Changes in alcohol intake and serum urate changes: longitudinal analyses of annual medical examination database.

INTRODUCTION: Despite the established cross-sectional association between alcohol intake and serum urate (SU), its longitudinal association remains unknown. This study aimed to determine whether changes in alcohol intake have a clinically relevant association with SU change. METHOD: We conducted retrospective analyses using systematically collected annual medical examination data from October 2012 to October 2022 in a Japanese preventive medicine centre. The exposure was changes in alcohol intake between two consecutive visits. The association of SU changes with alcohol intake changes was estimated by mixed-effect linear regression with adjustment for relevant covariates. RESULTS: We analysed 63 486 participants (median age, 47.0 years; 55% women; 58.6% regular alcohol drinkers with a median of 1.4 drinks/day) with 370 572 visits. The median SU level was 5.3 mg/dL, and 506 (0.8%) participants had diagnoses of gout or hyperuricemia without medication use during the study period. Decreasing one daily alcohol intake had a clinically small association with SU changes (-0.019 (95% CI: -0.021 to -0.017) mg/dL). Beer had the largest association with SU (-0.036 (95% CI: -0.039 to -0.032) mg/dL for one beer decrease). Complete discontinuation of any alcohol from a mean of 0.8 drinks/day was associated with -0.056 mg/dL (95% CI: -0.068 to -0.043) decrease in SU; the association became larger in hyperuricemic participants (-0.110 mg/dL (95% CI: -0.154 to -0.066) for alcohol discontinuation from a mean of 1.0 drinks/day). CONCLUSIONS: This study revealed changes in alcohol intake had small associations with SU change at the general Japanese population level. Complete discontinuation of alcohol in hyperuricemic participants had only modest improvement in SU.

Disease-modifying effect and long-term safety of belimumab in patients with systemic lupus erythematosus: A single-center retrospective study.

BACKGROUND: Disease modification in systemic lupus erythematosus (SLE) is important for minimizing disease activity while limiting treatment-associated toxicities. Belimumab can be used as a remission-induction/maintenance systemic lupus erythematosus therapy; however, its disease-modifying effects are unclear. We aimed to determine these effects in patients with systemic lupus erythematosus. METHODS: This single-center retrospective cohort study included 92 patients with systemic lupus erythematosus treated with belimumab. We analyzed the changes in flare free rate/lupus low disease activity state (LLDAS) attainment rate/glucocorticoid dosage/Systemic Lupus International Collaborating Clinics and American College of Rheumatology damage index (SDI) score/drug retention rate after treatment initiation. RESULTS: Fifty-two weeks after initiating belimumab, the flare rate decreased from 82.6% to 14.1% (p < .01). Until week 52 and 1000 days after initiating belimumab treatment, > 70% and ∼90% of the patients attained lupus low disease activity state, respectively. Belimumab treatment significantly reduced glucocorticoid demand (initiation day, 8.88 (6.00-15.00) mg/d; week 52, 5.00 (2.00-7.00) mg/d; final day of the study period, 3.00 (0.46-6.06) mg/d, initiation day vs. week 52: p < .01, initiation day vs. final day: p < .01); at the end of the study period, 68.5% of patients required ≤5 mg/d prednisolone, and 22.8% discontinued glucocorticoids. Most patients were SDI progression-free (week 52, ∼95%; day 1000, ∼90%), and belimumab showed a high drug retention rate (week 52, 90%; day 1000 > 80%). CONCLUSION: Most patients experienced lupus low disease activity state, reduced flare rate and glucocorticoid demand, and a stable SDI trend after belimumab treatment initiation. Given its efficacy and retention rate, belimumab treatment may serve as a fundamental strategy in disease modification.

Risk factors associated with relapse after methotrexate dose reduction in patients with rheumatoid arthritis receiving golimumab and methotrexate combination therapy.

AIM: To identify risk factors for relapse after methotrexate (MTX) dose reduction in rheumatoid arthritis (RA) patients receiving golimumab (GLM)/MTX combination therapy. METHOD: Data on RA patients ≥20 years old receiving GLM (50 mg) + MTX for ≥6 months were retrospectively collected. MTX dose reduction was defined as a reduction of ≥12 mg from the total dose within 12 weeks of the maximum dose (≥1 mg/wk average). Relapse was defined as Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) score ≥3.2 or sustained (≥ twice) increase of ≥0.6 from baseline. RESULTS: A total of 304 eligible patients were included. Among the MTX-reduction group (n = 125), 16.8% of patients relapsed. Age, duration from diagnosis to the initiation of GLM, baseline MTX dose, and DAS28-CRP were comparable between relapse and no-relapse groups. The adjusted odds ratio (aOR) of relapse after MTX reduction was 4.37 (95% CI 1.16-16.38, P = 0.03) for prior use of non-steroidal anti-inflammatory drugs (NSAIDs), and the aORs for cardiovascular disease (CVD), gastrointestinal disease and liver disease were 2.36, 2.28, and 3.03, respectively. Compared to the non-reduction group, the MTX-reduction group had a higher proportion of patients with CVD (17.6% vs 7.3%, P = 0.02) and a lower proportion of prior use of biologic disease-modifying antirheumatic drugs (11.2% vs. 24.0%, P = 0.0076). CONCLUSION: Attention should be given to RA patients with history of CVD, gastrointestinal disease, liver disease, or prior NSAIDs-use when considering MTX dose reduction to ensure benefits outweigh the risks of relapse.

Differences in the Association Between Alcoholic Beverage Type and Serum Urate Levels Using Standardized Ethanol Content.

Importance: Differences have been observed in the association of serum urate levels with consumption of different types of alcoholic beverages. However, previous studies have not standardized the unit of intake for ethanol content, and only limited types of alcoholic beverages have been evaluated. Objective: To examine differences in the association of serum urate levels with various types of alcoholic beverages when their intakes are standardized for ethanol content. Design, Setting, and Participants: This retrospective cross-sectional study was conducted using data from participants aged 20 years or older who completed a medical checkup at St Luke's International University in Japan between October 1, 2012, and October 31, 2021. Participant demographics, blood test results, and lifestyle questionnaire data were used as covariates. Analysis was performed in December 2021. Exposures: Consumption of alcoholic beverages, including beer, sake (rice wine), shochu (Japanese spirit), wine, and whiskey. Main Outcomes and Measures: Serum urate levels were measured during the medical checkup. The beverage unit was standardized to 1 standard drink, which contained 20 g of ethanol. Multivariable linear regression including interaction terms of alcohol consumption and dominant alcoholic beverage was performed. Results: This study included 78 153 participants. Their mean (SD) age was 47.6 (12.8) years; 36 463 (46.7%) were men and 41 690 were women (53.3%). A total of 45 755 participants (58.5%) were regular alcohol drinkers. Consistent associations of serum urate levels with alcohol consumption were observed in the beer-dominant group, with ß coefficients (for 1 standard drink per day) of 0.14 mg/dL (95% CI, 0.11-0.17 mg/dL; P < .001) for men and 0.23 mg/dL (95% CI, 0.20-0.26 mg/dL; P < .001) for women. A moderate increase in serum urate levels was observed in the wine-dominant group compared with a modest and nonsignificant increase in the sake-dominant group, with ß coefficients (for 1 standard drink per day) for the latter group of 0.05 mg/dL (95% CI, -0.01 to 0.10; P = .10) for men and 0.04 mg/dL (95% CI, -0.05 to 0.14 mg/dL; P = .38) for women. Restricted cubic splines showed different patterns in associations of serum urate levels with ethanol intake by dominant alcoholic beverages. Conclusions and Relevance: The results of this study suggest that the extent of the association of serum urate levels with alcohol intake was different for alcoholic beverages even after ethanol content was standardized. Higher beer consumption among men and women was consistently associated with higher serum urate levels, whereas sake was not associated with changes in serum urate levels. Therefore, alcoholic beverage type, in addition to ethanol content, should be considered as a factor contributing to hyperuricemia.

Antimicrobial therapy for nontuberculous mycobacterial pulmonary disease improved hearing loss and normalized myeloperoxidase-anti-neutrophil cytoplasmic antibody level: A case report.

Several case reports have indicated that nontuberculous mycobacterial pulmonary disease is associated with anti-neutrophil cytoplasmic antibody-associated vasculitides. However, the effect of the treatment for nontuberculous mycobacterial pulmonary disease on anti-neutrophil cytoplasmic antibody-associated vasculitides remains unclear. An asymptomatic 80-year-old woman presented with nodular bronchiectasis. After 1 year, she developed a productive cough. Mycobacterial culture of the respiratory specimen revealed Mycobacterium avium. She was diagnosed with nontuberculous mycobacterial pulmonary disease based on the criteria proposed by the American Thoracic Society. Concurrently, she had hearing loss, tinnitus, and weight loss. A blood test showed an elevated level of myeloperoxidase-anti-neutrophil cytoplasmic antibody (107 IU/mL, normal level: <3.5 IU/mL). Bilateral otitis media with anti-neutrophil cytoplasmic antibody-associated vasculitis was diagnosed based on the diagnostic criteria proposed by the Japan Otological Society. After starting antimicrobial agents for the nontuberculous mycobacterial pulmonary disease, her pulmonary symptoms and hearing loss improved, and the level of myeloperoxidase-anti-neutrophil cytoplasmic antibody normalized. No immunosuppressive treatment was administered. The present case suggests that nontuberculous mycobacterial pulmonary disease can cause otitis media with anti-neutrophil cytoplasmic antibody-associated vasculitides, and antimicrobial treatment for the nontuberculous mycobacterial pulmonary disease may resolve otitis media with anti-neutrophil cytoplasmic antibody-associated vasculitides.

Endothelial Damage-dominant Nephritis Related to IgA Vasculitis after 11 Years' Use of Infliximab for Rheumatoid Arthritis.

A 43-year-old Japanese woman with rheumatoid arthritis treated by infliximab and methotrexate for 11 years was admitted for proteinuria and purpura. A kidney biopsy revealed endothelial damage-dominant nephritis with IgA deposition. Infliximab and methotrexate were discontinued, and tocilizumab was started; however, proteinuria persisted. Therefore, tocilizumab was discontinued, and oral prednisolone and methylprednisolone pulse therapy were administered. After 6 months, urinary protein was less than 0.1 g/day, and purpura subsided. To our knowledge, this is the first case of endothelial damage-dominant nephritis related to IgA vasculitis involving the skin and kidney after long-term use of infliximab and methotrexate.

A case report of two systemic lupus erythematosus pregnancies with early placental exposure to belimumab: Case report with review.

Since its approval for the management of systemic lupus erythematosus (SLE), belimumab has been widely used. However, its pregnancy safety profile has been underinvestigated. We present the pregnancy outcomes of two cases of early placental exposure to belimumab and summarise the pregnancy outcomes in previous reports regarding placental exposure to belimumab. Case 1 describes a 27-year-old woman with an 18-year history of SLE and lupus nephritis class III. We introduced belimumab 19 months prior to conception to control her proteinuria and discontinued its use at 5 weeks and 5 days of gestation. Her lupus activity was stable throughout pregnancy, and at 37 weeks and 1 day of gestation, she delivered a healthy girl with no anomaly. At delivery, the girl was small for gestational age, but at the 1-year follow-up, there was no delay in her growth or any serious infection. Case 2 describes a 32-year-old woman with a 15-year history of SLE. We introduced belimumab 9 months prior to conception and discontinued its use at 7 weeks and 1 day of gestation. Although her lupus was well controlled without belimumab, a missed abortion occurred, which was possibly due to foetal factors. Although there is accumulating data on the safety of belimumab use during pregnancy, it seems necessary to cautiously use this medication in pregnant women, until further analyses are conducted.

Advantages of an alternate-day glucocorticoid treatment strategy for the treatment of IgG4-related disease: A preliminary retrospective cohort study.

Alternate-day glucocorticoid (GC) therapy is a treatment option that can reduce GC-associated adverse events. We investigated the safety and efficacy of alternate-day GC therapy in patients with immunoglobulin G4-related disease (IgG4-RD). Medical records of patients with IgG4-RD who were followed for at least one year at St. Luke's International Hospital, Tokyo, Japan, from 2004 to 2020 were reviewed. Patients who fulfilled comprehensive IgG4-RD diagnostic criteria were divided into alternate-day or daily GC treatment groups based on their treatment protocol. The effect of alternate-day GC therapy on glucocorticoid toxicity index (GTI) score was evaluated using multilinear analysis with adjustments for cumulative GC doses until each assessment point and propensity scores (PS) for alternate-day GC therapy. Kaplan-Meier curves and Cox proportional hazard models were used to assess the efficacy of alternate-day GC therapy for disease control. Among the 67 patients with IgG4-RD, patients with alternate-day (n = 13) and daily (n = 31) GC treatments were analyzed after excluding 23 ineligible patients. The median (interquartile range) age was 64 (60-70) years, 29 (65.9%) were male patients, 26 (59.1%) patients had positive biopsy results, and the median follow-up period was 1643 days. Significantly more patients with alternate-day GC treatment used concomitant immunosuppressants (11 [84.6%] vs 11 [35.5%]; P = .007). The alternate-day strategy significantly lowered the GTI score after adjusting for cumulative GC dose until the assessment and PS (adjusted coefficient: -29.5 [-54.3, -4.8], P = .021 at 12 months; -20.0 [-39.8, -0.1], P = .049 at 24 months). Serious infections were numerically less frequent in the alternate-day group (incidence ratio [95% confidence interval [CI]: 0.45 [0.05, 3.63], P = .45). Most patients (92.3%) in the alternate-day GC treatment group and all patients in the daily GC treatment group showed treatment responses in the remission induction therapy. The PS-adjusted hazard ratio of alternate-day GC treatment for disease flares was not significant (1.55 [0.53, 4.51]; P = .43). The alternate-day treatment strategy significantly reduced GC-related adverse events regardless of the cumulative GC dose. Alternate-day GC treatment is a feasible option for patients with IgG4-RD, without a significant increase in disease flares particularly when combined with immunosuppressants.

A Spotlight on Drug-Induced Vasculitis.

PURPOSE OF REVIEW: Drug-induced vasculitis (DIV) is a rare form of vasculitis related to the use of various drugs. DIV primarily affects small to medium size vessels, but it can potentially involve vessels of any size. Differentiating between primary systemic vasculitis and DIV can be challenging; however, it is crucial, so that the offending agent can be discontinued promptly. RECENT FINDINGS: The clinical phenotype of DIV is protean and depends on the size of the affected vessels. It ranges from arthralgias, to an isolated cutaneous rash, to severe single or multi-organ involvement. While withdrawal of the offending drug is the most important step in management, a significant number of patients require immunosuppressive therapy for varying periods of time. DIV can affect any vascular bed size, leading to protean vasculitic syndromes. Increased awareness among general practitioners, specialty, and subspecialty physicians is crucial for early recognition, and withdrawal of drug for better outcomes.

Effect and safety profile of belimumab and tacrolimus combination therapy in thirty-three patients with systemic lupus erythematosus.

INTRODUCTION/OBJECTIVES: Belimumab combined with mycophenolate mofetil has been proven to be effective for treating systemic lupus erythematosus (SLE) in several randomized controlled trials. Calcineurin inhibitors are also useful in controlling the activity of SLE. However, the safety and effectiveness of belimumab-calcineurin inhibitor combination therapy have not been addressed. Therefore, the current single-center retrospective study aimed to analyze the safety/efficacy profile of belimumab-tacrolimus (B-T) combination therapy in patients with SLE. METHOD: Patients with SLE administered tacrolimus and belimumab during treatment were included in the study. Samples were analyzed for the drug retention rate, SLE flare rate, infection incidence rate, and glucocorticoid-sparing effect of the B-T combination therapy. RESULTS: Thirty-three patients with SLE were treated with B-T combination therapy at our institution. Four patients discontinued treatment due to insufficient response or adverse events. The drug retention rate was over 90% at week 52 and approximately 80% at day 1000. Only one patient developed serious infection. The lupus low disease activity state (LLDAS) achievement ratio was 9.1% on the day of initiation and improved to 64.0% at 52 weeks after initiation. SLE flares were observed in three patients (9.1%) in the first 52 weeks after initiation, and in five patients (15.2%) throughout the study period. A glucocorticoid-reducing effect was also observed in patients treated with B-T combination therapy. CONCLUSIONS: In most patients with SLE, B-T combination therapy is well tolerated with a good efficacy profile and glucocorticoid-reducing effect. Thus, B-T combination therapy represents a feasible option for patients with refractory lupus. Key Points • The safety and effectiveness of belimumab-calcineurin inhibitor combination therapy have not been addressed. • The drug retention rate of belimumab-tacrolimus combination therapy was over 90% at week 52 and around 80% on day 1000 • Almost none of the patients suffered from severe infection after the initiation of belimumab-tacrolimus combination therapy. • Belimumab-tacrolimus combination therapy is efficacious in suppressing lupus activity and achieving LLDAS.

Recurrence rate of venous thromboembolic events in granulomatosis with polyangiitis.

Objective: The incidence of first-time venous thromboembolic events (VTEs) is high in granulomatosis with polyangiitis (GPA). The incidence of recurrent VTEs is unknown. We aimed to describe the recurrence rate of second VTEs in patients with GPA. Methods: Retrospective chart review was performed in patients with GPA and at least one VTE at a single centre from 2002 to 2016. Inclusion criteria were 1990 ACR criteria or 2012 Revised International Chapel Hill nomenclature for GPA, at least two follow-up visits, at least one VTE during the study period, and VTE occurrence after or within 3 months before GPA diagnosis. Second VTE event-free survival rates were estimated. Results: Out of 147 patients initially screened for GPA and with at least one VTE, 84 met inclusion criteria. Median age at first VTE was 57 years. Incidence rate for second VTE was 8.4 events per 100 patient-years (95% CI: 5.7, 12.3). Eighty-three point three per cent of first VTEs and 57.7% of second VTEs occurred when disease was active (P < 0.001). Renal involvement and constitutional symptoms at the time of first VTE were associated with VTE recurrence. Conclusion: GPA has a high rate of VTE recurrence compared with the reported data in the general population with unprovoked VTE. Our results suggest that VTE in GPA is a recurrent co-morbidity, not always during active vasculitis, and more so in those with renal involvement and constitutional symptoms at the time of first VTE.

Glucocorticoid discontinuation in patients with SLE with prior severe organ involvement: a single-center retrospective analysis.

OBJECTIVE: Long-term glucocorticoid use in SLE may have significant side effects; however, glucocorticoid discontinuation is occasionally associated with disease flare-ups. Therefore, we evaluated the risk factors for disease flares and the flare rate on glucocorticoid tapering in patients with prior severe organ involvement. METHODS: Data of patients with SLE with glucocorticoid tapering at our institution were retrospectively analysed. We divided the patients by the presence of prior severe organ involvement and compared flare rates after glucocorticoid discontinuation. Furthermore, we determined risk factors for flares after glucocorticoid discontinuation. RESULTS: In total, 309 patients with SLE were screened, 73 of whom met the inclusion criteria; 49 were classified as SLE with prior severe organ involvement. No significant differences were noted in the 52-week flare rate after glucocorticoid discontinuation between patients with and without prior severe organ involvement (16.7% vs 18.2%, p=1.0). Hypocomplementaemia, elevated anti-dsDNA antibody titres more than twice the upper limit of the laboratory reference range, positive anti-Smith/anti-ribonucleoprotein antibody, and use of any immunosuppressant on the day of glucocorticoid discontinuation were negatively associated with flare-free remission. CONCLUSIONS: Glucocorticoid discontinuation after gradual tapering can often be achieved in patients with SLE, even with prior severe organ involvement, especially when the disease is clinically and serologically stable.

Immunoglobulin G4-related coronary periarteritis: a systematic literature review with a case series.

We aimed to assess the clinical and radiological characteristics of immunoglobulin G4-related coronary periarteritis through a systematic literature review and from our case series. In the systematic literature review, we assessed English language manuscripts on immunoglobulin G4-related coronary periarteritis cases. Additionally, we identified patients with immunoglobulin G4-related coronary periarteritis at St. Luke's International Hospital in Tokyo, Japan, from 2014 to 2020. We summarized patients' demographics, immunoglobulin-G and -G4 titers, site and morphological features of the coronary lesion, and other organ involvements. We identified 38 cases from the literature and four patients from our institute. Coronary lesions were detected using coronary computed tomography in 40 (95.2%) patients. Mass-like or diffuse wall-thickening lesion was the most frequently observed type in 33 (78.6%) patients. No trends at the site of the coronary arteries were identified. Overall, 32 (76.1%) patients had multiple-organ involvement, of which the most common lesion was peri-aortitis in 21 (50.0%) patients. Ten (23.8%) patients with an isolated coronary lesion had significantly lower immunoglobulin-G4 titers than those with other organ involvements (immunoglobulin-G4: 261 [161.0, 564.0] vs. 1355.0 [320.8, 2480.0] mg/dL, p = 0.033). The wall-thickening lesions responded well to immunosuppressive treatments. Mass-like or diffuse wall-thickening on coronary computed tomography is a characteristic radiographic finding of immunoglobulin G4-related coronary periarteritis, which can occur in any branch. Immunoglobulin G4-related coronary periarteritis showed similar characteristics to other organ lesions, including its relatively low serum immunoglobulin-G4 level in patients with a single-organ disease and its high responsiveness to glucocorticoids.

Clinical significance of monitoring hypothyroidism in patients with autoimmune rheumatic disease: a retrospective cohort study.

We evaluated whether thyroid function test (TFT) screening is warranted for patients with autoimmune rheumatic diseases (ARD) by comparing the incidence of hypothyroidism requiring treatment (HRT) in ARD patients and healthy controls (HCs). Medical records of 2307 ARD patients and 78,251 HCs for whom thyroid-stimulating hormone (TSH) levels were measured between 2004 and 2018 were retrospectively reviewed. Cumulative incidence of HRT in ARD patients and HCs was compared. HRT development was evaluated with age- and sex-adjusted Kaplan-Meier curve. Risk factors were identified with Cox proportional hazard models. HRT was significantly more common in ARD patients than in HCs (6.3% vs. 1.9%, P < 0.001). After adjusting for age, sex, and baseline TSH level, hazard ratios for HRT were significantly higher in overall ARD patients (hazard ratio [95% confidence interval] 3.99 [3.27-4.87]; P < 0.001), particularly with rheumatoid arthritis and antinuclear antibody-associated diseases in female, and antinuclear antibody-associated diseases, spondyloarthritis, and vasculitis in male patients. Baseline high TSH level, thyroid-related autoantibody positivity, high IgG, and renal impairment were significant risk factors for hypothyroidism development in ARD patients; 20% of high-risk patients developed HRT during follow-up. HRT was significantly more frequent in ARD patients. Careful TFT screening and follow-up could help detecting clinically important hypothyroidism.

Performance of a pre-administration infection screening questionnaire in patients with rheumatoid arthritis administered biological disease-modifying antirheumatic drugs.

AIM: Pre-administration screening of active infections is imperative for the safe use of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). However, a standardized screening method is lacking. We therefore implemented a novel systematic screening method with a simple predetermined questionnaire on infections and assessed its effectiveness. METHODS: We retrospectively reviewed medical records of individuals for whom intravenous bDMARDs were administered for RA from January 2016 to April 2019. We evaluated the performance of the new screening method based on physicians' assessments. In addition, a survey was administered to nurses, regarding their assessment of the usefulness of this new screening. The incidence of infections was also assessed. RESULTS: A total of 1636 cases underwent this new screening. The new screening method showed high sensitivity (0.97) and specificity (0.89) with a negative predictive value of 99.9%, as determined based on the physician's decision. Administration of bDMARDs was postponed in 37 (2.5%) patients, and there was only one case in which the screening failed to note an active infection. The nurses' survey demonstrated high agreement (87.5%) about the usefulness of this screening on the grounds of clarity, simplicity, ease, and time-saving effects. There was no significant increase in infections after implementation of this method. CONCLUSIONS: Systematic screening with a predetermined simple questionnaire is effective as an infection screening method, with a high negative predictive value. This approach contributes to high satisfaction of nurses and a time-efficient practice by focusing on screen-positive cases without increasing infections.

Effectiveness and safety of mizoribine for the treatment of IgG4-related disease: a retrospective cohort study.

OBJECTIVE: Patients with IgG4-related disease (IgG4RD) usually require steroid-sparing agents due to relapse with tapering glucocorticoids (GC). We aimed to determine the efficacy and safety of mizoribine (MZR) among IgG4RD patients. METHODS: We retrospectively reviewed records of IgG4RD patients at Immuno-Rheumatology Center in St. Luke's International Hospital, Tokyo, Japan. Patients treated with MZR were classified into the MZR group, and those treated with GC alone or with other immunosuppressants were included in the control group. Disease exacerbation, GC dose, IgG-IgG4 titre and adverse events were evaluated using univariate analyses, including the Kaplan-Meier method. The Cox proportional hazard model was used to evaluate risk factors for disease exacerbation. RESULTS: A total of 14 and 29 cases were included in the MZR and control group. Multiple organ involvement (three or more organs) was significantly more frequent in the MZR group [10 (71.4%) vs 9 (31.0%), P= 0.021]. Kaplan-Meier analysis revealed a significant reduction inexacerbation in patients with multiple organ involvement (P< 0.001) but not in total (P= 0.42). The adjusted hazard ratios of MZR use and multiple organ involvement for exacerbation were 0.34 (95%CI 0.12-1.01; P = 0.052) and 3.51 (95%CI 1.29-9.51; P= 0.014). The cumulative GC dose (mg per year, interquartile range) tended to be lower in the MZR group [1448 (1003-1642) vs 2179 (1264-3425); P= 0.09]. CONCLUSION: MZR decreased disease exacerbation among IgG4RD patients with multi-organ involvement and showed a steroid-sparing effect. MZR could be a treatment option for IgG4RD.