The goal of treatment is the induction and maintenance of
remission so as to prevent progression of fibrosis and organ destruction in affected organ(s). An international panel of experts have developed recommendations for the management of IgG4-RD. They concluded that in all cases of symptomatic, active IgG4-RD that treatment is required. Some cases with
asymptomatic IgG4-RD also require treatment, as some organs tend to not cause symptoms until the late stages of disease. Urgent treatment is advised with certain organ manifestations, such as
aortitis,
retroperitoneal fibrosis, proximal biliary
strictures,
tubulointerstitial nephritis,
pachymeningitis,
pancreatic enlargement and
pericarditis.
Induction of remission In untreated patients with active disease, the recommended
first-line agent for induction of
remission is
glucocorticoids unless
contraindications exist. Glucocorticoids characteristically result in a rapid and often dramatic improvement in clinical features and often a resolution of
radiographic features. However, where advanced fibrotic lesions have resulted in irreversible damage, the response to glucocorticoids and other current treatment options may be poor or even absent. Although not validated yet in clinical trials, the common induction regime is
prednisolone 30–40 mg per day for 2–4 weeks, then gradually tapered over 3 to 6 months. Recurrences during or after tapering of glucocorticoids are frequent, however.
Steroid-sparing immunosuppressive agents might be considered, depending on local availability of these drugs, for use in combination with glucocorticoids from the start of treatment in order to reduce the
side-effects of prolonged glucocorticoid usage. Steroid-sparing agents that have been used include
rituximab,
azathioprine,
methotrexate, and
cyclophosphamide, although trials are needed to ascertain the effectiveness of each drug in IgG4-RD.
Maintenance Following a successful induction of remission, maintenance therapy might be given in some cases, for example when there is a high risk of relapse or in patients with organ-threatening manifestations. Common maintenance therapy is
prednisolone 2.5–5 mg per day, or use of a steroid-sparing agent instead.
Relapse Relapses are common, and a previous history of relapse appears to be a strong predictor of future relapse. When relapse occurs while off therapy and there has been a prolonged disease remission following initial glucocorticoid induction, then the relapse can usually be managed successfully with a re-induction strategy using glucocorticoids. Introducing a
steroid-sparing agent might also need to be considered for relapses; however, none has been tested in prospective, controlled studies, and evidence for their efficacy beyond that offered by concomitant glucocorticoid therapy is scarce. In one retrospective cohort study, baseline concentrations of serum IgG4, IgE and blood eosinophils were found to be independently predictive of relapse risk following treatment with
rituximab with or without glucocorticoids; the higher the baseline values, the greater the relapse risk and the shorter the time to relapse.
Other interventions When organ involvement causes local mechanical problems, further organ-specific interventions may be necessary. For example, when a tumefactive lesion causes obstruction of the
bile duct, it may be necessary to insert a biliary
stent to allow the
bile to drain freely. Similarly, ureteral or vascular stents, surgical resection or radiotherapy may be considered for various different presenting problems.
Trials Research is also underway to evaluate the effect and safety of plasmablast-directed therapy with a
monoclonal antibody (XmAb5871, obexelimab) which inhibits
B-cell function without depleting these immune cells. ==Epidemiology==