mycophenolic-acid and Immunoglobulin-G4-Related-Disease

To assess the safety and efficacy of glucocorticoids (GCs), immunosuppressive agents (IM) and rituximab (RTX), alone or in combination, for the treatment of IgG4-RD.. Relevant articles published were searched in the databases with relevant key words. Network meta-analysis was conducted, with various outcomes including relapse rate, remission rate and adverse events. Data were calculated with odds ratio (ORs) and 95% CI. P-score was used to rank the treatments.. A total of 15 studies involving 1169 patients were included. Network meta-analysis indicated that RTX maintenance therapy had the lowest relapse rate of all treatments (OR = 0.10, 95% CI [0.01, 1.63]), whereas GCs + IM was associated with a lower relapse rate compared with GCs alone (OR = 0.39, 95% CI [0.20, 0.80]). Further, patients treated with GCs + IM had a higher remission rate than those given GCs (OR= 3.36, 95% CI [1.44, 7.83]), IM (OR= 55.31, 95% CI [13.73, 222.73]) monotherapies or RTX induction therapy only (OR= 7.38, 95% CI [1.56, 34.94]). The rate of adverse events was comparable among the different treatment groups.. Treatment of IgG4-RD patients with GCs and IM was associated with higher remission rates and lower relapse rates, as well as comparable safety profiles compared with GC, IM and RTX induction therapy. RTX maintenance therapy had a larger reduction in the relapse rate compared with GC and IM. The current evidence should be carefully scrutinized as the included studies were observational in design. Larger randomized controlled trials are needed to confirm.

Topics: Antirheumatic Agents; Azathioprine; Cyclophosphamide; Cyclosporine; Drug Therapy, Combination; Glucocorticoids; Humans; Immunoglobulin G4-Related Disease; Immunosuppressive Agents; Maintenance Chemotherapy; Mercaptopurine; Methotrexate; Mycophenolic Acid; Network Meta-Analysis; Odds Ratio; Recurrence; Remission Induction; Rituximab; Tacrolimus

This randomized, controlled clinical trial aims to compare the efficacy and safety of glucocorticoid combined with MMF and glucocorticoid monotherapy for patients with IgG4-related disease.. Sixty-nine patients newly diagnosed with IgG4-related disease were randomly divided into two groups (35 patients in Group I and 34 patients in Group II). Patients in Group I received glucocorticoid monotherapy (0.6-0.8 mg/(kg·day) and tapered gradually); patients in Group II received glucocorticoid combined with MMF therapy (1-1.5 g/day). All the patients were followed up at 1, 3, 6 and 12 months. The primary endpoint was response rate in 12 months and the secondary endpoints were relapse, remission rate and adverse reactions.. Group I and Group II shared almost the same efficacy at the 1 month treatment, but during the follow-up, the complete response rate in Group II was much higher than that in Group I at different time points, and the cumulative relapse rate during 1 year of therapy was much higher in Group I than that in Group II (40.00 vs 20.59%). The remission rate was lower in Group I (51.42 vs 76.47%). Relapses were more likely to happen in lung, lacrimal gland, salivary gland, paranasal sinus and kidney. MMF could reduce relapse, especially organs recurrence. No serious adverse reactions occurred in the two groups.. Combination treatment with glucocorticoid and MMF was more effective than the monotherapy, and the relapse of IgG4-related disease might be associated with the elevated levels of serum IgG4 and the low glucocorticoid maintenance dose.. ClinicalTrials.gov, www.clinicaltrials.gov, NCT02458196.

Topics: Adult; Aged; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunoglobulin G4-Related Disease; Immunosuppressive Agents; Induction Chemotherapy; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Treatment Outcome

Combination therapy of glucocorticoids (GCs) plus leflunomide (LEF) and GCs plus mycophenolate mofetil (MMF) was reported to have good efficacy and safety in the management of IgG4-RD. However, studies comparing the efficacy and safety of these two combination therapies were unavailable. Herein, this study aimed to compare the efficacy and safety of GCs plus LEF and GCs plus MMF in treating IgG4-RD.. This study included 130 newly diagnosed IgG4-RD patients who received the therapy of GCs plus LEF (group I) and GCs plus MMF (group II). Clinical data at baseline and after treatment, treatment response, relapse rate, and adverse effects were recorded and analyzed.. Patients in both groups responded well to the treatment in the 1st-month follow-up, and 100% of patients achieved treatment response. However, at the 6th and 12th-month follow-up, the total response rate of group II was higher than that in group I (75.6 vs. 53.7%, p = 0.038 and 85.4% vs. 61.0%, p = 0.013, respectively). In addition, the duration of disease remission in group II was longer than that in group I (9 (6-9) vs. 6 (6-6) months, p = 0.014). Moreover, more patients in group I had adverse effects compared with group II (36.6 vs. 7.3%, p < 0.01); and the most common adverse events of LEF were rash (12.2%) and elevation of liver enzymes (9.8%).. The combination therapy of GCs plus low-dose MMF had better efficacy and safety in the management of IgG4-RD compared with the therapy of GCs plus LEF.

Topics: Drug Therapy, Combination; Glucocorticoids; Humans; Immunoglobulin G4-Related Disease; Immunosuppressive Agents; Leflunomide; Mycophenolic Acid; Remission Induction; Retrospective Studies; Treatment Outcome

Topics: Amyloidosis; Female; Glucocorticoids; Humans; Immunoglobulin G4-Related Disease; Immunologic Factors; Mycophenolic Acid; Prednisone; Rituximab; Young Adult

To evaluate the therapeutic efficacy and safety of iguratimod on patients with relapsed or refractory IgG4-related disease (IgG4-RD).. We conducted a retrospective single-center study in 17 IgG4-RD patients admitted to Peking University People's Hospital. Patients were given iguratimod, 25 mg, twice daily and clinical data were collected at 0, 12, and 24 weeks. The baseline treatments include prednisone, cyclophosphamide, leflunomide, mycophenolate mofetil, and methotrexate. Clinical manifestation, IgG4-RD responder index (IgG-RD RI), serological indexes, gland ultrasound findings, and adverse drug effect were recorded. IgG4-RD RI scores < 3 and declining ≥ 2 were recognized as complete response (CR); IgG4-RD RI scores declining ≥ 2 but remaining ≥ 3 were recognized as partial response (PR). If a patient's IgG4-RD RI score was 3 at the beginning, PR was considered as a 1-point decrease after the therapy.. Serum IgG4 decreased significantly from 708 (321-902) mg/dl at baseline to 446 (138-396) mg/dl at 24 weeks (P = 0.0016). IgG4-RD RI decreased significantly from 9.79 ± 3.07 at baseline to 3.57 ± 1.09 at 24 weeks (P < 0.0001). Overall, 2 (14.3%) patients achieved CR, 11 (78.6%) patients achieved PR, and 1 (7.14%) patient had no response to treatment at week 24. Serum IgG level and salivary glands major diameter also decreased significantly at week 12 and 24 after treatment.. Iguratimod can be a therapeutic strategy to achieve remission in relapsed or refractory IgG4-RD patients inadequately responding to corticosteroid treatment with or without other immunosuppressant treatment. Key messages • Iguratimod was effective for relapsed or refractory IgG4-RD patients. • Iguratimod can improve the clinical symptoms of patients, reduce the serum IgG and IgG4 levels, and can also reduce the volume of involved glands.

Topics: Adult; Aged; Chromones; Cyclophosphamide; Female; Glucocorticoids; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Immunosuppressive Agents; Lacrimal Apparatus; Leflunomide; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Prednisone; Recurrence; Retrospective Studies; Salivary Glands; Sulfonamides; Treatment Outcome; Young Adult

Topics: Anti-Inflammatory Agents; Biopsy; Diagnosis, Differential; Humans; Immunoglobulin G4-Related Disease; Male; Middle Aged; Mycophenolic Acid; Phlebitis; Prednisone; Radiographic Image Enhancement; Radiography, Abdominal; Spermatic Cord; Splenic Vein; Tomography, X-Ray Computed; Treatment Outcome

Patients with IgG4-related disease (IgG4-RD) typically respond well to initial glucocorticoid therapy, but always relapse with tapered or maintenance dosage of steroid. We aimed to identify the risk factors for relapse of IgG4-RD and explore the impact of active intervention on the serologically unstable condition.. We performed a retrospective study of 277 IgG4-RD patients at Peking University People's Hospital from February 2012 through February 2019. They were all followed for >4 months. The primary outcome was patient relapse. Data on recurrence of IgG4-RD symptoms, laboratory and image findings were recorded, along with information on treatment in the serologically unstable condition.. The cumulative relapse rate was 12.86%, 27.84% and 36.1% at 12, 24 and 36 months, respectively. Younger age at onset, younger age at diagnosis, longer time from diagnosis to treatment and history of allergy were associated with relapse. Identified independent risk factors were longer time from diagnosis to treatment and history of allergy. When serum IgG4 level was 20%, 50% or 100% higher than that of the remission period, similar percentages of patients finally relapsed, regardless of whether they were in the immunosuppression intensified or non-intensified group. Median duration from serum IgG4 level instability to relapse in the intensified and non-intensified group was not statistically different.. The risk factors of relapse were longer time from diagnosis to treatment and history of allergy. Intervention in the serologically unstable condition was not helpful for reducing relapse rate.

Topics: Adult; Age Factors; Azathioprine; Biomarkers; Cyclophosphamide; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Prognosis; Recurrence; Retrospective Studies; Risk Factors; Treatment Outcome

Immunoglobulin (Ig)G4-related disease (IgG4-RD) is an unusual complication of systemic lupus erythematosus (SLE). We report a case in which belimumab proved efficacious for not only SLE, but also IgG4-RD. A 58-year-old Japanese woman had suffered from photodermatosis and erythema on the limbs for 20 years. She presented in slight fever and fatigue since 2016. Laboratory data showed hypergammaglobulinemia, proteinuria and positive results for anti-nuclear antibody and anti-double-stranded DNA antibody. Furthermore, elevated levels of serum IgG4 were detected. Contrast-enhanced computed tomography disclosed multiple areas of poor enhancement in the kidneys. The patient was diagnosed with lupus nephritis and IgG4-RD from renal biopsy. Treatment was started with prednisolone at 40 mg/day and mycophenolate mofetil. Proteinuria and serological findings improved initially, but tapering the dose of glucocorticoid proved difficult. After treatment was started with belimumab, clinical symptoms and proteinuria resolved completely. The dose of glucocorticoid was successfully tapered and serum concentration of IgG4 fell further. This appears to represent the first report of a case in which both SLE and IgG4-RD were effectively treated using belimumab.

Topics: Antibodies, Antinuclear; Antibodies, Monoclonal, Humanized; Female; Fever; Humans; Immunoglobulin G4-Related Disease; Immunosuppressive Agents; Kidney; Lupus Nephritis; Middle Aged; Mycophenolic Acid; Proteinuria; Tomography, X-Ray Computed

IgG4-related disease (IgG4-RD) is an autoimmune disease triggering an inflammatory cascade that leads to fibrosis. Outcome measures are limited and treatment options remain underexplored.. To assess the variation of the IgG4 responder index (IgG4-RI) in a cohort of IgG4-RD patients and to explore their treatments and outcomes.. We studied the clinical phenotype, severity of the disease and response to treatment in an ambispective multicenter cohort study including 14 different hospitals in Spain. All patients met the 2012 international consensus on pathology criteria for diagnosis.. Sixty-eight patients were included, with a mean age of 53.4 years and predominance of male sex. The most commonly involved tissues were: retroperitoneum (33%), orbital pseudotumor (28%) and maxillary and paranasal sinuses (24%). IgG4-RI values were higher in patients with multiorgan disease and before treatment. After being treated, IgG4-RI values were lower, in accordance with the high rates of treatment response. Most patients received: glucocorticoids (GC), surgery, azathioprine (AZA), mofetil mycophenolate or rituximab. GC alone, GC plus surgery and GC plus AZA were given in the most of the IgG4-RD disease activity episodes. All treatments had high response rates but relapses and flares were common.. IgG4-RI is a promising outcome measure in IgG4-RD, but still in development. Treatment algorithms are ill defined. GC and rituximab are the drugs with more evidence available. Disease modifying anti-rheumatic drugs may have a role in IgG4-RD and warrant more prospective studies.

Topics: Adult; Aged; Azathioprine; Biomarkers; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Glucocorticoids; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Immunologic Factors; Male; Middle Aged; Mycophenolic Acid; Remission Induction; Retrospective Studies; Rituximab; Treatment Outcome

The aim of this study was to assess the outcomes of remission induction in patients with IgG4-related disease (IgG4-RD) in our cohort, and to investigate the characteristics, prognosis, and risk factors in the patients failed of remission induction.. We prospectively enrolled 215 newly diagnosed patients with IgG4-RD, who were initially treated with glucocorticoid (GC) alone or in combination with immunosuppressive agents (IM), and had at least 6 months of follow up. The therapeutic goals of remission induction were defined as fulfilling each of the following after the 6-month remission induction stage: (1) ≥ 50% decline in the IgG4-RD responder index (RI); (2) GC tapered to maintenance dose; and (3) no relapse during GC tapering. The patients not achieving the therapeutic goals were considered to have failed of remission induction.. There were 26 patients in our cohort who failed of remission induction, including 16 (20.8%) on GC monotherapy, and 10 (7.2%) on combination therapy comprising GC and IM. The lacrimal gland and lung were most common sites of remission induction failure. Among the patients who relapsed during remission induction stage, 52.9% had secondary relapse during follow-up. Eosinophilia, higher baseline RI, more than five organs involved and dacryoadenitis were risk factors for remission induction failure with GC monotherapy, and the incidence of remission induction failure was 71.4% in the patients with more than three risk factors. After 6-month treatment, the patients who failed of remission induction had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and IgG4.. In our cohort, 20.8% of patients failed of remission induction with GC monotherapy, while 7.2% of patients failed of remission induction with combination therapy comprising GC and IM.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azathioprine; Child; Cohort Studies; Cyclophosphamide; Cyclosporine; Female; Glucocorticoids; Glycosides; Humans; Immunoglobulin G4-Related Disease; Immunosuppressive Agents; Leflunomide; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Prednisone; Prospective Studies; Remission Induction; Treatment Outcome; Young Adult