Rheumatic Diseases CE/CME ACCREDITED Watch Time: 49 mins

touchSATELLITE SYMPOSIUM IgG4-related disease: How to identify, diagnose and treat

Watch leading experts discuss the clinical presentation, pathogenesis and diagnosis of immunoglobulin G4-related disease (IgG4-RD), and review current and emerging treatment strategies.

Prof. John Stone

Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA

CHAIR

Panelists:
Dr Emanuel Della Torre, Dr Arezou Khosroshahi
Watch Time: 02:59

Prof. John Stone introduces this touchSATELLITE SYMPOSIUM on how to identify, diagnose and treat IgG4-RD that was recorded at the ACR Convergence 2023.

 
Watch Time: 10:44

Prof. John Stone discusses the pathophysiology of IgG4-RD and reviews the clinical presentation and typical organ involvement of this rare immune-mediated condition.

Tutorial

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Poll

What are the main challenges in identifying IgG4-RD?

IgG4-RD, immunoglobulin G4-related disease.

Submit your answer to see the results

Overlap with other disorders
   
Lack of awareness of the condition
   
Lack of definitive biomarkers
   
Subacute nature of presentation
   
 
Watch Time: 02:33

The faculty answer questions submitted by the live audience.

 
Watch Time: 09:39

Dr Emanuel Della Torre reviews the American College of Rheumatology and European League Against Rheumatism IgG4-RD classification criteria, as well as the Japanese revised comprehensive diagnostic criteria.

Tutorial

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Poll

How confident are you with the diagnostic strategies for IgG4-RD?

 

 

Submit your answer to see the results

Not confident
   
A little confident
   
Moderately confident
   
Extremely confident
   
 
Watch Time: 04:31

The faculty answer questions submitted by the live audience.

 
Watch Time: 09:58

Dr Arezou Khosroshahi reviews current treatment strategies for IgG4-RD, as well as novel targeted agents in clinical development.

Tutorial

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Poll

Which of these factors influences your treatment choice for IgG4-RD the most?

IgG4-RD, immunoglobulin G4-related disease.

Submit your answer to see the results

Stage of presentation
   
Clinical disease phenotype
   
Predictors of relapse
   
Urgency of presentation
   
 
Watch Time: 04:16

The faculty answer questions submitted by the live audience.

 
Watch Time: 04:36

In this session, the panellists review an illustrative patient case and provide their expert perspectives on the identification and diagnosis of IgG4-RD; followed by key learnings from the symposium.

Tutorial

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Poll

If this was your patient, what additional diagnostic tests would you perform?

CT, computed tomography; Ig, immunoglobulin; PET, positron emission tomography.

Submit your answer to see the results

Biopsy to detect malignant cells; immunostain for IgG4
   
Measure response to high-dose prednisone
   
Measure serum IgG4 levels
   
PET-CT to detect pancreatic and extra-pancreatic lesions
   
 
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Overview & Learning Objectives
Overview

In this activity, leading rheumatologists come together during the American College of Rheumatology (ACR) Convergence 2023 to examine the clinical presentation of immunoglobulin G4-related disease (IgG4-RD) and typical organ involvement, review diagnostic classification criteria and current treatment options, and consider how emerging targeted therapies may impact future practice. The expert panel goes on to discuss a patient case that incorporates diagnostic and treatment strategies into clinical practice to facilitate early disease management.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of rheumatologists involved in the management of IgG4-RD.

Disclosures

Faculty

Prof. John Stone discloses: Advisory board or panel fees from Amgen, Horizon Therapeutics, IQVIA and Novartis. Consultancy fees from AbbVie, Amgen, Argenx, Bristol Myers Squibb, Connect Biopharma, Genentech, Horizon Therapeutics, IQVIA, Novartis, PPD, Prometheus Biosciences, Q32 Bio, Quell Therapeutics, Sanofi and Zenas BioPharma. Grants/research support from AbbVie, Amgen, Argenx, Bristol Myers Squibb, Connect Biopharma, Genentech, Horizon Therapeutics, IQVIA, Novartis, PPD, Prometheus Biosciences, Q32 Bio, Quell Therapeutics, Sanofi and Zenas BioPharma.

Dr Emanuel Della Torre discloses: Advisory board or panel fees from Horizon Therapeutics and Zenas BioPharma. Consultancy fees from Bristol Myers Squibb, Horizon Therapeutics, Roche, Sanofi and Zenas BioPharma (relationships terminated).

Dr Arezou Khosroshahi discloses: Advisory board or panel fees from Horizon Therapeutics. Grants/research support from Pfizer (relationship terminated).

Content reviewer

Loutfi Succari, MD, has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Directors

Katrina Lester and Kathy Day have no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu.

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Advanced Practice Providers

Physician Assistants may claim a maximum of 1.0 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 12 December 2023. Date credits expire: 12 December 2024.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

Learning Objectives

After watching this activity, participants should be better able to:

  • Describe the complex pathophysiology and clinical manifestations of IgG4-RD
  • Outline the diagnostic and classification criteria for IgG4-RD
  • Discuss current treatments for IgG4-RD as well as novel, emerging targeted treatment options
Faculty & Disclosures
Prof. John Stone

Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA

Prof. John Stone is professor of medicine and Edward A Fox Chair in Medicine at Massachusetts General Hospital (MGH), Boston, MA, USA.  read more

He received his medical degree from Harvard Medical School and has been in practice for more than 20 years. 

Prof. Stone’s long-standing interests are in clinical and translational scientific research in rheumatic diseases. His work has focused on systemic vasculitides and, more recently, on immunoglobulin G4-related disease (IgG4-RD) and glucocorticoid toxicity. 

Prof. Stone has led a number of important clinical trials in vasculitis, including the WGET, RAVE and GiACTA trials. This work led to regulatory drug approvals of rituximab for anti-neutrophil cytoplasmic antibody-associated vasculitis and tocilizumab for giant cell arteritis and Takayasu’s arteritis. The data for all three of these trials were published in The New England Journal of Medicine

Prof. Stone’s group at MGH has identified several new disease associations with IgG4-RD, including lymphoplasmacytic thoracic aortitis, eosinophilic angiocentric fibrosis and Riedel’s thyroiditis. He is the principal investigator of several trials in this area. 

Additionally, in the last couple of years, Prof. Stone’s research has focused on the measurement and prevention of glucocorticoid toxicity. This led to the development of a Glucocorticoid Toxicity Index, designed as an outcome measure for clinical trials. He is also a co-founder of a company called Steritas, which helps to reduce the world’s dependence on glucocorticoids.

Prof. John Stone discloses: Advisory board or panel fees from Amgen, Horizon Therapeutics, IQVIA and Novartis. Consultancy fees from AbbVie, Amgen, Argenx, Bristol Myers Squibb, Connect Biopharma, Genentech, Horizon Therapeutics, IQVIA, Novartis, PPD, Prometheus Biosciences, Q32 Bio, Quell Therapeutics, Sanofi and Zenas BioPharma. Grants/research support from AbbVie, Amgen, Argenx, Bristol Myers Squibb, Connect Biopharma, Genentech, Horizon Therapeutics, IQVIA, Novartis, PPD, Prometheus Biosciences, Q32 Bio, Quell Therapeutics, Sanofi and Zenas BioPharma.

Dr Emanuel Della Torre

Vita-Salute San Raffaele University and San Raffaele Hospital, Milan, Italy

Dr Emanuel Della Torre is assistant professor of rheumatology at Vita-Salute San Raffaele University and senior consultant at the Unit of Immunology, Rheumatology, Allergy, and Rare Disease of San Raffaele Hospital in Milan, Italy. read more

After receiving his medical degree and board certification in allergy and clinical immunology, and PhD in basic and applied immunology, Dr Della Torre completed his post-doc in the US at the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, in Boston, MA. Dr Della Torre returned to Italy in 2018 and established his laboratory within the Division of Genetic and Cell Biology of the San Raffaele Hospital in Milan. 

With his seminal works, Dr Della Torre has contributed to the characterization of immunoglobulin G4-related disease and is currently considered a world expert in this area.

Dr Emanuel Della Torre discloses: Advisory board or panel fees from Horizon Therapeutics and Zenas BioPharma. Consultancy fees from Bristol Myers Squibb, Horizon Therapeutics, Roche, Sanofi and Zenas BioPharma (relationships terminated).

Dr Arezou Khosroshahi

Emory University School of Medicine, Atlanta, GA, USA

Dr Arezou Khosroshahi is associate professor of medicine and director of clinical trial research at the Division of Rheumatology at the Emory University School of Medicine in Atlanta, GA, USA. read more

She received her medical degree from Tehran University Medical School in Iran and completed her residency at St. Luke’s–Roosevelt Hospital Center in New York, NY, USA. After completing her rheumatology fellowship at Massachusetts General Hospital, Harvard Medical School, she became involved in clinical research. 

Dr Khosroshahi’s main interest is in improving and advancing therapies for autoimmune diseases. She is the director of clinical trials at Emory Rheumatology. Her efforts to understand different aspects of immunoglobulin G4-related disease (IgG4-RD) over the past 10 years have led to important findings, including adding new clinical manifestations to the list of organs involved with this protean disease and its responsiveness to B-cell depletion. She co-directed the first two international symposia on IgG4-RD to bring together investigators from all around the world, and helped to establish the name of the disease, pathology statements for diagnosis and management guidelines. She is currently an active member of an international committee for the development of classification criteria and validation of the IgG4-RD Responder Index.

Dr Arezou Khosroshahi discloses: Advisory board or panel fees from Horizon Therapeutics. Grants/research support from Pfizer (relationship terminated).

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Question 1/5
When discussing with colleagues, how would you best describe the current understanding of the pathophysiology of IgG4-RD to explain why inflammation, tissue damage and fibrosis occur?

CCL18, CC-chemokine 18; CD, cluster of differentiation; CTL, cytotoxic T lymphocyte; IgG4-RD, immunoglobulin G4-related disease; IL, interleukin; PDGF, platelet-derived growth factor.
Correct

While many aspects of the pathophysiology of IgG4-RD remain unconfirmed, studies have shown that B cells play a central role in the underlying disease mechanism. In the current model, activated B cells migrate to inflamed tissues and promote T-cell expansion and differentiation into CD4+ CTLs. CD4+ CTLs release perforin and granzyme to induce apoptosis; apoptotic target cells are subsequently cleared by M2 macrophages. B cells, CD4+ CTLs and M2 macrophages produce various profibrotic cytokines that activate fibroblasts. Fibroblasts secrete ECM proteins, resulting in tissue remodelling and fibrosis.

Abbreviations

CD, cluster of differentiation; CTL, cytotoxic T lymphocyte; ECM, extracellular matrix; IgG4-RD, immunoglobulin G4-related disease. 

Reference

Perugino CA, Stone JH. Nat Rev Rheumatol. 2020;16:702–14.

Question 2/5
When reviewing patient cases, which of the following profiles would you consider to be a common presentation of IgG4-RD?

Ig, immunoglobulin; IgG4-RD, IgG4-related disease.
Correct

IgG4-RD is diagnosed at an average age of 50–70 years and the disease has a predominance in men.1 The symptoms of IgG4-RD vary according to the organs or tissues involved; however, it most commonly presents as a mass lesion or organ enlargement.2 Patients who develop exocrine pancreatic insufficiency as a result of IgG4-RD can exhibit profound or substantial weight loss.1

Abbreviation

IgG4-RD, immunoglobulin G4-related disease. 

References

  1. Katz G, Stone JH. Annu Rev Med. 2022;73;545–62.
  2. Al-Khalili O, et al. Mo Med. 2018;115:253–6.
Question 3/5
According to the 2019 ACR/EULAR classification criteria, which of the following would warrant strong suspicion of IgG4-RD?

ACR, American College of Rheumatology; EULAR, European League Against Rheumatism; IgG4-RD, immunoglobulin G4-related disease.
Correct

The 2019 ACR/EULAR IgG4-RD classification criteria includes entry, exclusion and inclusion criteria. A case must first demonstrate enlargement or a tumour-like mass in a typical organ, or pathological evidence of an inflammatory process accompanied by a lymphoplasmacytic infiltrate of uncertain aetiology. Second, none of the 24 clinical, serological, radiological or pathological exclusion criteria must be present (including multicentric Castleman’s disease and evidence of malignancy). Lastly, a score of ≥20 points across eight weighted inclusion criteria domains must be achieved.

Abbreviations

ACR, American College of Rheumatology; EULAR, European League Against Rheumatism; IgG4-RD, immunoglobulin G4-related disease.

Reference

Wallace ZS, et al. Arthritis Rheumatol. 2020;72:7–19.

Question 4/5
Your 69-year-old patient was diagnosed with IgG4-RD with kidney involvement, based on renal pathology, elevated serum IgG4 levels and enlargement of submandibular glands. Induction treatment consisted of oral prednisone at 30 mg/day for 4 weeks. Monitoring revealed prompt alleviation of submandibular gland enlargement and signs of disease activity in the kidney. What treatment strategy would you consider next?

Ig, immunoglobulin; IgG4-RD, IgG4-related disease.
Correct

The starting dose of 30–40 mg/day prednisone is recommended for patients with active IgG4-RD, maintained for 4 weeks before dose tapering over a total duration of glucocorticoid therapy of no more than 12 weeks.1 Following dose tapering, glucocorticoids are discontinued or maintained at a low dose (5–10 mg).1 However, long courses of glucocorticoids are associated with toxicity.1 Patients with IgG4-RD are particularly exposed to steroid toxicity due to their older age and potential comorbidities.2 

Abbreviation

IgG4-RD, immunoglobulin G4-related disease.

References

  1. Tanaka Y, Stone JH. Mod Rheumatol. 2023;33:229–36.
  2. Lanzillotta M, et al. Expert Rev Clin Immunol. 2021;17:471–83.
Question 5/5
Considering the pathophysiology of IgG4-RD, which of the following is a target of both inebilizumab and obexelimab, two agents currently under investigation for the treatment of IgG4-RD?

CD, cluster of differentiation; IgG4-RD, immunoglobulin G4-related disease; SLAMF7, surface antigen CD319.
Correct

Inebilizumab and obexelimab are anti-CD19 monoclonal antibodies that target CD19-positive B cells and mediate their rapid and durable depletion.1,2 Both treatments are in phase III development for IgG4-RD (NCT04540497 and NCT0566224, respectively).3 In addition to targeting CD19, obexelimab also targets the FcγRIIb on B cells.2

Abbreviations

CD, cluster of differentiation; FcγRIIb, Fcγ receptor II B; IgG4-RD, immunoglobulin G4-related disease. 

References

  1. Lanzillotta M, et al. Mod Rheumatol. 2023;33:258–65.
  2. Nakaymada S & Tanaka Y. Mod Rheumatol. 2023;33:266–70.
  3. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/; clinical trials searchable by NCT number (accessed November 2023).
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