IgG4ward! Question of the Week: “How is the effectiveness of B cell depletion determined after the treatment is administered?”
We are pleased to start our new IgG4ward! Question of the Week (QoW) series! The first QoW and its answer are below. We invite you to join the Online Community and share any follow-up questions or comments you might have about the QoW there.
“How is the effectiveness of B cell depletion determined after the treatment is administered?”
An excellent question (!), and one that is likely to be even more relevant in the coming months as we approach the potential approval of a B cell depletion therapy.
In terms of gauging clinical responses, we think in terms of several parameters:
Symptoms
Signs
Serological measures
Radiology studies
Indications of improvement may be seen in some or all of these parameters.
Symptoms
How does the patient feel after a B cell depletion treatment is administered? Patients generally feel better immediately, at least in part (a large part, probably) because steroids – 100 milligrams of methylprednisolone – are also given along with B cell depletion to help reduce the severity of any infusion reaction that occurs.
Signs
“Signs” in this context refers to physical examination findings. Within 3-4 weeks and sometimes even sooner, one may appreciate substantial improvement in the size of the major salivary glands that are often involved in IgG4-RD. Examples: the submandibular glands and parotid glands. One may also see dramatic improvement in the eye swelling that is associated with orbital involvement.
Serological measures
Many patients with IgG4-RD have markers of the disease that are elevated in the blood and correlate well with disease activity: rising with active disease and declining as the disease comes under control. We refer to these markers in the blood as “biomarkers”. The most reliable one, not surprisingly, is IgG4. We will discuss IgG4 in more detail in the upcoming Conversation series (watch this Online Community space!). In general, however, IgG4 begins a steady decline following B cell depletion and is a useful biomarker of ongoing disease response to treatment.
Other biomarkers in the blood that are useful in some patients are IgE and IgG1. Both IgE and IgG1 tend to decline following B cell depletion. Finally, serum complement levels – specifically those known as C3 and C4 – tend to become lower when the disease is ACTIVE, and to rise toward normal levels after B cell depletion is administered.
Radiology studies
Radiology studies such as X-rays, CT scans, and PET scans are not performed routinely in all patients following B cell depletion but they may be useful in some types of organ involvement, to document improvement in organs that are otherwise difficult to evaluate.
In summary, the great majority of patients with IgG4-RD respond well to B cell depletion treatment, and it is typically easy to document this improvement by reviewing these four parameters.
If you have a follow up question or comment, please share your feedback in the IgG4ward! Online Community.
