‘Watchful waiting’ may raise risk of relapse for those with mild IgG4-RD
Real-world study found over 40% using strategy experienced disease flare
Written by |
Closely monitoring disease activity without starting medication immediately — an approach called watchful waiting — may raise the risk of relapse for people with mild IgG4-related disease (IgG4-RD), according to a real-world study from China.
In people with IgG4-RD, watchful waiting is sometimes used as a strategy for patients with mild disease (meaning low disease activity) when concerns arise that the side effects of standard treatment options may outweigh the potential benefits of early therapy.
However, the researchers found, using patient data, that more than 40% of individuals whose mild IgG4-RD was managed with watchful waiting experienced a disease relapse. That compared with fewer than 1 in 10 of those who started treatment early, the data showed.
Within the watchful waiting group, relapses were especially frequent among patients who underwent surgical removal of affected tissues without subsequent medical therapy — which, the team noted, occurred in about two-thirds of cases.
Overall, the findings led the researchers to conclude that a watchful waiting strategy “may not be the optimal immediate choice for patients with mild symptoms, low disease activity, and limited organ involvement, even after the surgical [removal of tissues].”
Still, larger studies are needed to confirm the results and better define which patients might safely delay treatment, the team noted.
The study, “Reassessing the role of watchful waiting strategy for IgG4-related disease: a real-world study,” was published in the journal Arthritis Research & Therapy.
IgG4-RD is a chronic, immune-mediated condition in which immune cells infiltrate healthy tissues, causing inflammation that can lead to tumor-like masses and scarring (fibrosis) in multiple organs.
Initial treatment for IgG4-RD typically involves glucocorticoids
The symptoms of IgG4-RD vary depending on the organs affected, but often follow a relapsing-remitting course, with periods of worsening disease activity, known as relapses or flares, alternating with times when symptoms lessen or stabilize.
First-line or initial IgG4-RD treatment usually involves glucocorticoids, part of a class of steroid hormones. These drugs are typically started at higher doses to rapidly control inflammation before gradual tapering. Long-term low-dose maintenance glucocorticoid therapy may be required to control symptoms and avoid complications in certain patients at higher risk of relapse.
However, long-term use of glucocorticoids can have serious side effects. As such, glucocorticoid-sparing immunosuppressive agents may be added to help reduce glucocorticoid dosage or discontinue them altogether. However, immunosuppressive treatments may in turn increase the risk of severe infections.
Overall, concerns that medications’ side effects may outweigh the benefits of starting treatment early can prompt doctors to consider a wait-and-see, or watchful waiting, approach for IgG4-RD patients without symptoms or mild disease. The idea is to delay treatment until disease activity increases, so as to prevent unwanted side effects from therapy.
However, “its efficacy compared to medical intervention has not been thoroughly evaluated,” the researchers wrote.
Medical records used to compare treatment vs. watchful waiting
To address this gap, a team led by researchers from Huazhong University of Science and Technology retrospectively analyzed data from 710 people with IgG4-RD treated at Tongji Hospital in Wuhan between October 2018 and October 2022.
According to international treatment guidelines, 49 patients met criteria for a watchful waiting approach. Among these patients were individuals with disease limited to either the head or neck and no symptoms, or who had involvement of other minor organs and no symptoms. Some had undergone surgical removal of affected tissue and remained symptom-free afterward.
The median age of these patients was 54, and slightly more than half (61%) were women. All had been living with the disease for an average of months. In 63%, the condition affeccted a single organ or tissue, most commonly the salivary glands below the jaw (33% of cases). Most participants (71%) had a head- and neck-limited clinical profile.
Disease activity at enrollment, assessed with the validated IgG4-RD Responder Index, was generally mild.
A total of 25 participants (51%) opted for the watch-and-see approach, while 24 (49%) accepted treatment with the glucocorticoid prednisone and glucocorticoid-sparing agents. Patients were followed for 48 months, or about four years.
Although patients in the watchful waiting group had significantly lower disease activity at the start, they were significantly more likely to experience relapses over time. During follow-up, 42% of people managed with watchful waiting had a relapse, compared with about 8% of those who started medication.
The researchers noted that 16 of the 25 patients on the watchful waiting strategy underwent biopsy — where a small tissue sample is taken and analyzed under a microscope — and surgical removal of affected tissue. Biopsy is usually done to exclude cancer and confirm an IgG4-RD diagnosis, while surgical removal of localized lesions can help to ease symptoms.
‘Rigorous monitoring’ essential when wait-and-see approach is used
No relapses were seen among watch-and-wait patients who did not undergo surgery. However, 68% of those who had affected tissue removed and did not receive medication afterward experienced relapses, the data showed.
Five patients experienced recurrence in the same organ originally affected, while the other five showed relapses in new organs. Two of these cases were marked by particularly severe flares that progressed from one to seven involved organs.
Our finding indicates that timely medication intervention might be more appropriate than [an] initial ‘watchful waiting’ strategy for IgG4-RD patients with low disease activity.
The researchers noted that removing the affected tissues — a procedure known as local surgical resection — may appear to resolve inflammation at the site, but it is unlikely to address the underlying immune processes driving IgG4-RD. This may explain why the disease often recurs after tissue removal, sometimes with more severe flare-ups.
“Our finding indicates that timely medication intervention might be more appropriate than [an] initial ‘watchful waiting’ strategy for IgG4-RD patients with low disease activity,” the researchers concluded.
The team also emphasized that, while watchful waiting may be appropriate for carefully selected patients, it should be paired with “rigorous monitoring” to detect early signs of disease progression. This would allow timely treatment and may improve long-term outcomes, the team noted.
