Discontinuation Of Glucocorticoids Research Articles

Glucocorticoid Exposure and Fracture Risk in a Cohort of US Patients With Selected Conditions.

The purpose of this work was to evaluate systemic glucocorticoid exposure and fracture among patients with newly-diagnosed inflammatory and immune-modulated conditions. Using administrative data, inception cohorts of rheumatoid arthritis (RA), asthma/chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), multiple sclerosis (MS), lupus, and sarcoidosis patients age 18 to 64 years with benefits coverage ≥12 months before diagnosis (January 1, 2005 to December 31, 2012) were followed to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IRs) per 1000 person-years were stratified by prednisone equivalent doses. Cox's proportional hazards models assessed risk by daily and cumulative dose, and by time since discontinuation, adjusted for baseline characteristics. Most patients (72% of 403,337) had glucocorticoid exposure; 52% were under age 50. IR (95% confidence interval [CI]) of any osteoporotic fracture was elevated at doses <5 mg/day (IR 9.33; 95% CI, 7.29 to 11.77) versus 0 mg/day (IR 4.87 (95% CI, 4.72 to 5.02). Fracture rates were elevated at doses <5 mg/day in patients <50 years and those ≥50 years. In both age groups, fracture risk increased with increasing cumulative exposure, being approximately 2.5-fold higher at cumulative dose ≥5400 mg compared to <675 mg. At ≥5400 mg, IR values were 5.69 (95% CI, 4.32 to 7.35) in patients <50 years and 17.10 (95% CI, 14.97 to 19.46) in older patients. Fracture risk decreased significantly within months following glucocorticoid discontinuation. In patients with a variety of inflammatory conditions, fracture risk increased at doses as low as <5 mg/day. Risk increased with increasing cumulative exposure and decreased soon following glucocorticoid discontinuation. Trends were similar between patients older and younger than 50 years. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

An Exploratory Reanalysis of the Randomized Trial on Efficacy of Corticosteroids as Rescue Therapy for the Late Phase of Acute Respiratory Distress Syndrome.

In the Acute Respiratory Distress Syndrome Network randomized controlled trial, methylprednisolone treatment was associated with increased return to mechanical ventilation with partial loss of early improvements. We hypothesize a causal relationship between protocol-driven rapid discontinuation of methylprednisolone post extubation and return to mechanical ventilation. To explore this possibility, we investigated the timing that events occurred in each treatment arm during active treatment intervention (efficacy) and after stopping therapy. Retrospective intention-to-treat analysis of multicenter randomized controlled trial. Patients were randomized to methylprednisolone (2 mg/kg/d) or placebo (89 vs 91). The target sample size was reduced post hoc and provided 80% power for an optimistic 50% mortality reduction. Findings are reported as methylprednisolone versus placebo. By day 28, fewer patients died before achieving extubation (15.7% vs 25.3% and risk ratio, 0.62; 95% CI, 0.34-1.13), more achieved successful extubation (71.9% vs 49.5% and risk ratio, 1.45; CI, 1.14-1.85), time to successful extubation was shorter (hazard ratio, 2.05; CI, 1.42-2.96), and more were discharged alive from the ICU (65.2% vs 48.3%; risk ratio, 1.35; CI, 1.04-1.75). After treatment discontinuation, more methylprednisolone-treated patients returned to mechanical ventilation (26.6% vs 6.7%; risk ratio, 3.98; CI, 1.24-12.79)-consistent with reconstituted systemic inflammation in the presence of adrenal suppression. Participants returning to mechanical ventilation without reinstitution of methylprednisolone had increased risk of ventilator dependence and mortality. Despite loss of early benefits, methylprednisolone was associated with sizable and significant improvements in all secondary outcomes and reduction in serious complications (shock and severe infections). During active intervention, methylprednisolone was safe and effective in achieving disease resolution. Our findings support rapid glucocorticoid discontinuation post extubation as likely cause of disease relapse. Gradual tapering might be necessary to preserve the significant improvements achieved during methylprednisolone administration.

Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis.

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the effect of concomitant methotrexate (MTX) or glucocorticoid (GC) use on tofacitinib clinical efficacy. Data were pooled from two open-label, long-term extension studies of tofacitinib 5 or 10mg twice daily in patients with RA. Response according to Clinical Disease Activity Index (CDAI) was assessed separately in patients who discontinued (no MTX/GC use within 30days prior to year-3 visit; assessment at month 3/year 3) or initiated (on/before year 3; assessment at initiation and year 3) MTX/GC. By year 3, among patients receiving background MTX at baseline, 186/1608 (11.6%) discontinued MTX, and 319/1434 (22.2%) patients receiving GC at baseline discontinued GC. Overall, 70.4/69.1% of patients who discontinued/continued MTX and 72.7/65.9% who discontinued/continued GC achieved CDAI remission or low disease activity (LDA) at year 3. Month 3 remission/LDA rates were maintained at year 3 in the majority of patients, irrespective of MTX/GC discontinuation/continuation. By year 3, 6.2% of patients receiving tofacitinib without MTX at baseline had initiated concomitant MTX, and 25.1% receiving tofacitinib without GC initiated GC; 69.0% and 45.4% initiating MTX or GC, respectively, had a CDAI-defined incomplete response prior to initiation. RA signs/symptoms improved following MTX initiation; only modest improvement was observed with GC initiation. Patients achieving remission/LDA with tofacitinib may discontinue MTX or GC and maintain treatment response. Patients with an incomplete response may benefit from adding concomitant MTX. Pfizer Inc. Study A3921024 [NCT00413699] and StudyA3921041 [NCT00661661].

Large-vessel involvement and aortic dilation in giant-cell arteritis. A multicenter study of 549 patients

Large-vessel involvement (LVI) can occur in giant-cell arteritis (GCA) and may represent a distinct disease subgroup with a higher risk for aortic dilation. This study aimed to better characterize the presentation and evolution of LVI in patients with GCA. A retrospective multicenter study enrolled 248 GCA patients with LVI and 301 GCA patients without LVI on imaging. Factors associated with aortic dilation were identified in a multivariable model. The patients with LVI were younger (p<0.0001), more likely to be women (p=0.01), and showed fewer cephalic symptoms (p<0.0001) and polymyalgia rheumatica (p=0.001) but more extracranial vascular symptoms (p=0.05) than the patients without LVI. Glucocorticoids (GC) management did not differ between the two groups, but the GC discontinuation rate was lower in the patients with LVI (p=0.0003). Repeated aortic imaging procedures were performed at 19months [range: 5-162months] and 17months [range: 6-168months] after diagnosis in 154 patients with LVI and 123 patients without LVI, respectively, of whom 21% and 7%, respectively, presented new aortic dilations (p=0.0008). In the patients with LVI, aortic dilation occurred on an aorta segment shown to be inflammatory on previous imaging in 94% of patients. In the multivariate analysis, LVI was the strongest predictor of aortic dilation (hazard ratio: 3.16 [range: 1.34-7.48], p=0.009). LVI represents a distinct disease pattern of GCA with an increased risk of aortic dilation. Control of the aortic morphology during follow-up is required.

Frequency and Duration of Adrenal Suppression Following Glucocorticoid Therapy in Children With Rheumatic Diseases.

Adrenal suppression (AS), a glucocorticoid (GC) side effect with potentially significant morbidity, is poorly understood. The purpose of our study was to determine frequency, duration, and predictors of AS following a gradual taper of GC in children with rheumatic conditions. A prospective, observational cohort study was conducted. All patients ages ≤16 years ready to discontinue GC after >4 weeks of therapy were included. Morning cortisol was tested 4 weeks after GC taper to physiologic doses and then repeatedly until normalization. GCs were subsequently discontinued and a low-dose adrenocorticotropic hormone stimulation test was performed. The study was completed by 31 of 39 patients. The median age was 12.9 years and median duration of GC therapy was 39.6 weeks. Seventeen patients (54.8%) had AS. Of the patients with AS, 50% showed recovery by 7 months. Two patients had persistent AS at 12 months and 1 patient at 2 years. A higher maximum GC dose was a significant predictor for the development of AS. More than 50% of our patients had AS after GC discontinuation, despite a gradual taper of GC. Stress steroids should be considered in children treated with long-term GC, even after steroid discontinuation, to prevent possible adrenal crisis.

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.

Adrenal suppression in children treated with swallowed fluticasone and oral viscous budesonide for eosinophilic esophagitis.

BackgroundAdrenal suppression (AS), a glucocorticoid (GC) side effect associated with significant morbidity, is well described related to inhaled corticosteroid therapy for asthma. Swallowed topical glucocorticoid therapy is the main pharmacotherapy treatment for eosinophilic esophagitis (EoE) and therefore children with EoE are potentially at increased risk of AS.MethodsIn this prospective cohort study, we included children and youth <18 years diagnosed with EoE and treated with swallowed fluticasone or oral viscous budesonide for more than 1 month. First morning cortisol and low dose adrenocorticotropic hormone stimulation test (LDST) were performed 2 weeks following GC discontinuation. AS was defined as an abnormal LDST result (cortisol peak <500 nmol/L). We determined the prevalence and duration of AS related to swallowed topical GC therapy in EoE by LDST, as well as the diagnostic accuracy of first morning cortisol compared to LDST.ResultsOf 29 participants enrolled, 26 (89.7 %) received oral viscous budesonide and 3 (10.3 %) received swallowed fluticasone. Nineteen (65.5 %) participants had AS. Median duration of AS was 43 weeks. Five (17.2 %) participants had persistent AS at 12 months. There were no identifiable risk factors for the development of AS. First morning cortisol was highly specific but had poor sensitivity for detection of AS.ConclusionsThe majority of children with EoE had AS after discontinuation of swallowed topical GC therapy. Stress steroids should be considered in children treated with swallowed topical GC therapy for EoE, even after GC discontinuation, to prevent possible adrenal crisis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13223-016-0154-9) contains supplementary material, which is available to authorized users.

Effectiveness and safety of tocilizumab in achieving clinical and functional remission, and sustaining efficacy in biologics-naive patients with rheumatoid arthritis: The FIRST Bio study

Objective: To evaluate effectiveness and safety of tocilizumab (TCZ) in biologic-naive Japanese patients with rheumatoid arthritis (RA) in real-world settings, and to analyze the relationship between disease duration and clinical outcomes.Methods: The FIRST Bio study was a postmarketing surveillance study of intravenous TCZ in biologics-naive patients who had a prior inadequate response or were intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Effectiveness, safety, and concomitant csDMARD administration were assessed.Results: Of the 839 patients analyzed, 72.3% completed 52 weeks of treatment. The Clinical Disease Activity Index (CDAI) remission rate at week 52 was 36.8%. Contributing factors for CDAI remission were younger age, early disease stage, and no comorbidities. Health Assessment Questionnaire Disability Index ≤0.5 was achieved in 65.1% of patients, and was significantly associated with disease duration. Discontinuation of concomitant methotrexate (MTX) and glucocorticoids (GCs) was possible in 19.3% and 34.1% of patients, respectively, without decreasing remission rate. The incidence (events/100 patient-years) of serious adverse events was 18.09, the most common being infection.Conclusion: These data validate the importance of TCZ treatment in the early stages of RA in biologic-naive patients to achieve increased effectiveness. The safety profile of TCZ was reconfirmed. Furthermore, TCZ therapy may allow discontinuation of concomitant MTX and GCs without affecting remission.

Outcome of a glucocorticoid discontinuation regimen in patients with inactive systemic sclerosis.

Glucocorticoids (GC) are widely used to treat systemic sclerosis (SSc). The lack of efficacy data and patient/physician concerns may prompt therapy discontinuation. The aim of this study is to identify factors hampering GC discontinuation in patients with stable disease on oral GC for longer than 12months. Consecutive patients fulfilling the 2013 ACR/EULAR criteria for SSc and with stable disease were prescribed a slow tapering GC regimen to achieve discontinuation. At study entry and 6months later (T6), patients were assessed for disease activity and severity. Moreover, the Short-Form-36; the Health Assessment Questionnaire Disability Index (HAQ-DI); and visual analog scales for fatigue, pain, and general health were completed. Reasons for stopping the discontinuation regimen were recorded. Forty-eight patients (46 females, 9 diffuse SSc), with a mean ± SD age of 56±14years and a median disease duration of 10years (range 2-22), were enrolled. The median daily GC dose was 5mg (range 5-10; all patients treated with prednisone). At T6, 33 (68.7%) patients had discontinued GC. The remaining 15 patients could not discontinue GC because of arthralgia in eight, arthritis in two, puffy fingers in two, increased creatine-kinase in two, and bursitis in one patient. At multiple logistic analysis, a higher baseline HAQ-DI was the only independent factor associated with GC need (OR 2.98, 95% CI 1.20-7.41; p = 0.01). About one third of SSc patients did not achieve a GC-free regimen. Disability as assessed by HAQ-DI was the leading factor hindering GC discontinuation. A low HAQ-DI score can identify candidates for GC discontinuation.

Ipilimumab-Induced Hypophysitis May Not Affect All Pituitary Cell Lines: A Case Report

Hypophysitis, a rare autoimmune condition, has now emerged as an adverse effect of ipilimumab (anti-cytotoxic T lymphocyte antigen 4 (CTLA4) mAb) therapy. The occurrence of ipilimumab-induced hypophysitis (IH) in studies has varied from 0% to 17%. This condition, because of secondary adrenal insufficiency, may be life-threatening if not recognized and managed promptly. Here we present a case of hypophysitis in the setting of ipilimumab therapy for malignant melanoma. The patient initially presented to his oncologist with a headache, diplopia, fatigue, nausea, hot flashes, anorexia and decreased libido shortly following the third cycle of ipilimumab. He was found to have pituitary enlargement with heterogeneous enhancement on magnetic resonance imaging (MRI). The initial diagnosis was based on clinical features, MRI findings and laboratory evidence of central hypogonadism and adrenal insufficiency. Other hormone levels were not tested that time and were only tested 5 months later when the patient did not tolerate the discontinuation of glucocorticoids. He continued to require glucocorticoid and testosterone replacement 14 months after the diagnosis. This case demonstrates IH causing anterior hypopituitarism leading to central hypoadrenalism, central hypogonadism, reduced prolactin and possibly central hypothyroidism but preserved somatotroph function. Pituitary antibodies may be a possible method of detection of IH in addition to MRI and hormonal investigations. There is insufficient evidence to support the need for discontinuing ipilimumab or the superiority of initial high dose versus physiologic steroid and hormone replacement in the management of IH. Hypopituitarism due to IH may persist for several months or longer after ipilimumab is discontinued. This underlies the importance of continuous supplementation with all the hormones that are deficient as a consequence of hypopituitarism caused by IH. J Endocrinol Metab. 2015;5(5):299-303 doi: http://dx.doi.org/10.14740/jem287w

Outcome and toxicity assessment of feline small cell lymphoma: 56 cases (2000-2010).

Feline small cell lymphoma is associated with greater response to treatment and survival when compared to large cell lymphoma. Treatment‐associated toxicity, response to rescue chemotherapy and prognostic factors are largely unknown. This retrospective study was performed to identify treatment‐associated toxicity, response to rescue chemotherapy and treatment outcome for cats diagnosed with small cell lymphoma of various anatomic locations. Medical records from 56 cats were evaluated. All cats were treated with glucocorticoid and chlorambucil with discontinuation of treatment recommended at 1 year if complete clinical response was documented. Chemotherapy toxicity was uncommon (33.9%) and generally mild. Grade III or IV hepatotoxicity was documented in 10.7% of patients. Overall response rate was 85.7% with glucocorticoid and chlorambucil. Median progression‐free survival was 1078 days. Overall response rate for rescue chemotherapy was 59%. Reintroduction of prednisone and chlorambucil was associated with significantly longer survival than prednisone and lomustine (>1500 vs. 492 days, P = 0.01). Median overall survival times for cats with lymphoma of the gastrointestinal tract was not significantly different from those with extra‐intestinal disease locations (1148 vs. 1375 days, P = 0.23). Median overall survival was 1317 days. Toxicity, other than hepatotoxicity was mild. Rescue chemotherapy with re‐introduction of glucocorticoids and chlorambucil was most successful. Discontinuation of glucocorticoid and chlorambucil with subsequent reintroduction as rescue chemotherapy appears to be just as effective as continued administration in cats.

Effectiveness and Safety of Anakinra for Management of Refractory Pericarditis

Recurrent pericarditis is a debilitating condition that can be recalcitrant to conventional therapy with nonsteroidal anti-inflammatory agents, colchicine, and glucocorticoids. The aim of this study was to evaluate the therapeutic role of the recombinant interleukin-1 receptor antagonist anakinra in a series of adult patients with recurrent pericarditis refractory to conventional therapy. We retrospectively reviewed the medical records of 13 consecutive patients with treatment-refractory recurrent pericarditis who received anakinra for management of their disease. None of the patients had an identified systemic inflammatory rheumatic disease. The primary end points were symptom resolution and glucocorticoid discontinuation. Thirteen patients (10 women) treated with anakinra were followed for a median (range) of 16.8 months (1.3 to 24). All patients had chest pain. Total duration of symptoms before initiation of anakinra was 3 years (1.1 to 6.0). Pericardial thickening was detected by echocardiography in 9 patients (69%). All 13 patients (100%) experienced at least a partial and, most, a complete resolution of symptoms. Response to therapy was rapid, within 2 to 5days. At last follow-up, 11 patients (84%) had successfully discontinued concomitant nonsteroidal anti-inflammatory agent, colchicine, and glucocorticoid therapy; 11 patients remained on anakinra at the end of the follow-up period. The only side effect was transient injection site reaction in 4 patients (31%). In conclusion, anakinra may be an effective alternative agent for the management of glucocorticoid-dependent recurrent pericarditis. Side effects were minor. A formal clinical trial to evaluate the usefulness of this agent should be considered.

Bortezomib-induced acute interstitial nephritis

Acute interstitial nephritis (AIN) is one of the important causes of acute kidney injury (AKI) resulting from inflammatory tubulointerstitial injury induced by medications, infections and systemic diseases. Bortezomib has been increasingly used especially in renal related indications such as multiple myeloma and monoclonal gammopathy of renal significance. Severe allergic reactions from bortezomib treatment including AIN have not been described in the literature. We report a 47-year-old white man who developed biopsy-proven allergic AIN after treatment with bortezomib for his C3 glomerulonephritis. The patient's kidney function improved after treatment with glucocorticoid therapy and discontinuation of bortezomib, but worsened with recurrent AKI episode after re-initiation of bortezomib. His renal function improved after glucocorticoid therapy and discontinuation of bortezomib. To our knowledge, this is the first report of a biopsy-proven AIN from bortezomib.

Adrenal Insufficiency in Corticosteroids Use: Systematic Review and Meta-Analysis.

We aimed to estimate pooled percentages of patients with adrenal insufficiency after treatment with corticosteroids for various conditions in a meta-analysis. Secondly, we aimed to stratify the results by route of administration, disease, treatment dose, and duration. We searched seven electronic databases (PubMed, MEDLINE, EMBASE, COCHRANE, CENTRAL, Web of Science, and CINAHL/Academic Search Premier) in February 2014 to identify potentially relevant studies. Original articles testing adult corticosteroid users for adrenal insufficiency were eligible. We included 74 articles with a total of 3753 participants. Stratified by administration form, percentages of patients with adrenal insufficiency ranged from 4.2% for nasal administration (95% confidence interval [CI], 0.5-28.9) to 52.2% for intra-articular administration (95% CI, 40.5-63.6). Stratified by disease, percentages ranged from 6.8% for asthma with inhalation corticosteroids only (95% CI, 3.8-12.0) to 60.0% for hematological malignancies (95% CI, 38.0-78.6). The risk also varied according to dose from 2.4% (95% CI, 0.6-9.3) (low dose) to 21.5% (95% CI, 12.0-35.5) (high dose), and according to treatment duration from 1.4% (95% CI, 0.3-7.4) (<28 d) to 27.4% (95% CI, 17.7-39.8) (>1 year) in asthma patients. 1) Adrenal insufficiency after discontinuation of glucocorticoid occurs frequently; 2) there is no administration form, dosing, treatment duration, or underlying disease for which adrenal insufficiency can be excluded with certainty, although higher dose and longer use give the highest risk; 3) the threshold to test corticosteroid users for adrenal insufficiency should be low in clinical practice, especially for those patients with nonspecific symptoms after cessation.

Cytokine storm after cessation of tocilizumab in a patient with refractory Takayasu arteritis

Takayasu arteritis (TAK) is an autoimmune large vessel vasculitis of unknown pathogenesis mainly affecting aorta and its major branches [ [1] Isobe M. Takayasu arteritis revisited: current diagnosis and treatment. Int. J. Cardiol. 2013; 168: 3-10 Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar ]. Glucocorticoids (GCs) are the principal therapy for the treatment of TAK [ [2] Mukhtyar C. Guillevin L. Cid M.C. et al. EULAR recommendations for the management of large vessel vasculitis. Ann. Rheum. Dis. 2009; 68: 318-323 Crossref PubMed Scopus (482) Google Scholar ]. Although GCs suppress the clinical symptoms and signs of inflammation when administered in moderate to high doses, a sizable number of patients relapse upon tapering of the GC dose or discontinuation [ [3] Maksimowicz-McKinnon K. Clark T.M. Hoffman G.S. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 2007; 56: 1000-1009 Crossref PubMed Scopus (372) Google Scholar ]. Recent studies have shown that interleukin-6 (IL-6) blockade with the anti-human IL-6 receptor (IL-6R) humanized monoclonal antibody, tocilizumab (TCZ), might be effective for treating the refractory patients with TAK [ 4 Nishimoto N. Nakahara H. Yoshio-Hoshino N. Mima T. Successful treatment of a patient with Takayasu arteritis using a humanized anti-interleukin-6 receptor antibody. Arthritis Rheum. 2008; 58: 1197-1200 Crossref PubMed Scopus (170) Google Scholar , 5 Salvarani C. Magnani L. Catanoso M. et al. Tocilizumab: a novel therapy for patients with large-vessel vasculitis. Rheumatology. 2012; 51: 151-156 Crossref PubMed Scopus (188) Google Scholar , 6 Seitz M. Reichenbach S. Bonel H.M. Adler S. Wermelinger F. Villiger P.M. Rapid induction of remission in large vessel vasculitis by IL-6 blockade. Swiss Med. Wkly. 2011; 141 PubMed Google Scholar , 7 Unizony S. Arias-Urdaneta L. Miloslavsky E. Arvikar S. Khosroshahi A. Keroack B. Stone J.R. Stone J.H. Tocilizumab for the treatmen of large-vessel vasculitis (giant cell areritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res. (Hoboken). 2012; 64: 1720-1729 Crossref PubMed Scopus (236) Google Scholar , 8 Nakaoka Y. Higuchi K. Arita Y. et al. Tocilizumab for the treatment of patients with refractory Takayasu arteritis. Int. Heart J. 2013; 54: 405-411 Crossref PubMed Scopus (56) Google Scholar ]. Since continuous therapy with TCZ strains medical finances due to its expensive cost, we need to develop safe methods for terminating TCZ therapy after induction of remission. In addition, it is unclear whether discontinuation of TCZ might cause a disease flare-up in a TAK patient in remission. Here, we present a TAK patient who showed a recurrence of TAK after cessation of TCZ with elevation of various inflammatory cytokines, so-called “cytokine storm”. Retreatment with TCZ and a subsequent administration of methotrexate (MTX) along with of the dosage increment in GCs were successful for maintaining remission.

Ipilimumab-Induced Hypophysitis May Not Affect All Pituitary Cell Lines: A Case Report

Hypophysitis, a rare autoimmune condition, has now emerged as an adverse effect of ipilimumab (anti-cytotoxic T lymphocyte antigen 4 (CTLA4) mAb) therapy. The occurrence of ipilimumab-induced hypophysitis (IH) in studies has varied from 0% to 17%. This condition, because of secondary adrenal insufficiency, may be life-threatening if not recognized and managed promptly. Here we present a case of hypophysitis in the setting of ipilimumab therapy for malignant melanoma. The patient initially presented to his oncologist with a headache, diplopia, fatigue, nausea, hot flashes, anorexia and decreased libido shortly following the third cycle of ipilimumab. He was found to have pituitary enlargement with heterogeneous enhancement on magnetic resonance imaging (MRI). The initial diagnosis was based on clinical features, MRI findings and laboratory evidence of central hypogonadism and adrenal insufficiency. Other hormone levels were not tested that time and were only tested 5 months later when the patient did not tolerate the discontinuation of glucocorticoids. He continued to require glucocorticoid and testosterone replacement 14 months after the diagnosis. This case demonstrates IH causing anterior hypopituitarism leading to central hypoadrenalism, central hypogonadism, reduced prolactin and possibly central hypothyroidism but preserved somatotroph function. Pituitary antibodies may be a possible method of detection of IH in addition to MRI and hormonal investigations. There is insufficient evidence to support the need for discontinuing ipilimumab or the superiority of initial high dose versus physiologic steroid and hormone replacement in the management of IH. Hypopituitarism due to IH may persist for several months or longer after ipilimumab is discontinued. This underlies the importance of continuous supplementation with all the hormones that are deficient as a consequence of hypopituitarism caused by IH. J Endocrinol Metab. 2015;5(5):299-303 doi: http://dx.doi.org/10.14740/jem287w

Bone health in children and adolescents with steroid-sensitive nephrotic syndrome assessed by DXA and QUS.

The management of steroid-sensitive nephrotic syndrome (SSNS) requires treatment with high-dose glucocorticoids (GCs), but GC usage causes the most frequent form of drug-induced osteoporosis. The aim of our study was to evaluate the impact of GCs on bone mineralization in patients with SSNS using two diagnostic tools, dual-energy X-ray densitometry (DXA) and quantitative ultrasound (QUS), and to compare the diagnostic efficacy of these two imaging tools. A total of 30 children with SSNS (age 5.20 ± 2.20years) were evaluated at the start (T0) and after 1 (T1), 2.44 ± 0.75 (T2, 18 patients) and 5.96 ± 2.33years (T4, 12 patients) of GC treatment. Patients who stopped at T2 were also evaluated at the 1-year timepoint after ceasing GC treatment (T3). Of the patients assessed at T2, 11 had bone mineralization at the lower limit of normal versus those at T0 and T1, with bone mineralization rescue at the 1-year timepoint after GC discontinuation. At T4, 6/12 patients had densitometric parameters at the lower limit of normal values, and 3/12 patients showed reduced bone mineralization. The parameters derived from measurements of DXA and QUS were significantly related to each timepoint. Patients with SSNS receiving GC therapy undergo bone status alteration related to the dosage and duration of the therapy. In terms of diagnostic efficacy, DXA and QUS were comparable, indicating that QUS is a reliable tool to evaluate bone health in children with SSNS.

AB0596 Glucocorticoid-Resistant Polymyalgia Rheumatica: Clinical Characterization and TOCILIZUMAB Therapy

BackgroundTreatment with glucocorticoid (GC) is the preferred therapy for polymyalgia rheumatica (PMR), but half of the PMR patients experience a flare-up(s) of disease activity upon GC tapering or discontinuation. In...

Rituximab for minimal change disease in adults: long-term follow-up

Minimal change nephropathy or disease (MCD) accounts for 10-15% of cases of the nephrotic syndrome in adults with frequent relapses occurring in up to 25% of cases. The drug of choice is glucocorticoids (GCs), but GC-dependence is seen in 25-30%. Treatment with rituximab has been found to be effective in relapsing and GC-dependent cases, but little data are available regarding long-term outcome in adults. We present nine female and seven male patients, ranging from 19 to 73 years of age with multirelapsing, GC-dependent or GC-resistant disease with a kidney biopsy consistent with MCD. Twelve patients were steroid-dependent with a lowest daily GC dose between 5 and 20 mg/day. Rituximab with a total dose 1000-2800 mg divided in two to four doses was given together with GC achieving B-cell depletion before the second dose. No major side-effects occurred. Thirteen of the patients responded with complete remission enabling discontinuation or tapering of GC significantly below levels, where relapses had occurred in the past (P < 0.001). Two patients reached partial remission and one had no response to therapy. Follow-up was 12-70 months (median 44). Eight patients have remained in remission, whereas relapses occurred in seven patients after 9-28 months with repeated rituximab treatment in four of these. Our study reinforces the role of rituximab as a GC-sparing agent in the challenging GC-dependent and multirelapsing MCD patients. In this emerging therapeutic field randomized studies with extended follow-up will add important information regarding optimal treatment, relapse and safety.

SAT0552 Management of Rheumatoid Arthritis in Remission in Current Practice : the 3P Study

BackgroundThe goal of current rheumatoid arthritis management is to achieve remission or low disease activity1. However few studies have been performed on the management of patients in sustained remission, especially...