AB0985 Methotrexate as induction of remission therapy for localized manifestations of IGG4-related disease
Authors: L Rovati, E Della-Torre, M Lanzillotta, E Bozzalla Cassione, E Bozzolo, C Canevari, M Falconi, L Dagna
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Medium to high dose glucocorticoids represents the treatment of choice for inducing remission in IgG4-related disease (IgG4-RD) patients<sup>1</sup>. However, clinicians might prefer alternative equally effective drugs in clinical settings where long-term corticosteroids treatment is contraindicated, such as diabetes or osteoporosis. We recently reported the efficacy of methotrexate in maintaining glucocorticoids induced IgG4-RD remission<sup>2</sup>. <h3>Objectives</h3> To evaluate the efficacy of methotrexate as induction of remission therapy in selected cases of mild and localized IgG4-RD complicated by clinical scenarios that might advise against corticosteroids treatment. <h3>Methods</h3> Five patients with active untreated IgG4-RD were started on oral or subcutaneous methotrexate (up to 15–20 mg/week). Efficacy of methotrexate in inducing remission was assessed at 6 months by 18F-FDG PET/CT scan and by measuring the IgG4-RD Responder Index (RI)<sup>3</sup> and circulating plasmablasts<sup>4</sup>. Partial response (PR) corresponded to an improvement of the IgG4-RD RI &gt;2 points. Complete response (CR) corresponded to an IgG4-RD RI score &lt;3. <h3>Results</h3> All patients were males with a mean age of 67 years (range 53–78). Two had pancreatic involvement; one had lymph node enlargement; one had pancreatic and lymph node involvement; one had pancreatic, aortic, submandibular gland and lymph node involvement. Patients with pancreatic involvement presented with increased serum amylases or abdominal discomfort; none had obstructive jaundice; all had overt diabetes. The mean IgG4-RD RI, serum IgG4 concentration and plasmablasts counts at baseline were 8 (6–15), 483 mg/dL (136–983) and 3336/mL (330–9330 /mL), respectively. All patients had increased 18F-FDG uptake on PET/CT scan within the affected organs. After 6 months of methotrexate, Patients 1, 2, and 3 were on CR with improved or normalized PET/CT findings, serum IgG4 and plasmablasts levels. Patient 5 achieved PR, showing improved 18F-FDG-PET/CT findings, normal plasmablasts level, but stable serum IgG4 concentration; after 10 months of methotrexate, persistence of disease activity prompted the introduction of glucocorticoids. Methotrexate was stopped in Patient 4 after 5 months because of nausea and vomiting; at 6 months he showed persistently increased plasmablasts count and 18F-FDG uptake on PET/CT, thus requiring a rescue therapy with glucocorticoids. (Table 1) <h3>Conclusions</h3> In localized forms of IgG4-RD with mild manifestations, methotrexate represents a promising alternative strategy for inducing disease remission, especially in the presence of contraindications to glucocorticoids. <h3>References</h3> Khosroshahi A, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol. 2015. Della-Torre E, et al. Methotrexate for maintenance of remission in IgG4-related disease. Rheumatology (Oxford). 2015. Carruthers MN, et al. Development of an IgG4-RD Responder Index. Int J Rheumatol. 2012. Wallace ZS, et al. Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations. Ann Rheum Dis. 2015. <h3>Disclosure of Interest</h3> None declared