Disease in Childhood Cancer Survivors

A new, real-world cohort study has further identified an increased risk of autoimmune disease in childhood cancer survivors after an initial Scandinavian cohort study suggested this increased risk.

Findings from the study were presented at the

 66th American Society of Hematology (ASH) Annual Meeting and Exposition

, held December 7-10, 2024, in San Diego, California, by Kimberly A. Davidow, MD, pediatric hematology/oncology, Nemours Children’s Health.

“With the increased availability of these different kinds of large data platforms, Jefferson [Health] had access to Trinetics, which pulls in a large amount of healthcare data, and [they] wanted to use that to try to look at autoimmune diseases and try to cancer survivors,” Davidow told 

Although limited by constraints inherent to many electronic healthcare records, Davidow and colleagues found that childhood cancer survivors had an increased risk of rheumatoid arthritis, Sjogren disease, ulcerative colitis, and Crohn disease. Davidow shared that these associations should be looked further into in prospective trials, and primary care providers should keep in mind these increased risks when treating adult childhood cancer survivors.

“If you are a primary care provider who's taking care of someone who's a childhood cancer survivor, there's a lot of things you need to know, but this is also important to know. If they're starting to have complaints about joint pains or unusual rashes that, in another patient who didn't have this history, you might not think much of it yet, you need to think more about it for them, because there is this increased risk, and so you should screen sooner than you might for someone else,” Davidow stressed.A new, real-world cohort study has further identified an increased risk of autoimmune disease in childhood cancer survivors after an initial Scandinavian cohort study suggested this increased risk.

“If you are a primary care provider who's taking care of someone who's a childhood cancer survivor, there's a lot of things you need to know, but this is also important to know. If they're starting to have complaints about joint pains or unusual rashes that, in another patient who didn't have this history, you might not think much of it yet, you need to think more about it for them, because there is this increased risk, and so you should screen sooner than you might for someone else,” Davidow stressed.

Davidow KA, Rohan TZ, Roslund CR, et al. Real-World Data Shows Increased Incidence of Autoimmune Disease in Survivors of Childhood Lymphoid Malignancies. Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 5094

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The FDA has approved Humacyte’s acellular tissue engineered vessel-tyod (ATEV) therapy, under the name Symvess, for use in adults as a vascular conduit for extremity arterial injury when urgent revascularization is needed to avoid imminent limb loss, and when autologous vein graft is not feasible.

“Today’s approval provides an important additional treatment option for individuals with vascular trauma, produced using advanced tissue engineering technology,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research (CBER), said in a statement.

“The FDA remains committed to facilitating the development of innovative products that offer potentially life-saving benefits for patients with severe injuries.”

The therapy is indicated to help provide revascularization when autologous vein grafting or implantation of a synthetic graft is not feasible. The ATEV is composed of human extracellular matrix (ECM) proteins typically found in human blood vessels and is a sterile, acellular tissue engineered vessel. Human vascular smooth muscle cells derived from human aortic tissue are utilized in the ATEV’s tissue engineering process.

“Currently available treatment options are limited for vascular trauma, which can lead to severe and potentially life-threatening complications,” Nicole Verdun, MD, director of the Office of Therapeutic Products in CBER, added.

“Today’s decision to approve a new therapeutic product based on novel medical technology represents important progress in addressing a significant unmet medical need.”

The ATEV was approved based on data from the pivotal Phase 2/3, prospective, single arm, multicenter V005 study in patients with life- or limb-threatening vascular trauma, as well as real-world evidence from the treatment of wartime injuries in Ukraine under a humanitarian aid program.

In the study, 54 patients received the ATEV to repair an arterial vessel in the extremity. Of these patients, 36 (67%) retained primary patency (blood flow present without any intervention) and 39 (72%) retained secondary patency (at least one intervention required to maintain blood flow) at day 30. Within the first 30 days, 5 patients (9%) underwent amputation of the treated limb, and by the end of the study at month 36, 8 (15%) patients underwent amputation of the treated limb.

The ATEV has been used to repair traumatic injuries including car accidents, gunshot wounds, blast wounds, and industrial accidents by vascular and trauma surgeons in Level 1 Trauma centers throughout the United States, Israel, and Ukraine, with high rates of patency, or blood flow, and low rates of amputation and infection. These findings were published in 

“The approval of a vascular conduit that resists infection and remodels into native arteries is an extraordinary technological advancement that will have a huge impact on the quality of trauma care around the world,” investigator Charles J. Fox, MD, FACS, Director of Vascular Surgery, University of Maryland Capital Region, said in a statement.

“SYMVESS is perfectly sized to treat most injuries, has excellent handling properties, and reduces time necessary to save both life and limbs. The Humacyte team has responsibly and scientifically solved a major clinical problem that I believe will reduce the amputation rate for traumatic vascular injury. They should be congratulated on an accomplishment that will undoubtedly advance our specialty to the next level.”

Common adverse events (AEs) include thrombosis, fever, pain, and anastomotic stenosis. Serious AEs that may occur include graft rupture, anastomotic failure and thrombosis. Transmission of infectious diseases or infectious agents can occur from the human donor cells and human and bovine reagents used in manufacturing the ATEV, although donor eligibility requirements are in place to prevent the transmission of infectious diseases.

“The FDA approval of SYMVESS will make it the preferred conduit for complex vascular injuries, and particularly those at risk for infection,” investigator Ernest E. Moore, MD, FACS, Director of Research, Ernest E. Moore Shock Trauma Center at Denver Health, added.

“I look forward to using SYMVESS in my practice.”

The ATEV previously also received Priority Review and Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA, and is also designated as a Priority Product by the U.S. Department of Defense, which allowed expedited development under Public Law 115-92 for a product that may diagnose, treat or prevent serious or life-threatening diseases or conditions facing American military personnel.

REFERENCES
1. FDA Approves First Acellular Tissue Engineered Vessel to Treat Vascular Trauma in Extremities. News release. FDA. December 20, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-acellular-tissue-engineered-vessel-treat-vascular-trauma-extremities#

2. Humacyte Announces FDA Approval of SYMVESS™ (acellular tissue engineered vessel-tyod) for the Treatment of Extremity Vascular Trauma. News release. Humacyte. December 19, 2024. https://uk.finance.yahoo.com/news/humacyte-announces-fda-approval-symvess-034700671.html

3. Moore EE, Curi M, Namias N, et al. Bioengineered Human Arteries for the Repair of Vascular Injuries. JAMA Surg. Published online November 20, 2024. doi:10.1001/jamasurg.2024.4893

The FDA has approved Humacyte's acellular tissue engineered vessel (ATEV) therapy, Symvess, for urgent revascularization in extremity arterial injuries when autologous vein grafts are not feasible. This approval is based on data from a pivotal Phase 2/3 study and real-world evidence from wartime injuries. Symvess, composed of human extracellular matrix proteins, has shown high patency rates and low amputation rates. It is recognized for its infection resistance and ability to remodel into native arteries, offering a significant advancement in trauma care.

The ATEV therapy, named Symvess, provides revascularization when autologous vein graft or implantation of a synthetic graft is not feasible. 

FDA Approves First Acellular Tissue Vessel Therapy for Extremity Vascular Trauma  

 in patients with gout initiating urate-lowering therapy compared to those not prescribed prophylactic colchicine.

Lead investigator Edoardo Cipolletta, MD, Academic Rheumatology, School of Medicine, Nottingham City Hospital, University of Nottingham, United Kingdom, and colleagues conducted a retrospective new-user cohort study using data from the Clinical Practice Research Datalink Aurum, an English primary-care database linked to hospitalization and mortality records. The study included people with gout initiating urate-lowering therapy for the first time and compared people prescribed flare prophylaxis with colchicine with those not prescribed any gout flare prophylaxis.

“Cipolletta and colleagues propose the prevention of gout flare as an additional cause of the beneficial effect of colchicine on cardiovascular event risk. Gout flares have been associated with an increase in cardiovascular events, albeit transient, following flare. One can speculate whether this effect is additional to or part of a more general colchicine effect on the chronic inflammatory state that is supposedly present in all patients with gout, also between flares,” Hein Janssens, MD, PhD, Department of Primary and Community Care, Radboudumc Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen 6500, Netherlands, and Matthijs Janssen, MD, PhD, Department of Rheumatology, VieCuri Medical Centre, Venlo, Netherlands, wrote in a related editorial.

 “This gout inflammatory state has been suggested to have a link with increased cardiovascular event risks similar to rheumatoid arthritis and in accordance with circulating proinflammatory cytokines associated with monosodium urate crystal depositions and cardiovascular events.”

Cipoletta and colleagues included 99,800 patients with gout initiating urate-lowering therapy in the study, 25,511 (25.6%) of which were female and 84,928 (85.1%) of which were White. Participants had a mean age of 62.8 years (standard deviation [SD], 15.5), 4063 (4.1%) patients had previous cardiovascular events and 16,028 (16.1%) were prescribed colchicine prophylaxis.

The investigators found that patients prescribed colchicine prophylaxis had a significantly lower risk of cardiovascular events compared with those without, with weighted rates of cardiovascular events of 28.8 per 1000 person-years (95% CI, 25.2-33.2) and 35.3 per 1000 person-years (95% CI, 33.0-37.9), respectively. These rates translate to a weighted rate difference of –6·5 [95% CI, –9·4 to –3·6] per 1000 person-years and a weighted hazard ratio of 0.82 [95% CI, 0.69–0.94] in patients with prophylactic colchicine in the intent-to-treat analysis. These findings were supported by further, stratified analyses, and for secondary outcomes.

“Let the findings in this robust, high-quality observational study be the invitation for gout researchers to design a randomized controlled trial to confirm them. After all, the observed beneficial effect of colchicine concerns a huge group of patients worldwide,” Janssens and Janssen wrote.

 “In addition, it is conceivable that, if a cardiovascular risk reduction is indeed confirmed, a strong argument arises to recommend the prescription of a course of colchicine to all (flaring) patients with gout, independently of their preference for urate-lowering therapy in general or urate-lowering therapy with or without colchicine prophylaxis more specifically.”

REFERENCES
1. Cipoletta E, Nakafero G, McCormick N, et al. Cardiovascular events in patients with gout initiating urate-lowering therapy with or without colchicine for flare prophylaxis: a retrospective new-user cohort study using linked primary care, hospitalisation, and mortality data. 

 Published online December 18, 2024. doi: 10.1016/S2665-9913(24)00248-0

2. Janssens H, Janssen M. Beneficial side-effects of colchicine for patients with gout. 

Prophylactic colchicine significantly reduces cardiovascular event risk in gout patients starting urate-lowering therapy. A retrospective cohort study analyzed data from the Clinical Practice Research Datalink Aurum, involving 99,800 patients. Those prescribed colchicine had a lower cardiovascular event rate compared to those without. The study suggests that colchicine's benefits may extend beyond flare prevention, potentially impacting the chronic inflammatory state in gout. The findings advocate for further randomized controlled trials to confirm colchicine's cardiovascular benefits and recommend its use in gout management.

These findings, from an observational study, should be confirmed in a randomized, controlled trial.