IgG4 disease- the WInS withdrawal study results Save

IgG4-related disease (IgG-RD) describes a group of fibroinflammatory diseases whose features may include autoimmune pancreatitis, swelling of or within an organ system (an inflammatory pseudotumor), salivary gland disease (which can lead to enlargement of the salivary glands), swollen lymph nodes (lymphadenopathy), skin manifestations, and symptoms consistent with allergies or asthma.

Withdrawal of Immunosuppressant and Low-dose Steroids in IgG4-RD Patients with Stable Disease (WInS IgG4-RD) trial has shed light on effective strategies for the maintenance treatment of IgG4-RD (abstract#L16). While remission induction treatment with glucocorticoids (GC) has proven effective, the high relapse tendency is an ongoing challenge for clinicians.

This multicenter, open-label, randomized controlled trial focused on stable IgG4-RD patients who had been receiving GC and immunosuppressive agents (IM) for maintenance treatment with clinically quiescent disease for at least 12 months. The trial had 146 patients, utilized a 1:1:1 randomization, and explored three groups: Group 1 withdrew GC and IM, Group 2 withdrew GC but maintained IM, and Group 3 continued with both GC and IM. The primary endpoint of the study was the relapse rate of the disease within 18 months, with secondary endpoints encompassing changes in responder index (RI), physician’s global assessment (PGA), serum IgG4 and IgG levels, and adverse events.

Interestingly, the trial revealed that maintaining IMs, with or without low-dose GC, proved superior in preventing relapse compared to withdrawing both GC and IM in long-time stable IgG4-RD patients. Within the 18-month follow-up period, Group 1 experienced a significantly higher relapse rate (52.1%) compared to Group 2 (14.2%) and Group 3 (12.2%), highlighting the efficacy of IMs as a maintenance strategy. Furthermore, changes in RI and PGA were significantly more pronounced in the group that withdrew GC and IM compared to those who maintained either or both treatments.

This pivotal finding not only addresses the challenges associated with IgG4-RD relapse but also provides valuable insights into optimizing maintenance treatments for this complex fibroinflammatory disease. This is no different from withdrawal studies at ACR this year in other rheumatic diseases. We as clinicians need to counsel patients adequately about the risks of withdrawal.