Reduction Of Glucocorticoid Dose Research Articles

A case of IgG4-related disease associated with ulcerative colitis that was successfully treated with a JAK inhibitor.

Glucocorticoids (GC) are the standard of care for the induction and maintenance of remission in immunoglobulin G4 (IgG4)-related diseases. However, IgG4-related diseases often relapse with GC dose reduction, not only making GC dose reduction difficult but also necessitating GC dose escalation in many cases. Therefore, other immunosuppressive drugs are required to maintain remission. Here, we report a 39-year-old man with ulcerative colitis and IgG4-related disease who experienced a relapse of both diseases despite treatment with tacrolimus and 6-mercaptopurine. Following the initiation of tofacitinib, a Janus-associated kinase inhibitor, it was possible to reduce the GC dose while maintaining remission of both diseases. This case highlights the potential utility of Janus-associated kinase inhibitors in managing complex cases of IgG4-related disease, especially those with concurrent conditions such as ulcerative colitis.

Comparison of methotrexate and azathioprine as the first-line steroid-sparing immunosuppressive agents in patients with Takayasu's arteritis

BackgroundImmunosuppressive (IS) agents are recommended for the first-line treatment of patients with active Takayasu's arteritis (TAK) together with glucocorticoids (GCs). However, there is limited data comparing the efficacy and outcomes of different IS agents for this purpose. ObjectivesIn this study, we aimed to compare the outcomes of two most frequently used first-line IS agents, namely methotrexate (MTX) and azathioprine (AZA) in TAK patients. MethodsTAK patients who received any IS agent in addition to GCs as the initial therapy were included in this multicentre, retrospective cohort study. Clinical, laboratory and imaging data of the patients were assessed. In addition, a matched analysis (cc match) using variables ‘age’, ‘gender’ and ‘diffuse aortic involvement’ was performed between patients who received MTX or AZA as the first-line IS treatment. ResultsWe recruited 301 patients (F/M: 260/41, mean age: 42.2 ± 13.3 years) from 10 tertiary centres. As the first-line IS agent, 204 (67.8 %) patients received MTX, and 77 (25.6 %) received AZA. Less frequently used IS agents included cyclophosphamide in 17 (5.6 %), leflunomide in 2 (0.5 %) and mycophenolate mofetil in one patient. The remission, relapse, radiographic progression and adverse effect rates were similar between patients who received MTX and AZA as the first-line IS agent. Vascular surgery rate was significantly higher in the AZA group (23% vs. 9 %, p = 0.001), whereas the frequency of patients receiving ≤5 mg/day GCs at the end of the follow-up was significantly higher in the MTX group (76% vs 62 %, p = 0.034). Similarly, the rate of vascular surgery was higher in AZA group in matched analysis. Drug survival was similar between MTX and AZA groups (median 48 months, MTX vs AZA: 32% vs 42 %, p = 0.34). IS therapy was discontinued in 18 (12 MTX, 6 AZA) patients during the follow-up period due to remission. Among those patients, two patients had a relapse at 2 and 6 months, while 16 patients were still on remission at the end of a mean 69.4 (±50.9) months of follow-up. ConclusionsRemission, relapse, radiographic progression and drug survival rates of AZA and MTX were similar for patients with TAK receiving an IS agent as the first-line f therapy. The rate of vascular surgery was higher and the rate of GC dose reduction was lower with AZA compared to MTX at the end of the follow-up.

Long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha treatment for patients with Behcet's uveitis: A systematic review and meta-analysis.

This study aims to evaluate the long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha (anti-TNF-α) therapy for patients with Behcet's uveitis (BU) using meta-analysis. We searched the Web of Science and PubMed databases for eligible studies up to December 1, 2022. The quality of each identified study was assessed using the Joanna Briggs Institute's case series literature quality assessment tool. Statistical analysis was conducted using Stata 16.0 software with a random-effects model. Twelve studies comprising 1156 patients with BU were included in our analysis. We found that 85.0% of patients achieved ocular inflammation remission after receiving anti-TNF-α treatment, with a 95% confidence interval (CI) ranging from 78.7% to 90.5%. Additionally, 77.4% (95% CI: 57.5%-92.5%) experienced an improvement in visual acuity (VA). Moreover, the pooled dose reduction of glucocorticoids (GCs) was 11.08 mg (95% CI: -13.34 mg to -8.83 mg). Throughout the follow-up period, the cumulative retention rate of the medication was 67.3% (95% CI: 53.7%-79.6%). Serious adverse events occurred in 5.8% (95% CI: 3.1%-8.9%) of cases, with the three most common types being severe infusion or injection reactions (2.7%; 95% CI: 0.8%-5.4%), tuberculosis (1.3%; 95% CI: 0.0%-3.9%), and bacterial pneumonia (1.3%; 95% CI: 0.1%-3.4%). Subgroup analysis revealed that ocular inflammation remission rates were 89.3% (95% CI: 81.2%-95.5%) for adalimumab treatment and 83.7% (95% CI: 75.3%-90.8%) for infliximab treatment. The drug retention rate after adalimumab therapy was 70.3% (95% CI: 62.0%-78.0%) compared to 66.4% (95% CI: 48.6%-82.2%) for infliximab treatment. Furthermore, the incidence of severe infusion or injection reactions was 2.2% (95% CI: 0.1%-5.8%) following adalimumab treatment and 3.5% (95% CI: 0.7%-7.7%) following infliximab treatment. Anti-TNF-α therapy represents an effective treatment for BU patients with favorable safety profile and high drug retention rate and a potential advantage of adalimumab over infliximab in terms of ocular inflammation remission, drug retention, and the incidence of severe infusion or injection reactions.

Telitacicept in patients with active systemic lupus erythematosus: results of a phase 2b, randomised, double-blind, placebo-controlled trial

ObjectivesThis phase 2b, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of telitacicept, a novel fusion protein that neutralises signals of B lymphocyte stimulator and a proliferation-inducing ligand, in...

Glucocorticoid reduction induced chorea in pediatric-onset systemic lupus erythematosus: A case report

BACKGROUND Pediatric-onset systemic lupus erythematosus (SLE) is typically more severe than adult-onset SLE, with a higher incidence of nervous system involvement. Chorea is a relatively rare neurological complication reported in 2.4%-7% of SLE patients. In particular, chorea induced by glucocorticoid dose reduction is even rarer. Herein, we report the case of a girl with SLE, who developed chorea during the process of glucocorticoid therapy reduction. CASE SUMMARY We describe a 14-year-old girl who was diagnosed with SLE. She was treated with methylprednisolone and rituximab, and her symptoms improved. On the second day after the methylprednisolone dose was reduced according to the treatment guidelines, the patient developed chorea. Her condition improved after adjusting her glucocorticoid regimen. CONCLUSION This case is a reminder that extra attention to chorea is required in SLE patients during glucocorticoid dose reduction.

Disease modification achievement in patients with lupus nephritis in a real-life setting: mission impossible?

ObjectiveA preliminary definition of disease modification (DM) in lupus nephritis (LN) was recently developed focusing on long-term remission and damage prevention, with minimal treatment-associated toxicity. We aimed to further specify...

Clinical Images: Optic perineuritis in relapsing granulomatosis with polyangiitis.

The patient, a 76-year-old man who was previously diagnosed as having granulomatosis with polyangiitis (GPA) and was receiving rituximab maintenance therapy every 6 months, presented with malaise, night sweat, transient lockjaw, and right-sided facial pain and swelling following dental extraction 2 weeks earlier. He subsequently developed retrobulbar pain, conjunctival injection, chemosis, and fluctuating visual impairment. T1-weighted contrast magnetic resonance imaging (MRI) of the orbit revealed contrast enhancement of the right optic nerve sheath sparing the optic nerve itself (“doughnut sign”) consistent with optic perineuritis (coronal image in A; axial image in B). Laboratory evaluation showed elevated C-reactive protein (276 mg/liter) and leukocytosis (13,430/μl) (Supplementary Table 1, http://onlinelibrary.wiley.com/doi/10.1002/art.42426). Blood cultures and cerebrospinal fluid analysis including mycobacterial and fungal polymerase chain reaction showed no evidence of infection. Moreover, empirical antibiotic therapy did not result in clinical improvement. In GPA, optic neuropathy accompanied by retrobulbar pain and/or oculomotor nerve palsy usually occurs as a result of compression by inflammatory orbital masses (1, 2). However, it may rarely be encountered due to posterior ischemic neuropathy, optic neuritis, and/or perineuritis without inflammatory pseudotumor (1). Imaging may reveal signs of pachymeningitis, often subtle, and additional orbital apex infiltration (1-3). In some patients, high levels of inflammation markers can be detected (1, 2). Optic perineuritis has a poor prognosis with frequent recurrence of symptoms following reduction of glucocorticoid dose, thus requiring aggressive immunosuppressive treatment with cyclophosphamide and/or rituximab (1, 2). In our patient, immunosuppressive therapy was switched to combined rituximab and pulse cyclophosphamide treatment with the addition of a glucocorticoid for the re-induction of remission, resulting in protracted resolution of clinical symptoms and MRI findings (Supplementary Figure 1, http://onlinelibrary.wiley.com/doi/10.1002/art.42426). Disclosure Form Supplementary Figure 1: MRI follow-up showing resolution of contrast enhancement of the right optic nerve sheath following re-induction of remission with combined rituximab and pulse cyclophosphamide treatment and addition of glucocorticoid (A coronal image, B axial image). Supplementary Table 1: Laboratory values Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Topical glucocorticoid application causing iatrogenic Cushing’s syndrome followed by secondary adrenal insufficiency in infants: two case reports

BackgroundIatrogenic Cushing’s syndrome induced by oral and parenteral glucocorticoid administration is a well-known complication. Immediate withdrawal from exogenous steroids can lead to life-threatening adrenal insufficiency. However, Cushing’s syndrome caused by topical treatment with glucocorticoids, such as dexamethasone eye drops or dermal application, is rarely recognized. Young infants in particular are at high risk of suffering from iatrogenic Cushing’s syndrome when treated with highly potent topical glucocorticoids.Case presentationWe present a 6-month-old Syrian boy with cushingoid face after dermal clobetasol cream treatment and a 2-year-old Iranian girl with severe growth retardation after application of dexamethasone eye drops. Both families have a migration background and language barriers. In both cases no endogenous cortisol secretion was initially detected in serum and in 24-hour collected urine. After dose reduction of glucocorticoids, severity of symptoms was reversible and serum cortisol was detectable.Discussion and conclusionYoung infants are at high risk of developing Cushing’s syndrome from topically applied highly potent glucocorticoids. Precise recommendations of treatment dosage, duration, and frequency must be given to the parents, and if necessary, with the help of an interpreter. Monitoring of height and weight as well as regular pediatric follow-ups should be scheduled. Physicians should be aware of potential adrenal insufficiency following withdrawal from long-term topical glucocorticoid treatment, and hydrocortisone treatment should be considered.

Ruxolitinib for Treatment of Steroid Refractory Sclerotic Chronic Graft-Versus-Host Disease (cGVHD): Results of a Multicenter Phase II Trial

Background: Sclerotic cGVHD is a highly morbid form of cGVHD, often refractory to standard and secondary therapies and associated with significant decline in patients' quality of life and functioning. We conducted a single-arm phase II multicenter trial to test the hypothesis that ruxolitinib is effective treatment for steroid refractory sclerotic cGVHD (ClinicalTrials.gov ID: NCT03616184). Methods: Eligibility criteria included adults with cGVHD and skin, joint and/or fascia sclerosis, who had received systemic corticosteroids for >12 months and at least one additional line of therapy, or systemic corticosteroids and at least two additional lines of therapy. Subjects received oral ruxolitinib 10 mg twice daily for 6 months, which was subsequently tapered over another month. Treatment could be extended up to 12 months in patients deriving clinical benefit. The primary objective was to determine the proportion of patients with an NIH-defined response in skin or joints at 6 months. A sample size of 47 patients (estimated 10% drop out) had α of 0.044 and a power of 84% to test the null hypothesis response rate of 25% (Clin Cancer Res. 2016; 22: 319-327) compared to an alternative of 45%. Other endpoints included overall response, non-relapse mortality (NRM), treatment failure (administration of additional systemic therapy, malignancy relapse or mortality), glucocorticoid dose reduction, and patient-reported outcomes (PROs) (Lee symptom scale and Scleroderma Health Assessment Questionnaire). Results: 49 patients were consented between November 2018- June 2021; 2 patients were screen failures. Baseline characteristics of 47 patients included a mean age of 58 (range 23-76) years, 40% female, and 91% white. 87% had peripheral blood as a graft source. 66% had matched unrelated donor transplant. 66% had prior acute GVHD. Median time from cGVHD diagnosis to enrollment was about 48 months. All patients had classic cGVHD at enrollment. Severity included mild (2%), moderate (13%) or severe (85%). Patients had received a mean of 3 prior lines of treatment. Patients received a mean of 8.6 cycles of ruxolitinib. 13% had missing data that precluded response assessment; these patients were considered non-responders. Partial responses (PR) in skin or joint (primary endpoint) were seen in 49% (95% CI 34-64%) at 6 months; other responses included stable disease (19%), progression (19%) and missing (13%) (Fig 1). No complete responses were observed in skin or joint. Overall cGVHD partial responses were seen in 47% (95% CI 32-61%); other responses included stable disease (13%), mixed responses/progression (27%) and missing (13%). PR/CR in individual organs (among those with organ involvement after excluding missing data) were as following: eye (12/32, 37%), mouth (9/17, 53%), esophagus (5/9, 55%), upper GI (2/3, 67%), lower GI (2/3, 67%), lung (1/9, 11%), and liver (5/14, 36%). 24% (95% CI 11.8-41.2%) had >50% reduction in glucocorticoid dose from baseline to 6 months. The cumulative incidences of treatment failure and NRM at 6 months were 15.2% (95% CI 6.6- 27.1%) and 2.2% (95% CI 0.2-10.3%). No patients have had relapse of malignancy. 6-month failure free survival was 84.8% (95% CI 70.7-92.4%) (Fig 2). Any grade and grade 3 or higher adverse events occurred in 55% (n=26) and 36% (n=17) of patients. 6 out of 17 grade 3 or higher adverse events were considered possibly or probably related to ruxolitinib. AE occurring in >10% of patients included dry eye, diarrhea, nausea, vomiting, infection, upper respiratory tract infection, weight gain, laboratory and other abnormalities. PRO analyses are ongoing and will be presented. Discussion: The trial met its primary endpoint with half of adults with moderate-severe sclerotic cGVHD achieving partial responses in skin or joint as well as overall cGVHD responses. The use of ruxolitinib was associated with high rates of failure-free survival. In conclusion, the use of ruxolitinib results in high rate of responses in highly morbid sclerotic form of cGVHD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical characteristics and treatment of elderly onset adult-onset Still\u2019s disease

Adult-onset Still’s disease (AOSD)—a systemic inflammatory disease—often occurs at a young age. Recently, elderly onset patient proportion has been increasing; however, data are limited. To evaluate the characteristics of elderly patients with AOSD in a multicenter cohort, we retrospectively analyzed 62 patients with AOSD at five hospitals during April 2008–December 2020. Patients were divided into two groups according to age at disease onset: younger-onset (≤ 64 years) and elderly onset (≥ 65 years). Clinical symptoms, complications, laboratory findings, treatment, and outcomes were compared. Twenty-six (41.9%) patients developed AOSD at age ≥ 65 years. The elderly onset group had a lower frequency of sore throat (53.8% vs. 86.1%), higher frequency of pleuritis (46.2% vs. 16.7%), and higher complication rates of disseminated intravascular coagulation (30.8% vs. 8.3%) and macrophage activation syndrome (19.2% vs. 2.8%) than the younger onset group. Cytomegalovirus infections were frequent in elderly onset patients (38.5% vs. 13.9%) but decreased with early glucocorticoid dose reduction and increased immunosuppressant and tocilizumab use. Elderly AOSD is not uncommon; these patients have different characteristics than younger-onset patients. Devising a way to control disease activity quickly while managing infections may be an important goal in elderly AOSD.

Modified-release hydrocortisone improves androgen excess and facilitates glucocorticoid dose reduction in patients with classic congenital adrenal hyperplasia: non-invasive monitoring in saliva and urine

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Successful discontinuation of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis in real-world settings

Objectives To analyze the proportion of successful biological disease-modifying antirheumatic drugs (bDMARDs) discontinuation and related factors in patients with rheumatoid arthritis (RA) in clinical settings. Methods Among 1775 RA patients who started bDMARDs between 2003 and 2012, 43 patients with DAS28-ESR <3.2 at the time of bDMARD discontinuation were extracted. Patients were divided into two groups (bio-free success: BS and bio-free failure: BF groups) based on bDMARD usage and disease activity 1 year after discontinuation. We evaluated the proportion of bio-free success and assessed factors related to bio-free success. Results Twenty-five patients (58.1%: BS group) maintained discontinuation of bDMARDs and DAS28-ESR <3.2 at 1 year after discontinuation. The median DAS28-ESR at bDMARD initiation was lower in the BS group than in the BF group (3.95 vs 5.04; p = .04). The BS group experienced a larger decrease in average glucocorticoid (GC) dose during bDMARD use than the BF group (−3.0 mg/day vs 0 mg/day; p = .01). Conclusion bDMARDs were discontinued without flare up of RA in 58.1% of patients with RA in clinical settings. A lower DAS28-ESR at initiation and reduction of GC dose before discontinuation of bDMARD were important factors associated with bio-free success.

Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis: A systematic literature review.

We investigated the effectiveness of rituximab (an anti-CD20 monoclonal antibody) in patients with eosinophilic granulomatosis with polyangiitis (EGPA). We performed a systematic literature review from the inception dates until July 20, 2020 for articles reporting rituximab administration to treat EGPA. We identified a total of 171 patients; most of the patients had refractory or relapsing disease, whereas 14 patients were newly diagnosed with EGPA. Rituximab was used for induction therapy in all patients and administered as four infusions of 375mg/m2/week, or two infusions of 1000mg, given 2weeks apart. The observation period was 6-36months after rituximab initiation. The remission rates (defined as a Birmingham Vasculitis Activity Score of 0 along with low dose glucocorticoid) were 36 to 100%. Anti-neutrophil cytoplasmic antibody (ANCA)-positive patients tended to respond better to rituximab than ANCA-negative patients. All studies reported the successful reduction of glucocorticoid dose after rituximab treatment. The median glucocorticoid dose at rituximab initiation was 12.5-60mg/day, which was successfully reduced to 0-8.5mg/day after rituximab treatment. Scheduled rituximab maintenance treatment significantly reduced the relapse rates as compared to rituximab administered on demand. No new safety signal was reported. Rituximab effectively induced and sustained remission and reduced glucocorticoid dose in patients with newly diagnosed or relapsing and refractory EGPA; it also showed potentially greater benefit in ANCA-positive patients than in ANCA-negative patients.

Favorable efficacy of rituximab in ANCA-associated vasculitis patients with excessive B cell differentiation

ObjectivesB cell depletion by rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, peripheral B cell phenotypes and the selection criteria for RTX therapy in AAV remain unclear.MethodsPhenotypic characterization of circulating B cells was performed by 8-color flow cytometric analysis in 54 newly diagnosed AAV patients (20 granulomatosis with polyangiitis and 34 microscopic polyangiitis). Patients were considered eligible to receive intravenous cyclophosphamide pulse (IV-CY) or RTX. All patients also received high-dose glucocorticoids (GC). We assessed circulating B cell phenotypes and evaluated the efficacy after 6 months of treatment.ResultsThere were no significant differences in the rate of clinical improvement, relapses, or serious adverse events between patients receiving RTX and IV-CY. The rate of Birmingham Vasculitis Activity Score (BVAS) improvement at 6 months tended to be higher in the RTX group than in the IV-CY group. The proportion of effector or class-switched memory B cells increased in 24 out of 54 patients (44%). The proportions of peripheral T and B cell phenotypes did not correlate with BVAS at baseline. However, among peripheral B cells, the proportion of class-switched memory B cells negatively correlated with the rate of improvement in BVAS at 6 months after treatment initiation (r = − 0.28, p = 0.04). Patients with excessive B cell differentiation were defined as those in whom the proportion of class-switched memory B cells or IgD−CD27− B cells among all B cells was > 2 SDs higher than the mean in the HCs. The rate of BVAS remission in patients with excessive B cell differentiation was significantly lower than that in patients without. In patients with excessive B cell differentiation, the survival rate, the rate of BVAS-remission, and dose reduction of GC were significantly improved in the RTX group compared to those in the IV-CY group after 6 months of treatment.ConclusionsThe presence of excessive B cell differentiation was associated with treatment resistance. However, in patients with circulating B cell abnormality, RTX was effective and increased survival compared to IV-CY. The results suggest that multi-color flow cytometry may be useful to determine the selection criteria for RTX therapy in AAV patients.

101 Efficacy of tocilizumab use in giant cell arteritis (GCA) and Takayasu arteritis (TA) patients allowing glucocorticoid dose reduction

101 Efficacy of tocilizumab use in giant cell arteritis (GCA) and Takayasu arteritis (TA) patients allowing glucocorticoid dose reduction

Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials

ObjectivesTo evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA).MethodsPatients (2–19 years) entered two phase III studies and continued in the long-term...

Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile Dermatomyositis Shown by Marginal Structural Modeling.

ObjectiveIn patients with severe or refractory juvenile dermatomyositis (DM), second‐line treatments may be required. Cyclophosphamide (CYC) is used to treat some connective tissue diseases, but evidence of its efficacy in juvenile DM is limited. This study was undertaken to describe clinical improvement in juvenile DM patients treated with CYC and model the efficacy of CYC treatment compared to no CYC treatment.MethodsClinical data on skin, global, and muscle disease for patients recruited to the Juvenile DM Cohort and Biomarker Study were analyzed. Clinical improvement following CYC treatment was described using unadjusted analysis. Marginal structural models (MSMs) were used to model treatment efficacy and adjust for confounding by indication.ResultsCompared to the start of CYC treatment, there were reductions at 6, 12, and 24 months in skin disease (P = 1.3 × 10‐10), global disease (P = 2.4 × 10‐8), and muscle disease (P = 8.0 × 10‐10) for 56 patients treated with CYC in unadjusted analysis. Limited evidence suggested a reduction in glucocorticoid dose (P = 0.047) in patients treated with CYC. MSM analysis showed reduced global disease and skin disease in patients who started an ~6‐month course of CYC treatment >12 months ago compared to patients never or not yet treated with CYC. In the treated patients, the modified skin Disease Activity Score for juvenile DM was 1.19 units lower (P = 0.0085) and the physician's global assessment was 0.66 units lower (P = 0.027). Minor adverse events were reported in 3 patients within 1 year of stopping CYC.ConclusionOur findings indicate that CYC is efficacious with no short‐term side effects. Improvements in skin, global, and muscle disease were observed. Further studies are required to evaluate longer‐term side effects.

Real-World Treatment Patterns for Golimumab and Concomitant Medications in Japanese Rheumatoid Arthritis Patients.

The aim of this study was to investigate real-world treatment patterns for use of golimumab and concomitant medications in Japanese patients with rheumatoid arthritis. This study was a post hoc retrospective analysis from post-marketing surveillance data on 2350 Japanese patients with moderate/severe rheumatoid arthritis who received golimumab for 24weeks. The study population was divided based on initiation treatment or dose adjustment patterns with golimumab, methotrexate, or oral glucocorticoids. Logistic regression analysis revealed that the baseline factors associated with administration of golimumab (100mg) were higher body weight, failure of prior biological therapy (bio-failure), no previous methotrexate use, and respiratory disease, while previous methotrexate use and absence of renal impairment or respiratory disease were associated with concomitant methotrexate therapy, and previous glucocorticoid use was associated with concomitant glucocorticoid therapy. The following associations were identified with regard to dose adjustment during treatment: bio-failure, no previous methotrexate use, previous csDMARDs use, presence of respiratory disease, allergy history, and higher CRP for golimumab dose escalation; shorter disease duration, previous GC, and no previous methotrexate use for methotrexate dose escalation; no prior biological therapy and renal impairment for methotrexate dose reduction; no previous GC use for glucocorticoid dose escalation; and absence of Steinbrocker's stage II/III/IV, absence of Steinbrocker's class II, no bio-failure, and no previous csDMARDs use for glucocorticoid dose reduction. This study revealed that various baseline factors were associated with initiation of treatment and dose adjustment of golimumab, methotrexate, or oral glucocorticoids, reflecting both the treatment strategies of physicians for improving RA symptoms and/or reducing adverse events. Janssen Pharmaceutical K.K. and MitsubishiTanabe Pharma Corporation.

Decrease in salivary cortisol levels after glucocorticoid dose reduction in patients with adrenal insufficiency: A prospective proof-of-concept study.

Patients with adrenal insufficiency (AI) require lifelong glucocorticoid (GC) replacement therapy. Cortisol measurement in saliva is increasingly being used: we assessed salivary cortisol rhythm in outpatients with AI, to provide new insights regarding the management of GC treatment. Nineteen AI outpatients collected six saliva samples from awakening (Fa , before taking the morning GC therapy), during the day (F1.5h , F6h before the afternoon GC dose, F8.5h , F12h ) until bedtime (Fb ). We measured daily cortisol exposure by calculating the area under the curve (AUCFa→Fb ). Saliva samples were collected at baseline and one year after GG dose reduction (by at least 5mg of hydrocortisone). Hydrocortisone equivalents decreased from median 25mg/d (baseline, interquartile range IQR 20-27.5) to 15mg/d (IQR 15-20, P<.01). As expected, we observed a reduction in both daily cortisol exposure (AUCFa→Fb 23982nmol·h/L, IQR 12635-45369, to 14689nmol·h/L, IQR 7168-25378, P<.001) and salivary cortisol levels at F6h (24.8nmol/L, IQR 20.1-35.7, to 21nmol/L, IQR 8.7-29.2, P<.05) and Fb (8.7nmol/L, IQR 3.4-20.2, to 3.7nmol/L, IQR 3.0-5.8, P<.05). None of the patients developed signs or symptoms consistent with AI after GC reduction. Median diastolic blood pressure (DPB) values fell from baseline to the end of follow-up (87.5mm Hg, IQR 80-90, to 80mm Hg, IQR 80-85, P<.05). The AUCFa→Fb of patients at baseline was above the reference value (90th percentile of controls) in 12 patients (60%); after the dosage reduction, 30% of patients normalized their daily cortisol exposure (AUCFa→Fb ). The reduction in GC treatment in patients with AI resulted in better control of daily cortisol rhythm, measured with salivary cortisol, and in an improvement of DPB. Further studies are needed to ascertain if salivary cortisol could be used as a biomarker to manage GC replacement therapy.

Efficacy and safety of tacrolimus for myasthenia gravis: a systematic review and meta-analysis.

To evaluate the efficacy and safety of tacrolimus in patients with myasthenia gravis (MG), a systematic review and meta-analysis was performed. We searched PubMed and Embase for randomized controlled trials and clinical controlled trials in English language. Demographic and clinical characteristics of the MG patients were extracted. Differences in the current glucocorticoids (GC) dose in each included study were the primary outcome measure. The adverse events reported in each included study were used as safety evaluation. There were 5 trials included involving 683 patients. In this systematic review, we identified treatment with tacrolimus did not exhibit a statistically significant difference in the GC dose reduction at 6months and 12months compared with placebo. The standard mean differences in the GC dose reduction were -1.95 [(-4.20 to 0.30); p=0.09] at 6months and -1.72 [(-4.21 to 0.77); p=0.18] at 12months. But GC dose reduction from baseline in the tacrolimus group exceeded that in the controlled group. The weighted mean differences were -1.34 [(-2.46 to 0.23); p=0.02] in the quantitative myasthenia gravis score and -1.10 [(-1.84 to -0.36); p=0.004] in the myasthenia gravis activities of daily living score at 6months. Adverse events were recorded in 80 of 347 patients (23%) treated with tacrolimus and most of them were mild. This meta-analysis proves that tacrolimus therapy is beneficial to improve clinical symptoms in MG patients. Tacrolimus may be a worthy therapy to relieve MG symptoms.