Objective
Patients with IgG4-Related Disease (IgG4RD) usually require steroid-sparing agents due to relapse with tapering glucocorticoids (GC). The aim of this study was to determine the efficacy and safety of Mizoribine (MZR) among IgG4RD, which inhibits inosine monophosphate dehydrogenase, a rate-limiting enzyme in the de novo pathway of purine synthesis.
Methods
We retrospectively reviewed records of IgG4RD patients at the Immuno-Rheumatology Center in St. Luke’s International Hospital, Tokyo, Japan. Patients were classified into the MZR combination group, and those treated with GCs 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 exacerbation.
Results
A total of 14 and 29 cases were included in the MZR combination and control groups, respectively. Multiple organ involvement (≥3 organs) was significantly more frequent in the MZR combination treatment group (10 [71.4%] vs 9 [31.0%], p= 0.021). Kaplan-Meier analysis revealed a significant reduction in exacerbation 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[0.12–1.01] (p= 0.052), and 3.51[1.29–9.51] (p= 0.014). The cumulative GC dose tended to be lower in the MZR combination group (1448[1003, 1642] vs 2179[1264, 3425]; p= 0.09).
Conclusion
MZR showed a significant steroid-sparing effect and decrease in exacerbation among IgG4RD patients with multi-organ involvement. MZR could be a treatment option for IgG4RD.
ObjectiveLong-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.MethodsData 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.ResultsIn 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.ConclusionsGlucocorticoid 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.
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.
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