Initial Dose Of Prednisolone Research Articles

Clinical Characteristics and Treatment Outcomes of Patients With Newly Diagnosed Takayasu Arteritis in Japan During the First 2 Years of Treatment - A Nationwide Retrospective Cohort Study.

This study aimed to clarify recent clinical features and treatment outcomes in Japanese patients with newly diagnosed Takayasu arteritis (TAK) during the first 2 years of treatment. A nationwide multicenter retrospective cohort study for TAK was implemented to collect data between 2007 and 2014. The primary outcome of the study was clinical remission at Week 24. Of the 184 participants registered, 129 patients with newly diagnosed TAK were analyzed: 84% were female and the mean age at onset was 35 years. Clinical symptoms at diagnosis were mostly associated with large-vessel lesions. Frequent sites of vascular involvement included the carotid artery, subclavian artery, aortic arch, and descending aorta. The mean initial dose of prednisolone administered was 0.68 mg/kg/day, and 59% and 17% of patients received immunosuppressive drugs and biologics, respectively, by Week 104. Clinical remission at Week 24 and sustained clinical remission with daily prednisolone at ≤10 mg at Week 52 were achieved in 107 (82.9%) and 51 (39.5%) patients, respectively. The presence of signs and symptoms linked to large-vessel lesions was associated with failure to achieve sustained clinical remission at Week 52. We elucidated the clinical characteristics, treatment outcomes, and factors associated with failure to achieve sustained clinical remission in patients with newly diagnosed TAK in Japan during the first 2 years of treatment.

#1739 Combination rituximab & low-dose IV cyclophosphamide induction therapy for severe multi-system eosinophilic granulomatosis with polyangiitis

Abstract Background and Aims Current guidelines advise rituximab (RTX) or cyclophosphamide treatment for organ-threatening disease in eosinophilic granulomatosis with polyangiitis (EGPA). However, conventional treatment is often limited by partial efficacy, toxicity, high relapse rate and steroid dependency. We investigate the use of a combined RTX, low-dose cyclophosphamide, and steroid regimen for treatment of severe EGPA. Method Single-centre retrospective cohort study of patients treated with a combination induction regimen for severe EGPA (with kidney, cardiac or neurological involvement) between 2012-23. Data reported as median (±IQR) Results Eighteen patients (10 male; age 56 years [52-62]) are included. At treatment, BVAS was 16.3 [14-20], peak eosinophil count 9.3 × 109/L [5-13], C-reactive protein (CRP) 122 mg/L [80-193]. Eleven cases were ANCA positive (10 MPO-, 1 PR3-ANCA.) The proportions of patients affected by active/new respiratory, ENT, neurological, and gastrointestinal disease were 18/18 (100%), 14/18 (78%), 11/18 (61%), and 1/18 (6%), respectively. 11/18 (61%) had cardiac involvement (troponin 10345 ng/L [1240-7621]) and 6/18 (33%) had necrotising glomerulonephritis confirmed by renal biopsy (creatinine 123 µmol/L [83-167]). Cumulative cyclophosphamide dose was 3.5g [3.0-3.5] and total RTX dose was 2g. Initial prednisolone dose was 0.5-1.0 mg/kg/day, and this was rapidly weaned to 5 mg daily at a median time of 6.1 months [3.9-7.2], and 9/18 (50%) had steroids withdrawn completely by 11.7 months [4.6-20.6]. First-line maintenance treatment was azathioprine or MMF. By 6 months, all achieved disease remission as assessed by BVAS (all 0) and improved laboratory parameters: CRP 1 mg/L, eosinophil count 0.1 × 109/L, and ANCA testing negative. In those with renal disease, kidney function improved or stabilised in all (creatinine 95 µmol/L). In those with cardiac disease (11/18), magnetic resonance imaging was performed at baseline and at follow up (median time of 3.7 months) in all patients. Of these, 9/11 (82%) had oedema on initial scan and this improved in all cases; 10/11 (91%) had late gadolinium enhancement at baseline, which persisted in every case, though with significantly lower burden. The median follow-up period was 38 months [14-55]. At 1, 3 and 5 years, 100%, 92% and 76% of patients were in sustained remission (Fig. 1A). Three patients experienced relapse; one patient had major relapse with skin involvement requiring reinduction treatment; two patients had minor ENT relapse requiring retreatment with glucocorticoids. Infection-free survival at 1, 3 and 5 years was 94%, 78%, 62%, respectively (Fig. 1B). There were no deaths. Conclusion This regimen provided rapid disease control in patients with severe multi-system EGPA, including those with life-threatening cardiac manifestations, and enabled rapid glucocorticoid tapering and withdrawal. Disease-free remission was sustained during long-term follow up. Combination induction regimens may have a role in the treatment of organ-threatening disease in EGPA.

Outcomes of polymyalgia rheumatica in real-world practice: a longitudinal cohort study.

Background: Polymyalgia rheumatica (PMR) is an inflammatory condition closely linked with giant cell arteritis, which is a large vessel vasculitis. To provide real-world evidence on PMR outcomes and their determinants, we conducted a longitudinal study focusing on symptom relief and acute phase reactant normalization. Methods: We followed patients with PMR who were registered in Tabriz University of Medical Sciences Vasculitis Registry (TUOMS-VR) until February 2023. We measured sustained remission (primary outcome) and secondary outcomes including glucocorticoids (GCs)-free remission, medication-free remission, relapse rate and disease-induced damage. Results: We identified eighty-one patients with PMR and followed them for a median time of 57 months. In a median duration of 3 weeks, 98.8% of patients achieved symptom control, with 86.4% achieving sustained remission in a median duration of 9 weeks. Sustained remission was more common in non-smokers and adherent to therapy patients. Relapse occurred in 22.1% of patients, primarily due to non-adherence. Medication-free remission was observed in 30.9% of patients, especially among females and those with an initial prednisolone dose > 15 mg/d. Damage occurred in 42.0% of patients. Conclusion: Although sustained remission in PMR is not an unattainable goal in daily practice and most patients are in remission at the last visit, two-thirds of patients require long-term treatment.

Comparison of the therapeutic effects of 15 mg and 30 mg initial daily prednisolone doses in patients with subacute thyroiditis: a multicenter, randomized, open-label, parallel-controlled trial

Introduction Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We designed a randomized controlled trial (RCT) to compare the efficacy and safety of using a low initial dose of PSL with a standard initial dose of PSL in SAT patients. Patients and methods This open-label RCT was conducted at five hospitals in China from June 2019 to January 2022. SAT patients with moderate-to-severe pain or a poor response to non-steroidal anti-inflammatory drugs (NSAIDs) were randomly assigned in a 1:1 ratio to the experimental and control groups. The initial dose of PSL was 15 mg/d in the experimental group and 30 mg/d in the control group. The primary outcome was the total duration of PSL treatment, with non-inferiority prespecified with a margin of 7 days. Clinical trial registration number: ChiCTR1900023884. Results The full analysis set included 60 patients (30 in each group). The mean duration of PSL treatment in the experimental and control group was 34.62 ± 14.12 and 41.18 ± 16.89 days, respectively, meeting the non-inferiority criterion (pnon-inferiority = 0.0006). The total dose of PSL used in the experimental group was lower than in the control groups (330 vs 595 mg, p < 0.0001). There were no differences in the mean time to pain relief and complete resolution, the occurrence of recurrence, hypothyroidism, or adverse events between the groups. Conclusions The initial dose of 15 mg/d of PSL was not inferior to the dose of 30 mg/d in terms of efficacy and showed a similar safety profile. A low initial dose of PSL could be recommended for Chinese adult SAT patients who have a suboptimal response using NSAIDs or experience moderate-to-severe pain. KEY MESSAGES Low initial dose (15 mg/d) of prednisolone was non-inferior to the standard initial dose of prednisolone (30 mg/d) in treatment duration, time to pain relief, or the prevalence of hypothyroidism, recurrence, and adverse reactions in the treatment of subacute thyroiditis. Patients with subacute thyroiditis administered a low initial dose of prednisolone had a lower total dose of prednisolone compared to those receiving the standard dose of prednisolone.

OA15 Missing the wood(-y induration) for the trees

OA15 Missing the wood(-y induration) for the trees

Pathogenetic associations of anti-ribosomal P protein antibody titres and their subclasses in patients with systemic lupus erythematosus.

We evaluated the association between anti-ribosomal P antibody (anti-RibP) titres and disease activity in Japanese SLE patients. Eighty patients admitted and treated in Niigata University Hospital for new-onset or flare-up of SLE were included in this retrospective cross-sectional study. Clinical data were obtained from medical records at admission. The anti-RibP index, and cytokine and tryptophan metabolite levels were determined by ELISA. Of the 80 SLE patients, 30 had anti-RibP. Anti-RibP presence was associated with a greater prevalence of skin rash and more severe inflammatory responses, demonstrated by higher inflammatory cytokine levels, hypocomplementemia, and accelerated tryptophan metabolism, in younger patients. The serum anti-RibP index was correlated with age at diagnosis, clinical indicators, initial prednisolone dose, and cytokines and tryptophan metabolite levels in univariate analysis. Multivariate analysis showed that the anti-RibP index was independently associated with the initial prednisolone dose and the prevalence of skin rash. The anti-RibP IgGs were mainly the IgG2 and IgG3 subclasses, and anti-RibP IgG3 was associated with hypocomplementemia, higher DAS, accelerated kynurenine pathway activity, and higher proinflammatory cytokine production. The coexistence of anti-dsDNA IgG and anti-RibP IgG2 or IgG3 accompanied higher IL-10 and IFN-α2 levels; furthermore, anti-RibP IgG3 coexistence with anti-dsDNA antibody contributed to the requirement for higher initial prednisolone doses and accelerated kynurenine pathway activity. Anti-RibP was associated with clinical manifestations and parameters in SLE, and its index might be a useful indicator of disease severity. Anti-RibP IgG3 was the IgG subclass most strongly associated with the pathogenesis of SLE.

Effect of early initiation of steroid-sparing drugs in patients with bullous pemphigoid.

Bullous pemphigoid (BP) can be treated using systemic and topical glucocorticoids and/or other immunomodulatory agents. However, the long-term use of systemic glucocorticoids causes severe adverse side effects. This study was aimed at investigating whether the early initiation of corticosteroid-sparing therapy (CST) in BP patients results in better outcomes than late or no CST. We retrospectively identified all BP patients referred to the tertiary center, of the Department of Dermatology and Venerology, Aarhus University Hospital, Denmark, from 2015 to 2021. Patients' demographics, comorbidities, treatment, remission of BP, length of admission, relapse, and 1-year mortality were recorded. All patients who received CST were dichotomised into two groups: initiated with CST <28 or >28 days. The groups were compared using t-tests. Additionally, all patients who received CST were compared with those who received systemic glucocorticoids alone. Our cohort was compared with that of a previous study (2006-2013) performed in our department. In 2015, we revised our BP treatment guidelines to include the early initiation of CST. On comparing the group of patients initiated with CST <28 versus >28 days, we found no significant differences in the complications or mortality between the groups (p = 0.63 and p=0.79, respectively). The <28 days group had a lower rate of relapse (p < 0.05). On comparing data from this study with those from the previous study, conducted before we revised our treatment guideline, we found a reduced initial dose of prednisolone and reduced admission time in this study. No significant differences were found between patients treated with CST and those treated with systemic glucocorticoids alone. The rate of complications and 1-year mortality did not differ significantly between the two subgroups in this study. The relapse rate was lower in the CST <28 days group than in the CST >28 days group. The initial dose of prednisolone and admission time were reduced in this study compared with those in the previous study performed before the implementation of a local treatment guideline recommending the early initiation of CST.

Chemoprophylaxis against Pneumocystis jirovecii pneumonia in Japanese patients with ANCA-associated vasculitis: an observational study.

This study investigated the current practice of prophylactic treatment against PCP (Pneumocystis jirovecii) and its effectiveness in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). This study included 319 patients registered from 53 institutions in Japan and newly diagnosed with AAV. During the 2-year observation period, we examined the frequency of usage, effectiveness and safety of prophylactic drugs against PCP. Most patients received prophylactic drugs against PCP with the initiation of immunosuppressive agents, and >50% of these remained on chemoprophylaxis against PCP at 2 years after. The initial daily dose of oral prednisolone and proportion of cyclophosphamide administration were higher in patients who received chemoprophylaxis against PCP than in those who did not. PCP occurred in nine patients (3%) and resulted in the death of four. The incidence rate of PCP in patients who received chemoprophylaxis was 1.13/100 patient-years (95% confidence interval, 0.38-2.68) and that in those who did not was 2.74 (1.04-6.02). The incidence rate ratio was 0.41 (0.11-1.53). The markedly low incidence of PCP may be attributed to the continuous chemoprophylaxis against PCP received by >50% of Japanese patients with AAV, though the effectiveness of chemoprophylaxis against PCP was not statistically confirmed.

Identifying the Lowest Effective Initial Dose of Prednisolone for the Treatment of Subacute Granulomatous Thyroiditis: A Systematic Review and Meta-Analysis.

Subacute granulomatous thyroiditis (SAGT) is an inflammatory disease due to viral infections. Glucocorticoids, especially prednisolone (PSL), are one of the first approaches in the treatment of patients with SAGT. To date, no study has determined the lowest effective dose of prednisolone with the lowest recurrence rate in the treatment of SAGT. This study aimed to use meta-analysis methods to identify the appropriate dosage of prednisolone with the lowest recurrence rate in the treatment of patients with SAGT. This study was conducted according to the PRISMA checklist in February 2021. Two independent researchers performed a search for relevant literature published before March 2021 in English databases, including Scopus, MEDLINE (via PubMed), Web of Science, Cochrane Library, Google Scholar, EMBASE, and also Persian electronic databases including SID, Iran medex, Magiran, and Irandoc. The search algorithm was initially developed by using a combination of MeSH terms, keywords, and also Boolean operators ("AND"; "OR"; "NOT"): Subacute thyroiditis, De Quervain Thyroiditis, Glucocorticoids, Prednisolone, Recurrence, and Meta-Analysis. All statistical analyses were performed using STATA 15.0 (StataCorp LLC, College Station, TX, USA) and SPSS 17.0. A random-effects model based on Metaprop was applied for the Meta-analysis. To assess heterogeneity between studies, the chi-squared test and I2 index were used, and for evaluating publication bias, funnel plots and Egger tests were performed. The overall recurrence rate was 14.72% [95% CI: 9.63- 20.58] and there was a significant heterogeneity among the studies [I2 = 69.56%; P=0.000]. To evaluate the lowest effective dose of prednisolone, we divided the studies into two groups based on the mean initial dose of prednisolone: less than or equal to 20 mg/day (group one) and greater than 20 mg/day (group two). The recurrence rate in group 1 was 11% [95% CI: 5.7- 16.2] and in group 2 was 23.6% [95% CI: 11.5- 35.6]. Significant correlations were observed between the initial mean dose of PSL and recurrence rate (r= 0.71; P= 0.013). Begg's funnel plot had no evidence of publication bias in these studies (p=0.160). According to the results of this meta-analysis, 15 to 20 mg/day of prednisolone is the most effective dosage with the lowest recurrence rate in the treatment of subacute Granulomatous thyroiditis.

P026 Sugar rush: single-centre audit of screening and counselling for steroid-induced hyperglycaemia, based on the British Society for Rheumatology giant cell arteritis guideline

Abstract Background/Aims In patients starting steroids for giant cell arteritis (GCA), to evaluate adherence to BSR guideline: HbA1c monitoring, documentation of counselling, and detection of steroid-induced hyperglycaemia. Methods Data were gathered from the electronic medical records. Steroid-induced hyperglycaemia was defined as new HbA1c &amp;gt;48 measured 3+ months after beginning steroid treatment. The data were presented at a regional meeting to raise awareness and encourage clinicians to incorporate counselling and monitoring into their practice, and a GCA clinic was set up. Practice was then re-evaluated. Results In the baseline dataset, 60 patients with GCA had a mean age of 72; 47 were female; mean body mass index (BMI) was 27 (for the 39/60 with a recorded height and weight). Mean initial dose of prednisolone was 45.9mg. The re-audit cohort were comparable with a mean age of 73.1; 19 females and mean BMI of 27 (for 15/30 with recorded). Mean initial prednisolone dose of 46.3mg. Baseline HbA1c was checked in 32/60 (53%) initially, and 28/30 (93%) on re-audit. 7/60 (12%) had documentation of counselling for steroid-induced hyperglycaemia initially, which increased to 9/30 (30%) on re-audit. Hyperglycaemia was detected in 8/60 (13%) of the initial audit group, compared to 11/30 (36%) in the re-audit. In the initial cohort, 3/10 (30%) of those with diabetes at baseline developed hyperglycaemia and 4/12 (33%) of those with pre-diabetes at baseline developed hyperglycaemia. In the re-audit, 7/9 (78%) of those with diabetes at baseline developed hyperglycaemia and 4/7 (57%) with pre-diabetes at baseline developed hyperglycaemia. Those who developed hyperglycaemia had a higher baseline weight and BMI (Table 1) in both the initial cohort and re-audit. Conclusion The intervention improved monitoring for steroid-induced hyperglycaemia, improving detection rates. We identified patient counselling as a priority for future improvement work. Disclosure L.J. Blackmore: None. K.L. Devine: None. S.L. Mackie: Consultancies; On behalf of University of Leeds for AbbVie, AstraZeneca, Sanofi, Roche. Other; Support from Roche to attend EULAR2019.

Treatment and Outcome of Autoimmune Hepatitis (AIH): Audit of 28 UK centres.

With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities. Patients with AIH were identified in 14 University and 14 District General hospitals; incident cases during 2007-2015 and prevalent cases, presenting 2000-2015. Treatment and outcomes were analysed. In 1267 patients with AIH, followed-up for 3.8(0-15) years, 5- and 10-year death/transplant rates were 7.1+0.8% and 10.1+1.3% (all-cause) and 4.0+0.6% and 5.9+1% (liver-related) respectively. Baseline parameters independently associated with death/transplantation for all-causes were: older age, vascular/respiratory co-morbidity, cirrhosis, decompensation, platelet count, attending transplant centre and for liver-related: the last four of these and peak bilirubin All-cause and liver-related death/transplantation was independently associated with: non-treatment with corticosteroids, non-treatment with a steroid-sparing agent (SSA), non-treatment of asymptomatic or non-cirrhotic patients and initial dose of Prednisolone >35mg/0.5mg/kg/day (all-cause only), but not with type of steroid (Prednisolone versus Budesonide) or steroid duration beyond 12-months. Subsequent all-cause and liver-death/transplant rates showed independent associations with smaller percentage fall in serum ALT after 1 and 3-months, but not with failure to normalise levels over 12-months. We observed higher death/transplant rates in patients with AIH who were untreated with steroids (including asymptomatic or non-cirrhotic sub-groups), those receiving higher Prednisolone doses and those who did not receive an SSA. Similar death/transplant rates were seen in those receiving Prednisolone or Budesonide, those continuing steroids after 12-months and patients attaining normal ALT within 12-months versus not.

THE USE OF LOW DOSE PREDNISOLONE IN PATIENTS WITH SUBACUTE THYROIDITIS AND ITS EFFECT ON IMPAIRED LIFE AND SLEEP QUALITY.

Subacute thyroiditis is an inflammatory thyroid disease, which is treated by nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids. Defining characteristics of patients with subacute thyroiditis at diagnosis and during follow-up. Investigating the efficacies of NSAID and different doses of steroids and their effects on rates of relapse, recurrence, development of hypothyroidism and on quality of life and sleep parameters. A 3-year observational study in a tertiary referral center. A total of 63 patients with subacute thyroiditis were included. Clinical outcomes of patients treated with NSAIDs and NSAID unresponsive patients treated with prednisolone with initial doses of 0.5 mg/kg/day and 15 mg/day were evaluated. White blood cell count at diagnosis was an independent predictor of NSAID unresponsiveness. No relapse or recurrence was observed in patients receiving low dose of steroids. Long symptom duration until diagnosis and treatment with NSAIDs were associated with development of hypothyroidism. Subacute thyroiditis caused significant deterioration in quality of life and sleep of patients and low dose of steroid was as effective as higher doses in improving these parameters. For patients with no response to NSAID therapy, an initial low dose of prednisolone (15 mg/day) is determined as a safe treatment method when dose reduction is performed with appropriate timing.

Association of initial prednisolone dose with remission, relapse, and infectious complications in adult-onset minimal change disease

BackgroundA dose of 0.5–1 mg/kg/day of prednisolone (PSL) is administered for the initial treatment of minimal change disease (MCD). However, little is known about the optimal PSL dose for the initial treatment of MCD.MethodsWe conducted a retrospective multicenter cohort study of treatment-naive adult patients with MCD diagnosed by renal biopsy from 1981 to 2015 in whom PSL monotherapy was performed as the initial treatment. The exposure of interest was an initial median PSL dose of < 0.63 mg/kg/day (Group L) compared to ≥ 0.63 mg/kg/day (Group H). Cumulative remission and relapse after remission were compared between these groups using Cox regression adjusted for baseline characteristics.ResultsNinety-one patients met the inclusion criteria. During a median follow-up of 2.98 years, 87 (95.6%) patients achieved complete remission, and 47.1% relapsed after remission. There was no significant difference in the remission rate between the groups at 4 weeks of follow-up (66.7 vs. 82.6%). The median time to remission in Group L was comparable to that in Group H (17.0 vs. 14.0 days). A multivariable Cox hazard model revealed that the initial PSL dose was not a significant predictor of remission. The cumulative steroid doses at 6 months, 1 year, and 2 years after treatment initiation were significantly lower in Group L than in Group H.ConclusionThe initial PSL dose was not associated with time to remission, remission rate, time to relapse, or relapse rate. Therefore, a low initial steroid dose may be sufficient to achieve remission.

Drug reaction with eosinophilia and systemic symptoms: A single center descriptive observational study.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse cutaneous drug reaction with mortality up to 10%. It is a rare condition with risk varying between 1 in 1000 and 1 in 10 000 drug exposures. The aim of the study was to describe clinical features, management and drugs responsible for causing DRESS. The study was retrospective, observational study. The data of patients admitted to hospital with diagnosis of DRESS during study period (March 2018 to February 2020), were retrieved and analyzed. The descriptive data of patients were summarized. The continuous variables were summarized as mean ± SD and/or median, depending on the skewness of the data. The categorical variables were expressed as absolute numbers, frequency, and proportions (%). The data was tabulated and analyzed in Microsoft Excel 2019 version. A total of 20 patients who met inclusion criteria (probable or definite DRESS as per RegiSCAR criteria) were included in the study. The mean age of the patients was 41.2 ± 15.7 years. The average latency period was 26.45 ± 5.65 days (range: 7-60). The commonest culprit drugs were dapsone and phenytoin, each in five (25%) patients. Commonest morphology of rash was morbilliform in 13 (65%) patients. One patient with targetoid rash had multi-organ involvement. Facial edema, periorbital edema, and conjunctival injection were seen in 17 (85%), seven (35%), and six (30%) cases, respectively. Eosinophilia was present in 18 (90%) patients with mean (±SD) value of 1976 ± 840 cells/μl. Liver was the commonest internal organ involved in 14 (70%) patients and kidney in three (15%) patients. The initial dose of prednisolone for treatment varied from 0.75 to 2 mg/kg/day. The mean duration of steroid treatment was 64 ± 21 days. Two patients were treated with intravenous methylprednisolone and one with intravenous immunoglobulin. Two patients (10%) had recurrence of adverse drug reaction >6 months after completion of initial treatment and two (10%) developed autoimmune thyroiditis during follow-up. Small sample size and retrospective nature of the study were main limitations. Selection bias is a possibility as study was carried out in tertiary care center. Tests for incriminating culprit drugs such as patch test, intradermal test, and lymphocyte transformation test were not performed. DRESS is a rare disease that can be diagnosed early with high index of suspicion and treated successfully with steroids. The internal organ involvement is common in DRESS and requires a thorough evaluation.

Association between mortality and cytomegalovirus reactivation during remission induction therapy in patients with rheumatic diseases.

To elucidate the characteristics of patients with rheumatic diseases with cytomegalovirus (CMV) reactivation. In our study, we consecutively reviewed patients with rheumatic diseases who received remission induction therapy in our institution from January 2012 to March 2016 and enrolled the patients who were evaluated about CMV infection. CMV reactivation was characterised by the detection of polymorphonuclear leukocytes with CMV pp65. The characteristics and clinical courses of the patients with CMV reactivation were compared to those without CMV. We observed CMV reactivation in 71 (39.7%, CMV-positive group) out of 179 patients. Age (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.002-1.044, p=0.03), lymphocyte counts (OR 0.999, 95% CI 0.999-1.000, p=0.03), and initial prednisolone dose (OR 18.596, 95% CI 2.399-144.157, p<0.01) were considered as independent relevant risk factors for CMV reactivation. Patients in the CMV-positive group showed significantly higher incidences of all infections (48%) and severe infections (31%) than those in the CMV-negative group (48% vs .31%, p=0.037; 31% vs. 6%, p<0.001, respectively). Higher mortality was observed in the CMV-positive group than in the CMV-negative group (14.1% vs. 1.9%). The lymphocyte counts were more relevant to CMV infection and mortality than were the serum IgG levels. Our study revealed that CMV reactivation occurred in one third of all patients with rheumatic diseases who were undergoing intensive remission induction therapy, and it was found to be relevant to other severe infections and infection-related deaths.

The efficacy of methotrexate for intolerance to prednisolone therapy in cardiac sarcoidosis

Abstract Background and purpose Fluorine-18-flurodeoxyglucose positron emission tomography (18FDG-PET) is a useful examination assessing active inflammatory myocardium noninvasively in patients with cardiac sarcoidosis (CS). Though immunosuppression like prednisolone (PSL) and Methotrexate (MTX) as alternative therapy is used to suppress the inflammation, little is known about the rate of response and efficacy of MTX for intolerance to PSL therapy. Methods From Aug 2016, we prospectively enrolled CS with positively accumulated of FDG in the heart. The initial dose of PSL was 30mg/day, wherefrom the dose was tapered down 5mg/month until 6 months. After 6 months, follow-up 18FDG-PET was performed. Using 18FDG-PET images, we calculated total lesion glycolysis (TLG; SUVmeam x metabolic volume) and calculated the reduction rate of TLG. In order to estimate the response rate to PSL therapy, responder group (R-group) was defined as TLG reduction rate ≥70% and poor-responder group (PR-group) was defined as TLG reduction rate &amp;lt;70% after PSL therapy. After prescribed PSL, subjects with PR-group randomized to PSL (maximum dose 30mg daily and tapered down 5mg/month until 6 months) or to MTX (6mg weekly). Results In 64 CS patients, 55 patients had serial 18FDG-PET before and 6 months after PSL therapy. 18FDG-PET images were acquired following 7 day's carbohydrate limitation and after at least 18-h fasting (mean free fatty acid level right before 18FDG-PET acquisition was 1.05 mEq/L). The mean age was 63.4 years old and 42 (76.4%) patients were female. Because of 6 months PSL therapy, even though there were no significant difference in BNP (from 59.9 (26.2–137.6) to 60.4 (18.5–122.0) (P=0.593), LV-Dd (from 50.9 (44.5–59.5) to 49.7 (45.5–61.3) (P=0.666) and LV-EF (from 49.5 (34.4–62.5) to 49.9 (38.0–62.0) (P=0.792) at pre and post therapy, respectively, TLG were detected significant reduction from 216.4 (74.2–411.6) to 0.8 (0.0–8.2), (p&amp;lt;0.001). In response to PSL therapy, 47 (85.5%) CS patients were classified to R-group and 8 (14.5%) were classified to PR-group. Furthermore, when performed block randomization and divide 8 PR-group patients into MTX (n=3) and re-increased PSL (n=5) for more 6 months, MTX group is prone to high rate of TLG reduction than re-increased PSL-group (89.4% vs 59.9%) and one patient belonged to re-increased PSL group showed that the further elevation of TLG level at additional 6-months PSL therapy (349⇒483) (Figure). Conclusions 1) By immunosuppression therapy using PSL for CS, about 86% patients showed significant reduction of myocardial FDG accumulation. 2) When detected intolerance for PSL therapy, MTX might be effective for reduction of inflammation of sarcoidosis in the heart, which might be effective as an alternate therapy in CS. The TLG level after randomization Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Grant-in-aid for scientific research

Effect of prednisolone therapy on serum levels of 1,2-O-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester lipase in dogs.

BackgroundActivity of 1,2‐O‐dilauryl‐rac‐glycero glutaric acid‐(6′‐methylresorufin) ester (DGGR) lipase in serum shows good agreement with pancreatic lipase (cPL) in dogs. Although prednisolone therapy does not seem to affect serum cPL concentration, its influence on DGGR lipase is unclear.ObjectivesThe aim of the study was to evaluate the effect of prednisolone therapy on DGGR lipase serum activity in dogs.AnimalsThirty‐four dogs were used, of which 17 dogs received prednisolone (study group) and 17 healthy dogs did not receive treatment.MethodsA prospective cohort study measured DGGR lipase activity in both groups at 3 time points: T0, T1, and T2, corresponding to days 0, 7‐10, and 21‐30, respectively. Dogs from study group presented a medical reason that justified the use of prednisolone for at least 3 weeks. Initial prednisolone dose was .5‐2.0 mg/kg/day PO with a reduction at T1 to a final dose that was maintained until T2. DGGR lipase activity >160 U/L was defined as clinically relevant.ResultsIn the study group, DGGR lipase activity increased significantly from T0 to T1 (P = .02) and decreased significantly from T1 to T2 (P = .02). Median DGGR activity at each time point (T0, T1, and T2) was 24.74 (14.45–31.48), 36.82 (23.8–80.16), and 29.52 (15.91–48.48) U/L, respectively. In the control group, no significant changes were observed over time (P = .93). The DGGR lipase activity and prednisolone doses were not correlated for both T0‐T1 (r s = .371, P = .14) and T1‐T2 (r s = 0.390, P = .12).Conclusion and Clinical ImportanceDGGR lipase activity was affected by prednisolone administered orally in dogs. However, this variation was not clinically important as values remained below the relevant upper limit.

Epidemiology and Factors Associated with Remission of Pemphigus Vulgaris and Foliaceus in Singapore

Pemphigus is a chronic, relapsing immunobullous disease. There is limited data on the clinical course and prognostic factors of pemphigus in Asian patients. We conducted a retrospective cohort study of all newly diagnosed pemphigus vulgaris (PV) and pemphigus foliaceus (PF) patients seen at the National Skin Centre from 1 January 2004 to 31 December 2009. Demographic and clinical data on comorbidities, treatment and remission were recorded. Mortality information was obtained from the National Registry of Diseases. Prognostic endpoint was overall remission at last visit. Sixty- one patients (36 PV and 25 PF) were recruited. Among PV patients, higher initial prednisolone dose (P = 0.017) and the use of azathioprine (P = 0.028) were significantly associated with overall remission at last visit. However, higher desmoglein 1 antibody titres at diagnosis (P = 0.024) and the use of dapsone (P = 0.008) were negatively associated with overall remission at last visit. Among PF patients, only higher desmoglein 1 antibody titre at diagnosis (P = 0.041) was found to be associated with lower overall remission at last visit. There was no mortality during the 3-year follow-up period in both PV and PF. Higher initial prednisolone dose and the use of azathioprine in PV desmoglein 1 antibody titre at diagnosis in PV and PF might be prognostic markers for achieving remission. Use of dapsone was associated with lower overall remission in PV, but this might be confounded because dapsone was used as an adjuvant therapy in recalcitrant cases. Owing to study methodology and limitations, further evaluation is needed for better prognostication of pemphigus.

Retrospective analysis of infliximab and adalimumab treatment in a large cohort of juvenile dermatomyositis patients

BackgroundAnti-TNF treatment may be useful for the treatment of patients with refractory juvenile dermatomyositis (JDM). The aim of this study was to describe the use of infliximab and adalimumab therapy in juvenile dermatomyositis as an adjunctive treatment.MethodsSixty children recruited to the UK JDM Cohort and Biomarker Study that had received at least 3 months of anti-TNF treatment (infliximab or adalimumab) were studied. Childhood Myositis Assessment Scale (CMAS), Manual Muscle Testing (MMT8) and physician’s global assessment (PGA) were recorded. Skin disease was assessed using the modified skin disease activity score (DAS). Data were analysed using Friedman’s test for repeated measures analysis of variance.ResultsCompared to baseline, there were improvements at 6 and 12 months in skin disease (χ2(2) = 15.52, p = 0.00043), global disease (χ2(2) = 8.14, p = 0.017) and muscle disease (CMAS χ2(2) = 17.02, p = 0.0002 and MMT χ2(2) = 10.56, p = 0.005) in infliximab patients. For patients who switched from infliximab to adalimumab, there was improvement in global disease activity (χ2(2) = 6.73, p = 0.03), and trends towards improvement in CMAS, MMT8 and modified DAS. The median initial prednisolone dose was 6 [0–10] mg, and final was 2.5 [0–7.5] mg (p < 0.0001). Fifty-four per cent of patients had a reduction in the number and/or size of calcinosis lesions. Twenty-five per cent switched their anti-TNF treatment from infliximab to adalimumab. 66.7%of the switches were to improve disease control, 26.7% due to adverse events and 6.6% due to patient preference. A total of 13.9 adverse reactions occurred in 100 patient-years, of which 5.7 were considered serious.ConclusionReductions in muscle and skin disease, including calcinosis, were seen following treatment with infliximab and adalimumab.

Associated factors of poor treatment outcomes in patients with giant cell arteritis: clinical implication of large vessel lesions

BackgroundRelapses frequently occur in giant cell arteritis (GCA), and long-term glucocorticoid therapy is required. The identification of associated factors with poor treatment outcomes is important to decide the treatment algorithm of GCA.MethodsWe enrolled 139 newly diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed with temporal artery biopsy, 1990 American College of Rheumatology classification criteria, or large vessel lesions (LVLs) detected by imaging based on the modified classification criteria. Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 52 weeks) were evaluated. Clinical remission was defined as the absence of clinical signs and symptoms in cranial and large vessel areas, polymyalgia rheumatica (PMR), and elevation of C-reactive protein (CRP) levels. A patient was determined to have a relapse if he/she had either one of the signs and symptoms that newly appeared or worsened after achieving clinical remission. Re-elevation of CRP without clinical manifestations was considered as a relapse if other causes such as infection were excluded and the treatment was intensified. Associated factors with poor treatment outcomes were analyzed by using the Cox proportional hazard model.ResultsCranial lesions, PMR, and LVLs were detected in 77.7%, 41.7%, and 52.5% of the enrolled patients, respectively. Treatment outcomes were evaluated in 119 newly diagnosed patients who were observed for 24 weeks or longer. The mean initial dose of prednisolone was 0.76 mg/kg/day, and 29.4% received any concomitant immunosuppressive drugs at baseline. Overall, 41 (34.5%) of the 119 patients had poor treatment outcomes; 13 did not achieve clinical remission by week 24, and 28 had a relapse after achieving clinical remission. Cumulative rates of the events of poor treatment outcomes in patients with and without LVLs were 47.5% and 17.7%, respectively. A multivariable model showed the presence of LVLs at baseline was significantly associated with poor treatment outcomes (adjusted hazard ratio [HR] 3.54, 95% CI 1.52–8.24, p = 0.003). Cranial lesions and PMR did not increase the risk of poor treatment outcomes.ConclusionThe initial treatment intensity in the treatment algorithm of GCA could be determined based upon the presence or absence of LVLs detected by imaging at baseline.