Initial Glucocorticoid Research Articles

Relapse predictors and serologically unstable condition of IgG4-related disease: a large Chinese cohort.

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.

Long-term remission, relapses and maintenance therapy in adult primary central nervous system vasculitis: A single-center 35-year experience.

To evaluate long-term treatment and outcomes of patients with primary central nervous system vasculitis (PCNSV). In this cohort of 191 consecutive patients with PCNSV seen at Mayo Clinic, Rochester, MN, over 35years with long-term follow-up we analyzed response to and duration of therapy, frequency of relapses, long-term remission, efficacy of maintenance therapy and initial intravenous glucocorticoid (GC) pulses, survival and degree of disability. We also compared the efficacy of initial IV and oral cyclophosphamide (CYC). A favorable initial response was observed in 83% of patients treated with prednisone (PDN) alone, 81% of those treated with PDN and CYC and 95% of those initially treated with PDN and an immunosuppressant other than CYC. One or more relapses were observed in 30% of patients, 35% had discontinued therapy by last follow-up, and 21.5% maintained remission for at least 12months after discontinuing therapy. Maintenance therapy was prescribed in 19% of all patients and 34% of patients initially treated with CYC and PDN. High disability scores (Rankin 4-6) and deaths were less frequently observed in patients receiving maintenance therapy and more frequently in patients with Aβ-related angiitis. Large vessel involvement and cerebral infarction at diagnosis were associated with a poor treatment response. Aspirin use was positively associated with long-term remission and having gadolinium-enhanced cerebral lesions or meninges was negatively associated. A high disability score at last follow-up and higher mortality rate were associated with increasing age, cerebral infarction and cognitive dysfunction at diagnosis. Lymphocytic vasculitis on biopsy was associated with a more benign course with reduced disability and mortality. Patients initially treated with mycophenolate mofetil had better outcomes compared to those treated with CYC and PDN. No therapeutic advantages were observed in the patients initially treated with intravenous GC pulses. Intravenous and oral CYC were equally effective in inducing the remission. The majority of patients with PCNSV responded to treatment. We found patient subsets with different outcomes. Mycophenolate mofetil may be an effective alternative to CYC.

Additive effect of leflunomide and glucocorticoids compared with glucocorticoids monotherapy in preventing relapse of IgG4-related disease: A randomized clinical trial

ObjectivesTo evaluate the efficacy and safety of leflunomide (LEF) and glucocorticoids (GCs) combination therapy compared with GCs monotherapy in preventing relapse of IgG4-related disease (IgG4-RD). MethodsA 12-month, randomized, open-label, controlled trial was conducted at a large academic medical center (ClinicalTrials.gov: NCT02703194). Enrolled patients with active IgG4-RD were randomly allocated to the GCs + LEF (20 mg/day) combination therapy or GCs monotherapy group. All patients received GCs with a predefined taper regimen starting from a dosage of 0.5–0.8 mg/kg/d. The primary outcome was the time to relapse. The secondary outcomes included complete response, remission, GCs dosage, and serum IgG4 level. ResultsSixty-six patients with active IgG4-RD were enrolled (33 patients in each group). The demographic and disease characteristics showed no statistically significant differences between groups. Additionally, the initial GCs dosages were similar (50.00 vs. 50.00 mg/day, P = 0.295). Disease relapses occurred in 6 (18.2%) and 14 (42.4%) patients in the combination therapy group and GCs monotherapy group, respectively (P = 0.032). The combination therapy was significantly superior to GCs monotherapy regarding the primary outcome, the time to relapse (HR, 0.35; 95% confidence interval [CI], 0.13–0.90; P = 0.023), as well as the secondary outcome, the time to complete response (HR, 1.75; 95% CI, 1.01–3.02; P = 0.034). A longer duration of remission was observed in the combination therapy group (7.00 vs. 3.00 months, P = 0.002) and less cumulative dosage of GCs was used (5103.13 vs. 5637.50 mg, P = 0.031). Additionally, a higher proportion of patients in the combination therapy group (54.5%) were able to reach a daily GCs dose of ≤5 mg/day compared with the GCs monotherapy group (18.2%) (P = 0.006). The incidences of adverse events were similar in the 2 groups (P = 0.325). ConclusionLEF in combination with GCs therapy is well-tolerated and significantly superior to GCs monotherapy in preventing the relapse of IgG4-RD. LEF can be used as a steroid-sparing agent in the management of IgG4-RD.

Serum Biomarkers Related to Glucocorticoid-Induced Osteonecrosis of the Femoral Head: A Prospective Nested Case-Control Study.

Early diagnosis and prevention of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) continues to be a challenging problem for clinicians and researchers. However, the role of circulating biomarkers for GC-induced ONFH, which may reveal individual susceptibility and facilitate earlier diagnosis, remains to be determined. The aim of this study was to identify potential biomarkers that may predict early GC-induced ONFH. A total of 123 patients scheduled for initial systemic GC therapy were enrolled in this prospective nested case-control study. The serum concentrations of 13 potential biomarkers were measured in seven patients with GC-induced ONFH, diagnosed instantly after short-term use of GCs and in 20 controls who did not develop osteonecrosis despite similar GC therapy. Biomarkers were measured both before and after taking GCs to identify any differences in marker levels and the changes during GC therapy between two groups. Type I collagen cross-linked C-telopeptide (β-CTX; p = 0.000) was significantly lower, high-density lipoprotein cholesterol (p = 0.092) and apolipoprotein (apo)-B/apo-A1 (p = 0.085) tended to be lower and higher, respectively, before GC treatment in osteonecrosis group. After GC therapy, β-CTX (p = 0.014) was significantly lower and amino terminal telopeptide of procollagen type I (PINP; p = 0.068) tended to be lower in the osteonecrosis group. As secondary outcomes, we observed remarkable changes in nine potential biomarkers following short-term GC therapy in both groups. In conclusion, we found that β-CTX, could potentially be used to predict GC-induced ONFH before GC therapy. Lower β-CTX and PINP are promising biomarkers for the early diagnosis of GC-induced ONFH. These findings need to be confirmed in large-scale prospective studies. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2348-2357, 2019.

Genetic Predispositions of Glucocorticoid Resistance and Therapeutic Outcomes in Polymyalgia Rheumatica and Giant Cell Arteritis.

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related chronic inflammatory diseases. Glucocorticoids (GCs) are first-choice drugs for PMR and GCA, although some patients show poor responsiveness to the initial GC regimen or experience flares after GC tapering. To date, no valid biomarkers have been found to predict which patients are at most risk for developing GC resistance. In this review, we summarize PMR- and GCA-related gene polymorphisms and we associate these gene variants with GC resistance and therapeutic outcomes. A limited number of GC resistance associated-polymorphisms have been published so far, mostly related to HLA-DRB1*04 allele. Other genes such ICAM-1, TLR4 and 9, VEGF, and INFG may play a role, although discrepancies are often found among different populations. We conclude that more studies are required to identify reliable biomarkers of GC resistance. Such biomarkers could help distinguish non-responders from responders to GC treatment, with concomitant consequences for therapeutic strategy.

Glucocorticoids dosing in obese subjects: A systematic review

Glucocorticoids (GCs) are amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. In obese subjects, drug dosing adjusted by body weight is problematic, all the more so as patients are at higher risk of GC metabolic side effects. We propose here to describe the determinants of drug pharmacokinetics (PK) in obese subjects and GC pharmacology, and to identify the existing PK studies that may help discussing the best size descriptor for GC dosing in obese subjects. A clinician and a pharmacist screened PubMed using the MeSH Terms: "glucocorticoids" OR "steroidal agents" AND "pharmacokinetics" AND "obesity" OR "overweight". The search was limited to the publications written in English language and to those performed in humans. A systematic search using the MeSH terms was performed until August 31st, 2017. Only three such PK studies have been published so far that compare dexamethasone, prednisolone and methylprednisolone in obese and normal weight subjects. The studies concur that GC partially distribute in the excess of body weight and that adjustment by total body weight (TBW) or by body weight (BW) excess would increase the initial plasma GC concentration after a loading dose and would thus be inappropriate. Contradictory results are observed regarding GC exposure or clearance according to the GC studied. Behind this overwhelming lack of conclusive evidence for adjusting GC by body weight, further PK studies are clearly needed for guiding their dosing. Furthermore, studies demonstrated an increased sensibility to GC, even when GC exposure was reduced, suggesting that adjustment by body weight may not only be unnecessary but also dangerous.

Permanent Discontinuation of Glucocorticoids in Polymyalgia Rheumatica Is Uncommon but May Be Enhanced by Amino Bisphosphonates.

The duration of treatment with glucocorticoids (GC) in polymyalgia rheumatica (PMR) is often longterm. Amino bisphosphonates (N-BP) are used in PMR for the prevention of GC-induced osteoporosis, but they coulsd also have immunomodulatory properties. Whether they can be effective as an adjuvant treatment in PMR is unknown. We aimed to establish whether the use of N-BP in our PMR cohort may be associated with GC discontinuation. We conducted a retrospective review of all patients diagnosed with PMR recorded in our electronic medical notes. Cox regression analyses were used to examine the association between the use of N-BP and discontinuation of GC. Data were retrieved for 385 patients (mean age 71 ± 10 yrs, 64% females, mean initial prednisone dose 19 ± 9 mg/day). The median followup time was 38 months (range 9-57); more than 60% of patients were exposed to N-BP. GC were discontinued in 47% of patients after a median time of 20 months (range 14-27), but subsequently restarted in 39%. Overall, 276/385 patients (72%) were actively treated at their last available evaluation (mean prednisone dose 4.9 ± 5.5 mg/day), while 123/205 (60%) were still receiving GC after 24 months of followup. The use of N-BP was associated with the discontinuation of GC (adjusted HR 0.66, 95% CI 0.50-0.88), independent of age, initial GC dose, and osteoporosis. Unlike current guidelines, longterm treatment with GC is often necessary. These preliminary data suggest that N-BP may be involved in the management of PMR.

Factors in glucocorticoid regimens associated with treatment response and relapses of IgG4-related disease: a multicentre study

Glucocorticoids (GC) are effective for treating IgG4-related disease (IgG4-RD); however, relapse is often observed. We conducted a retrospective multicentre study to investigate risk factors in GC regimens associated with relapses of IgG4-RD. Data on 166 patients with definitive IgG4-RD diagnosis were collected from 12 institutions. Comprehensive surveillance of clinical backgrounds and GC regimens as well as multivariate analysis of factors associated with treatment responses and relapses was performed. To determine the initial maximal GC dose, the patients were stratified into three groups depending on the initial prednisolone (PSL) dosage: <0.39, 0.4–0.69 and >0.7 mg/kg/day. The multivariate analysis extracted the disease duration and reduction speed of initial GC dose. Patients treated with initial GC <0.39 or >0.7 mg/kg/day of PSL showed higher relapse rates than those treated with 0.4–0.69 mg/kg/day. The relapse rates were significantly higher in patients with fast reduction of the initial dose (>0.4 mg/day) than in patients with slow reduction (<0.4 mg/day). To avoid relapse, 0.4–0.69 mg/kg/day of initial PSL with slow reduction speed (<0.4 mg/day) is needed in the early treatment of IgG4-RD.

76-Year-Old Man With New Bilateral Shoulder Pain

76-Year-Old Man With New Bilateral Shoulder Pain

Clinical characteristics and prognosis of pediatric patients with B cell acute lymphoblastic leukemia relapse.

The aim of the present study was to investigate the clinical characteristics and prognosis of pediatric patients with B cell acute lymphoblastic leukemia (B-ALL) relapse. A total of 390 pediatric patients diagnosed as B-ALL and receiving regular chemotherapy in Jining First People's Hospital from August 2010 to May 2016 were selected. The clinical characteristics, therapeutic response and prognosis were compared between the two groups. There were significant differences in the comparisons of age, leukocyte count in the initial diagnosis and glucocorticoid sensitive test between B-cell ALL (B-ALL) relapse group and non-relapse group; the minimal residual disease (MRD) levels of pediatric patients in the two groups at 33 days and 12 weeks were significantly different. The 3-year event-free survival (EFS) rates of pediatric patients with early, medium and late B-ALL relapse were 12.5±7.8%, 33.1±9.8% and 63.6±6.1%, respectively, and the prognosis of late relapse was significantly better than that of early relapse (P<0.001). The 3-year EFS rates of pediatric patients with bone marrow relapse in standard risk group, intermediate risk group and high risk group were 29.1±6.9, 31.3±6.5 and 28.3±6.3%, respectively; there were no statistically significant differences (P=0.387, P>0.05). Pediatric patients with B-ALL relapse are characterized by higher onset age (≥10 years old), high leukocyte count and hormone insensitivity. Dynamic monitoring of MRD level in B-ALL pediatric patients can predict the relapse.

Transitional changes in the incidence of osteonecrosis in systemic lupus erythematosus patients: focus on immunosuppressant agents and glucocorticoids

The purpose of this study was to investigate transitional changes in the incidence of glucocorticoid-associated osteonecrosis in SLE patients, with a focus on immunosuppressive agent and glucocorticoid consumption. We retrospectively registered 185 SLE patients with 740 joints, who were newly diagnosed and hospitalized for initial high-dose glucocorticoid therapy from 1986 to 2015. Immunosuppressive agent, glucocorticoid dose, age, sex, organ lesion at hospitalization, complement (C3, C4, CH50) and anti-DNA antibody before initial glucocorticoid therapy, the frequency of use of anticoagulant and antilipidemic drugs, and incidence of osteonecrosis were documented. Based on trends in immunosuppressive agent use, 116 patients treated from 1986 to 1999, before calcineurin inhibitors were introduced, comprised the past group, and 69 patients treated from 2000 to 2015 comprised the recent group. Patient characteristics (age, sex and organ lesion at hospitalization, complement, anti-DNA antibody, the frequency of use of anticoagulant and antilipidemic drugs) were similar between groups. Glucocorticoid doses were significantly lower in the recent group than in the past group (highest daily glucocorticoid dose, 45.7 vs 59.0 mg/day, respectively; dose per weight, 0.88 vs 1.16 mg/day/kg, respectively; and cumulative dose at 3 months, 3118 vs 3985 mg). The incidence of osteonecrosis was significantly lower in the recent group than in the past group (26.4 vs 41.0%, respectively), particularly in the knee (25.4 vs 46.6%, respectively). The incidence of glucocorticoid-associated osteonecrosis in SLE patients decreased in association with a decrease in glucocorticoid administration after introduction of immunosuppressant agents.

Korean Guideline for the Prevention and Treatment of Glucocorticoid-induced Osteoporosis

Background To develop guidelines and recommendations to prevent and treat glucocorticoid (GC)-induced osteoporosis (GIOP) in Korea. Methods The Korean Society for Bone and Mineral Research and the Korean College of Rheumatology have developed this guideline based on Guidance for the Development of Clinical Practice Guidelines ver. 1.0 established by the National Evidence-Based Healthcare Collaborating Agency. This guideline was developed by adapting previously published guidelines, and a systematic review and quality assessment were performed. Results This guideline applies to adults aged ≥19 years who are using or plan to use GCs. It does not include children and adolescents. An initial assessment of fracture risk should be performed within 6 months of initial GC use. Fracture risk should be estimated using the fracture-risk assessment tool (FRAX) after adjustments for GC dose, history of osteoporotic fractures, and bone mineral density (BMD) results. All patients administered with prednisolone or an equivalent medication at a dose ≥2.5 mg/day for ≥3 months are recommended to use adequate calcium and vitamin D during treatment. Patients showing a moderate-to-high fracture risk should be treated with additional medication for osteoporosis. All patients continuing GC therapy should undergo annual BMD testing, vertebral X-ray, and fracture risk assessment using FRAX. When treatment failure is suspected, switching to another drug should be considered. Conclusions This guideline is intended to guide clinicians in the prevention and treatment of GIOP.

Korean Guideline for the Prevention and Treatment of Glucocorticoid-induced Osteoporosis.

BackgroundTo develop guidelines and recommendations to prevent and treat glucocorticoid (GC)-induced osteoporosis (GIOP) in Korea.MethodsThe Korean Society for Bone and Mineral Research and the Korean College of Rheumatology have developed this guideline based on Guidance for the Development of Clinical Practice Guidelines ver. 1.0 established by the National Evidence-Based Healthcare Collaborating Agency. This guideline was developed by adapting previously published guidelines, and a systematic review and quality assessment were performed.ResultsThis guideline applies to adults aged ≥19 years who are using or plan to use GCs. It does not include children and adolescents. An initial assessment of fracture risk should be performed within 6 months of initial GC use. Fracture risk should be estimated using the fracture-risk assessment tool (FRAX) after adjustments for GC dose, history of osteoporotic fractures, and bone mineral density (BMD) results. All patients administered with prednisolone or an equivalent medication at a dose ≥2.5 mg/day for ≥3 months are recommended to use adequate calcium and vitamin D during treatment. Patients showing a moderate-to-high fracture risk should be treated with additional medication for osteoporosis. All patients continuing GC therapy should undergo annual BMD testing, vertebral X-ray, and fracture risk assessment using FRAX. When treatment failure is suspected, switching to another drug should be considered.ConclusionsThis guideline is intended to guide clinicians in the prevention and treatment of GIOP.

Glucocorticoid therapy causes contradictory changes of serum Wnt signaling-related molecules in systemic autoimmune diseases.

The objective of this study was to investigate the clinical significance of the Wnt/β-catenin signaling pathway in glucocorticoid-induced osteoporosis. A total of 91 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60mg daily) were prospectively enrolled. We measured serum levels of N-terminal peptide of type I procollagen (P1NP), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), N-telopeptide cross-linked type I collagen (NTX), sclerostin, Dickkopf-1 (Dkk-1), and Wnt3a before starting glucocorticoid therapy and every week for 4weeks after its initiation. The effects of dexamethasone on expression of mRNA and protein of sclerostin and Dkk-1 by cultured normal human osteoblasts (NHOst) were evaluated by RT-PCR and ELISA, respectively. Serum levels of sclerostin and Dkk-1 increased significantly by 1week of glucocorticoid therapy and then decreased from the second week onward. Serum Wnt3a tended to decrease and serum P1NP showed a significant decrease. However, TRACP-5b was significantly elevated from the first week of treatment onwards. In vitro study, dexamethasone increased Dkk-1 mRNA expression in cultured NHOst, but sclerostin mRNA was not detected. Dexamethasone also increased Dkk-1 protein production by osteoblasts, whereas sclerostin protein was not detected. Bone formation might be impaired at least in the first week of the initiation of glucocorticoid therapy by increase of the serum Wnt signaling inhibitors; however, their reductions in the subsequent weeks were contradictory to the maintained suppression of the bone formation markers after glucocorticoid therapy for patients with systemic autoimmune diseases.

Predictive Value of Clinical Findings and Plasma Biomarkers after Fourteen Days of Prednisone Treatment for Acute Graft-versus-host Disease

We examined the hypothesis that plasma biomarkers and concomitant clinical findings after initial glucocorticoid therapy can accurately predict failure of graft-versus-host-disease (GVHD) treatment and mortality. We analyzed plasma samples and clinical data in 165 patients after 14 days of glucocorticoid therapy and used logistic regression and areas under receiver-operating characteristic curves (AUC) to evaluate associations with treatment failure and nonrelapse mortality (NRM). Initial treatment of GVHD was unsuccessful in 49 patients (30%). For predicting GVHD treatment failure, the best clinical combination (total serum bilirubin and skin GVHD stage: AUC, .70) was competitive with the best biomarker combination (T cell immunoglobulin and mucin domain 3 [TIM3] and [interleukin 1 receptor family encoded by the IL1RL1 gene, ST2]: AUC, .73). The combination of clinical features and biomarker results offered only a slight improvement (AUC, .75). For predicting NRM at 1 year, the best clinical predictor (total serum bilirubin: AUC, .81) was competitive with the best biomarker combination (TIM3 and soluble tumor necrosis factor receptor-1 [sTNFR1]: AUC, .85). The combination offered no improvement (AUC, .85). Infection was the proximate cause of death in virtually all patients. We conclude that after 14 days of glucocorticoid therapy, clinical findings (serum bilirubin, skin GVHD) and plasma biomarkers (TIM3, ST2, sTNFR1) can predict failure of GVHD treatment and NRM. These biomarkers reflect counter-regulatory mechanisms and provide insight into the pathophysiology of GVHD reactions after glucocorticoid treatment. The best predictive models, however, exhibit inadequate positive predictive values for identifying high-risk GVHD cohorts for investigational trials, as only a minority of patients with high-risk GVHD would be identified and most patients would be falsely predicted to have adverse outcomes.

Giant-Cell Arteritis: Do We Treat Patients with Large-Vessel Involvement Differently?

PurposeWe aimed to describe the initial treatment that was used in a common hospital-based practice in patients with giant-cell arteritis with and without large-vessel involvement at diagnosis as well as the outcomes in both groups. MethodsThis retrospective multi-center cohort included patients with giant-cell arteritis diagnosed between 2005 and 2015, all of whom had fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (FDG-PET/CT) performed at giant-cell arteritis diagnosis and were followed up for ≥12 months. We compared the features, treatment, and outcomes of patients with large-vessel involvement demonstrated on FDG-PET/CT with those of patients with a negative PET/CT. ResultsEighty patients (50 women, median age: 71 [53-87] years) were included, 40 of whom had large-vessel involvement demonstrated on FDG-PET/CT and 40 who did not. After a median 56-month follow-up time, 42 (53%) patients had discontinued glucocorticoid (GC) treatment. Patients with and without large-vessel involvement were indistinguishable in the initial median dose of prednisone (0.74 mg/kg vs 0.75 mg/kg, P = .56), overall GC duration (P = .77), GC discontinuation rate (P = .65), relapse rate (P = .50), frequency of GC-dependent disease requiring GC-sparing treatments (P = .62), and fatality rate (P = .06). ConclusionIn the setting of tertiary hospital recruitment, large-vessel involvement at giant-cell arteritis diagnosis using a PET/CT study had no influence on the choice of initial GC dose and had no impact on outcomes. Prospective studies are required to confirm these findings.

Does addition of glucocorticoids to the initial therapy influence the later course of the disease in patients with early RA? Results from the Swiss prospective observational registry (SCQM).

The main goal of this study was to analyse whether initial addition of glucocorticoid to DMARD therapy influences the long-term course of the disease in patients with early rheumatoid arthritis. All patients from the Swiss RA cohort SCQM with recent-onset arthritis (disease duration ≤1year) were analysed. The exposure of interest was the use of glucocorticoids (GCs) at baseline. As primary outcome, we considered clinical and radiographic disease progression, assessed by the disease activity (disease activity score, DAS-28), function (health assessment questionnaire disability index, HAQ-DI) and structural joint damage (Ratingen erosion score). The baseline disease characteristics were compared using standard descriptive statistics. The effects of initial GC use on disease progression during follow-up were estimated using linear mixed models with random slope and random intercept, adjusted for potential confounders. In total, 592 patients with early disease were available, with 4.3years of follow-up (average). Of these, 363 were initially treated with glucocorticoids (GC patients) and 228 were not (no-GC patients). DAS-28 (4.6 vs. 4.3, p=0.01) and the HAQ-DI (0.94 vs. 0.82, p=0.01) were higher at baseline in GC patients, while other prognostic factors were balanced at baseline. Neither the change of DAS-28, of HAQ-DI nor of the development of joint erosions differed between the two groups during follow-up. Escalation of treatment employing biologics was documented in 18.0% of the no-GC patients and 27.3% of the GC patients (p<0.01). In this cohort, patients with early RA initially treated with GCs had higher measures of disease activity at baseline in comparison to no-GC patients. Despite a similar course of the disease in GC versus non-GC patients, the higher escalation rate to biologic agents in GC patients may reflect a disease less responsive to therapy in these patients. These data suggest that GC use as part of the initial therapeutic strategy in early RA may prevent a more severe course of the disease in patients with higher clinical disease measures at the start of therapy.

Effects of immunosuppressive and biological agents on refractory Takayasu arteritis patients unresponsive to glucocorticoid treatment

BackgroundWe aimed to investigate the effects of immunosuppressive and biological agents on refractory Takayasu arteritis (TA) patients resistant to or dependent on glucocorticoids. MethodsForty-four consecutive TA patients were enrolled, and the clinical characteristics and effectiveness of the immunosuppressive and biological agents in achieving and maintaining remission among glucocorticoid-resistant or glucocorticoid-dependent patients were investigated. ResultsFifteen patients showed favorable response to the initial glucocorticoid treatment, and 29 patients exhibited resistance to initial glucocorticoid treatment or relapsed with tapering glucocorticoid. Of the 29 patients, 5 responded to additional glucocorticoid treatment, and 22 of the remaining 24 glucocorticoid-resistant or glucocorticoid-dependent patients were prescribed immunosuppressive agents. Methotrexate was the most commonly used in these patients as the first-line treatment. In total, 10 patients maintained remission using immunosuppressive agents, with the effectiveness of each agent about 20%. The only significant difference between patients who were and were not able to achieve and maintain remission with immunosuppressive agents was the presence of the HLA-B52 allele (p<0.0001). Biological agents were administered to 6 patients refractory to immunosuppressive agents. All patients were administered tumor necrosis factor (TNF) inhibitors as the first-line treatment, and 3 patients maintained remission. Anti-interleukin-6 receptor antibody was administered to 2 patients who were resistant to the TNF inhibitors, and 1 patient achieved and maintained remission. ConclusionIn our cohort, 64% of the glucocorticoid-resistant or glucocorticoid-dependent patients maintained remission through a combined treatment with glucocorticoid, immunosuppressive agents, and/or biological agents. The combined use of immunosuppressive and biological agents appears to be a promising treatment option for achieving and maintaining remission in refractory TA patients.

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against...

Recovery of renal function after glucocorticoid therapy for IgG4-related kidney disease with renal dysfunction.

BackgroundAlthough renal dysfunction in IgG4-related kidney disease (IgG4-RKD) shows rapid resolution with glucocorticoid therapy, little is known about the appropriate initial glucocorticoid dose for induction therapy or long-term renal outcome.MethodsWe retrospectively examined the differences in recovery of renal function according to the dose of glucocorticoid used for induction therapy and the long-term renal outcome in 43 patients with definite IgG4-RKD (mostly IgG4-tubulointerstitial nephritis), in whom the estimated glomerular filtration rate (eGFR) before glucocorticoid therapy was <60 ml/min.ResultsMost patients were treated with glucocorticoid alone and had been maintained on glucocorticoid. The initial dose of prednisolone employed was ≤0.6 mg/kg/day (mean 0.47) in 27 patients (group L), and >0.6 mg/kg/day (mean 0.81) in 16 patients (group H). In both groups, the pretreatment eGFR was significantly improved at 1 month after the start of glucocorticoid therapy and the degree of improvement showed no significant inter-group difference. Relapse of IgG4-RKD occurred in 16.7 % of the group L patients and 13.3 % of the group H patients (p = 0.78). Among 29 patients who were followed up for over 36 months (mean 74 months) and had been maintained on glucocorticoid, none showed progression to end-stage renal disease and there was no significant difference between eGFR at 1 month after treatment and eGFR at the last review.ConclusionIn glucocorticoid monotherapy for IgG4-RKD, a moderate dose is sufficient for induction, and recovery of renal function can be maintained for a long period on low-dose maintenance, although relapse can occur even in patients receiving maintenance therapy.