Emerging therapy options for IgG4-related disease

ABSTRACT

Introduction

Awareness of IgG4-related disease (IgG4-RD) is increasing worldwide and specialists are now familiar with most of its clinical manifestations and mimickers. IgG4-RD promptly responds to glucocorticoids and repeated courses are typically used to induce and maintain remission because the disease relapses in most patients. If left untreated, it can lead to organ dysfunction, organ failure and death. Advancement in our understanding of IgG4-RD pathogenesis is leading to the identification of novel therapeutic targets and emerging treatments are now setting the stage for personalized therapies for the future.

Areas covered

This review focuses on emerging treatment options for IgG4-RD based on our advancing understanding of disease pathophysiology. Research was performed in the English literature on Pubmed and clinicaltrials.gov databases.

Expert opinion

Glucocorticoids remain the first-line induction treatment for the multi-organ manifestations of IgG4-RD. Alternative immunosuppressive agents for maintaining remission are warranted in order to avoid long-term steroid toxicity, and to offer a more mechanistic and personalized therapeutic strategy. Targeting B and T-lymphocyte activation represents the most promising approach, but randomized controlled trials are eagerly awaited to confirm positive preliminary experiences reported in case series and small cohort studies.

KEYWORDS:

• Abatacept
• biologic
• corticosteroids
• fibrosis
• glucocorticoids
• igg4
• igg4-related disease
• rituximab
• treatment
• therapy

Article Highlights

• Glucocorticoids still represent the cornerstone for inducing disease remission in patients with active IgG4-RD but chronic treatment is often required to prevent disease flare, thus exposing patients to high risk of steroid-related toxicity in the long term.

• Traditional immunosuppressive agents such as azathioprine, mycophenolate mofetil, methotrexate, and cyclophosphamide have been used in combination with corticosteroids to maintain disease remission, but little evidence exists for their additional efficacy as steroid-sparing agents.

• A portfolio of target therapeutic options for IgG4-RD is emerging in parallel with the discovery of novel pathogenic insights.

• B-cell depletion with rituximab is currently the most widely used mechanistic approach to both induce and maintain remission of relapsing forms of IgG4-RD.

• Based on available pathogenic evidence, targeting cytotoxic T-cells and T-follicular helper cells represents the most promising future therapeutic strategy in alternative to B-cell depletion.

• The emergence of a variety of targeted treatments together with a growing awareness of the clinical phenotypes of IgG4-RD offer the opportunity to consider personalized medical approaches and tailored therapeutic strategies.

Declaration of interest

AFC received consulting fees from Atheneum Partners, Boehringer Ingelheim, Actelion and Bayer. AFC received a grant from the Spanish Society for Internal Medicine. FMV received consulting fees from Pfizer, Alnylam and Viela-Medpace. FMV received an ASPIRE grant from Pfizer. EDT received consulting fees from Viela-Medpace and Xencor. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.