Trifecta of CD-19 Receptor, IgG4 Disease and the Mitigate Trials
Abstract
1. Introduction
2. Methods
3. Discussion
3.1. Inclusion Criterion
3.2. Exclusion Criteria
3.3. Endpoints
3.4. Results of the Trial
3.5. Adverse Events
3.6. Limitations
3.7. Literature Review
3.7.1. CD19 and Characteristics
3.7.2. IgG4 Characteristics
3.7.3. MITIGATE Trials—Integration of CD-19 and IgG4—Clinical Relevance
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Outcome Measure | Definition | Details |
---|---|---|
Annualized Flare Rate (Treated and AC-Determined) | Number of flares per year | Includes both flares that required treatment and those confirmed by the Adjudication Committee (AC), regardless of treatment. |
Flare-Free, Treatment-Free Complete Remission at 52 Weeks | No disease activity or treatment required at 52 weeks | No flare (per AC), no treatment except for 8 week glucocorticoid (GC) taper and IgG4-RD Responder Index = 0 or judged inactive by investigator. |
Flare-Free, GC-Free Complete Remission at 52 Weeks | No disease activity and no GC use at 52 weeks | Same as above, but no GC treatment allowed beyond the initial 8 week taper. |
Time to First Treatment Initiation | Time from baseline to new treatment due to disease activity | Includes any medication or procedure started by the investigator for worsening/new disease, regardless of AC determination of a flare. |
Annualized Flare Rate (All AC-Determined) | Number of all AC-confirmed flares per year, whether treated or not | Standardized assessment of flare frequency, regardless of treatment. |
Cumulative Glucocorticoid (GC) Dose | Total amount of GC used during the randomized–controlled period | Calculated in mg over the 52 week trial. |
Treatment-Emergent Adverse Events (AEs) | Any new unwanted effects that started after treatment | Includes all AEs, whether mild or severe. |
Serious Adverse Events (SAEs) | AEs that are life-threatening, result in hospitalization, disability or death | Subset of AEs considered medically significant. |
Adverse Events of Special Interest (AESI) | Specific AEs identified as important to monitor | Predefined based on known risks or concerns related to the treatment. |
Organ-Specific Flare Criteria Tables—MITIGATE Trial | |
---|---|
Pancreas (autoimmune pancreatitis) | |
Criteria | |
Radiographic evidence of new/enlarging pancreatic lesion(s) | |
Worsening pancreatic function (e.g., increased lipase/amylase, diabetes onset) | |
Symptomatic recurrence (e.g., pain, jaundice) | |
Biliary tree | |
Criteria | |
New/increased biliary stricture or obstruction on imaging | |
Recurrent jaundice or cholangitis | |
Worsening liver function tests (LFTs) attributable to biliary disease | |
Salivary glands | |
Criteria | |
New or recurrent gland swelling (submandibular/parotid) | |
Pain/tenderness over glands | |
Functional impairment (dry mouth, decreased salivary flow) | |
Lacrimal glands | |
Criteria | |
Recurrent/progressive swelling or pain | |
Decreased tear production (confirmed by Schirmer test) | |
Kidneys | |
Criteria | |
New or worsening renal dysfunction (eGFR decline) | |
New or enlarging renal lesions on imaging | |
Proteinuria or hematuria due to IgG4-TIN | |
Lungs | |
Criteria | |
New or worsening pulmonary nodules, infiltrates or masses | |
Cough, dyspnea or chest pain with imaging findings | |
Decline in pulmonary function tests (PFTs) | |
Lymph Nodes | |
Criteria | |
New or enlarging lymphadenopathy on physical exam or imaging | |
Associated systemic symptoms (fever, fatigue) | |
Retroperitoneum and Aorta | |
Criteria | |
New or increased retroperitoneal fibrosis | |
Aneurysmal dilation or peri-aortic thickening | |
Obstructive uropathy or abdominal symptoms | |
Orbit | |
Criteria | |
Proptosis, diplopia or vision changes | |
Orbital mass on imaging | |
Extraocular muscle enlargement | |
Meninges (hypertrophic pachymeningitis) | |
Criteria | |
New or worsening headache | |
Focal neurological deficits | |
MRI showing thickened/dural enhancement | |
Thyroid (Riedel’s thyroiditis) | |
Criteria | |
Goiter with compressive symptoms (dysphagia, dyspnea) | |
Hypothyroidism progression | |
Imaging/lab/pathological confirmation | |
Skin | |
Criteria | |
New or worsening skin plaques, nodules or rashes | |
Histological confirmation of IgG4-related involvement | |
Prostate | |
Criteria | |
Urinary obstruction or LUTS due to prostate involvement | |
Histological confirmation if biopsied | |
Other Rare Organs (e.g., Heart, GI, Spleen) | |
Organ | Potential Flare Criteria |
Heart/pericardium | Pericardial effusion, constrictive symptoms, masses |
GI tract | Mural thickening, strictures, biopsy evidence |
Spleen | Enlargement, infarcts, lab evidence of hypersplenism |
Testes | Swelling, pain, imaging or biopsy confirmation |
Breast | Mass-like lesion with histological confirmation |
CNS (parenchyma) | Rare; neuro symptoms + imaging + biopsy |
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Jain, R.; Singh, B.; Grover, P.; Ethakota, J.; Bai, S.; Kaur, G.; Bern, M. Trifecta of CD-19 Receptor, IgG4 Disease and the Mitigate Trials. BioChem 2025, 5, 29. https://doi.org/10.3390/biochem5030029
Jain R, Singh B, Grover P, Ethakota J, Bai S, Kaur G, Bern M. Trifecta of CD-19 Receptor, IgG4 Disease and the Mitigate Trials. BioChem. 2025; 5(3):29. https://doi.org/10.3390/biochem5030029
Chicago/Turabian StyleJain, Rahul, Bipneet Singh, Palak Grover, Jahnavi Ethakota, Sakshi Bai, Gurleen Kaur, and Merritt Bern. 2025. "Trifecta of CD-19 Receptor, IgG4 Disease and the Mitigate Trials" BioChem 5, no. 3: 29. https://doi.org/10.3390/biochem5030029
APA StyleJain, R., Singh, B., Grover, P., Ethakota, J., Bai, S., Kaur, G., & Bern, M. (2025). Trifecta of CD-19 Receptor, IgG4 Disease and the Mitigate Trials. BioChem, 5(3), 29. https://doi.org/10.3390/biochem5030029