Weeks Of Glucocorticoid Treatment Research Articles

Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial

Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5-15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4-6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012. Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35-0·73) with tapered prednisone and -0·08 (-0·27 to 0·12) with continued prednisone (difference 0·61 [0·35-0·88]; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71-0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency. In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. F Hoffmann-La Roche.

Tapering glucocorticoids in rheumatoid arthritis

Glucocorticoids are a cornerstone of care for patients with rheumatoid arthritis. Since the 1950s, glucocorticoids have been used to reduce inflammation and symptoms of arthritis, improve physical function, and reduce disability. These drugs are widely available, inexpensive, and typically combined with disease-modifying antirheumatic drugs to induce remission in rheumatoid arthritis. However, the administration of glucocorticoids is not without risk. Long-term use of glucocorticoids is associated with increased mortality, 1 Chester Wasko M Dasgupta A Ilse Sears G Fries JF Ward MM Prednisone use and risk of mortality in patients with rheumatoid arthritis: moderation by use of disease-modifying antirheumatic drugs. Arthritis Care Res. 2016; 68: 706-710 Crossref PubMed Scopus (32) Google Scholar cardiovascular events, 2 Roubille C Richer V Starnino T et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriaznn. Rheum Dis. 2015; 74: 480-489 Crossref PubMed Scopus (512) Google Scholar and bone fractures. 3 Tong JJ Xu SQ Zong HX Pan MJ Teng YZ Xu JH Prevalence and risk factors associated with vertebral osteoporotic fractures in patients with rheumatoid arthritis. Clin Rheumatol. 2020; 39: 357-364 Crossref PubMed Scopus (20) Google Scholar For this reason, rheumatoid arthritis management guidelines advocate using low-dose glucocorticoids (≤10 mg daily of a prednisone equivalent) during the initiation of a new disease-modifying antirheumatic drug and for a relatively short duration (<3 months) when treating a flare. 4 Singh JA Saag KG Bridges SL et al. 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016; 68: 1-26 Crossref PubMed Scopus (2102) Google Scholar , 5 Smolen JS Landewé R Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017; 76: 960-977 Crossref PubMed Scopus (1714) Google Scholar Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trialIn patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. Full-Text PDF

Two cases of immunoglobulin G4 (IgG4)-related hypophysitis diagnosed without pituitary biopsy.

Background:Immunoglobulin G4-related hypophysitis (IgG4-RH) is a rare disease, diagnosis of which typically depends on histopathology following an invasive pituitary biopsy, possibly leading to permanent hypopituitarism. Herein, we report two cases of IgG4-RH with favorable responses to glucocorticoids. One of them was multiple organs involved and treated with glucocorticoids and methotrexate.Methods:We retrospectively review clinical features, radiological images, and treatment of two cases with IgG4-RH. In addition, literature on IgG4-RH was comprehensively reviewed and a new therapeutic strategy for IgG4-RH was provided.Results:A 45-year-old man presented with diabetes insipidus for 6 months. Pituitary magnetic resonance imaging (MRI) indicated thickening of pituitary stalk. His serum IgG4 was 13,500 mg/l and hormonal evaluation revealed isolated growth hormone deficiency. Pituitary biopsy was denied by the patient due to fears of permanent pituitary damage. Treatment with prednisone and methotrexate (MTX) for 1 week led to improvement in sellar images and reduction in IgG4 level. His IGF1 (insulin-like growth factor-1) recovered after a 4-month treatment. The second case is a 43-year-old woman presenting with diabetes insipidus and amenorrhea for 20 months. Her pituitary MRI was similar to the patient above. Her serum IgG4 level was 5980 mg/l and hormonal measurement confirmed isolated hypogonadotropic hypogonadism. After 2 weeks of prednisone, the sellar images improved. After 3 months of treatment, her pituitary MRI was normal, IgG4 level had decreased to near normal range, and menstruation resumed. Literature review found additional patients with IgG4-RH, who were treated successfully without invasive pituitary biopsy in a manner similar to our cases. Therefore, we discuss the necessity of invasive pituitary biopsy for IgG4-RH.Conclusion:For suspected IgG4-RH with pituitary hormone deficiency, biopsy-induced hypopituitarism may be avoided by using diagnostic glucocorticoid treatment. Impaired pituitary hormone secretion may be recovered in response to steroid therapy. Improved pituitary MRI after 1–2 weeks of glucocorticoid treatment may provide diagnostic evidence of IgG4-RH.

Diabetes mellitus and hyperglycemic complications in bullous pemphigoid

Diabetes mellitus and hyperglycemic complications in bullous pemphigoid

Effect and clinical significance of glucocorticoid on CD4+CD25+ regulatory T cells in patients with hepatitis B virus-related pre-liver failure

To investigate the effect and clinical significance of glucocorticoid on CD4+CD25+ regulatory T cells (Tregs) in patients with hepatitis B virus (HBV)-related pre-liver failure. The subjects of this study included 78 patients with pre-liver failure induced by HBV (cases) and 24 healthy individuals (controls). Among the 78 cases, 42 received glucocorticoid treatment and 36 did not. Between-group differences in Tregs (in peripheral blood) were evaluated by flow cytometry and statistical analysis. Two weeks of glucocorticoid treatment led to an increase in Treg level compared to baseline (before therapy: 2.76 ± 0.73 vs. 3.88 ± 1.60). In addition, after the two weeks of glucocorticoid treatment, the Treg level of improved patients was significantly higher than that measured at baseline (before therapy: 2.70 ± 0.77 vs 3.97 ± 1.59, P < 0.05). Glucocorticoids up-regulate the expression of Treg cells, which may contribute to the immunological mechanism that protects pre-liver failure patients from deterioration of their condition. Careful inspection and monitoring of Treg levels may help improve prognosis of these patients.

Role of ultrasound in the understanding and management of vasculitis

Vasculitis is characterized by a circumferential vessel-wall thickening ('halo'), which can be visualized by modern imaging techniques. In particular, the resolution of ultrasound has increased to 0.1 mm. Ultrasound detects abnormalities that are pathognomonic even in arteries with a diameter below 1 mm. It is particularly helpful in the diagnosis of large-vessel vasculitides, such as classic temporal arteritis, large-vessel giant-cell arteritis (GCA), Takayasu arteritis and idiopathic aortitis. Echocardiography is important for determining cardiac involvement in Takayasu arteritis and also for examining the coronary arteries of children with suspected Kawasaki disease, which is a medium-vessel vasculitis. In small vessel vasculitides ultrasound has only a role for determining the distribution or organ involvement. Fast-track clinics for the diagnosis of GCA help to initiate treatment before complications such as blindness occur; patients receive appointments within 24 h in these clinics. Clinical examination and ultrasound of temporal and axillary arteries are performed by an experienced rheumatologist. In most cases this is able to determine if GCA is present. Temporal artery biopsy can be still carried out in ambivalent cases. The wall swelling of temporal arteries disappears after 2-3 weeks of glucocorticoid treatment. After 3 days of treatment, diagnosis becomes more difficult with ultrasound in some cases. In larger arteries, such as the axillary arteries, wall thickening disappears within months. It tends to be darker (more hypoechoic) in acute disease because of oedema.

High-sensitivity C-reactive protein (hs-CRP) level in children with nephrotic syndrome

The aim of this study was to assess the serum concentration of high-sensitivity C-reactive protein (hs-CRP) in children with nephrotic syndrome (NS) treated with prednisone and cyclosporine A (CyA). Patients were divided into three groups: (I) 20 NS children (aged 4-14 years) in relapse and examined twice, (A) before treatment and (B) after proteinuria regression (a 3-4 week course of prednisone therapy); (II) 20 children with steroid-dependent or steroid-resistant NS, treated with CyA, also examined twice, (D) before treatment with CyA, (E) 6 months after therapy. A control group (C) consisted of 20 healthy children. Serum hs-CRP level was determined by a nephelometric method with a Behring Nephelometer 100 Analyzer, Dade Behring. The results showed that median hs-CRP concentration was the highest in children with relapsing steroid-sensitive NS before treatment (IA). After proteinuria regression (IB), the hs-CRP level had decreased and did not differ from that of healthy controls (C) (P>0.05). In group II, before CyA administration (IID), the level of hs-CRP was normal, but it had increased after 6 months of treatment (IIE) up to a level six-times higher than that of the control group (P<0.01). We concluded that, in children with steroid-sensitive nephrotic syndrome in relapse, the serum hs-CRP level is increased but returns to normal after 3-4 weeks of glucocorticoid treatment. In children chronically treated with CyA due to NS, serum hs-CRP level increases significantly during the therapy.

Increased expression of tissue plasminogen activator messenger ribonucleic acid is an immediate response to parathyroid hormone in neonatal rat osteoblasts.

Osteoblasts have been reported to produce tissue-type (t) plasminogen activator (PA), which may be involved in the initiation of bone resorption via plasmin-metalloproteinase degradation of adjacent extracellular matrix. To investigate this cAMP-activated gene, we characterized the PTH regulation of tPA messenger RNA (mRNA) in neonatal rat osteoblast cultures before and after differentiation in vitro. RNA was purified from cultures at confluence or after treatment with glucocorticoid for 1 week and BGJ/ascorbic acid/beta-glycerophosphate for a second week. Northern blots of total or poly(A)+ RNA were hybridized simultaneously with an oligonucleotide or complementary RNA probe for rat tPA and an oligomeric DNA probe for cyclophilin (CYP), an abundant control gene. Differentiation was monitored by expression of rat osteocalcin mRNA and protein. Both bovine PTH1-34 and forskolin caused an increase in tPA/CYP ratio in the presence of phosphodiesterase inhibitor (IBMX) and cycloheximide (CHX). The effect was maximal (16- to 21-fold increase in tPA mRNA and 6- to 8-fold increase in tPA/CYP ratio) with 25 nM hormone for 6 h and was half-maximally stimulated by 0.75-2.5 nM PTH. The tPA response to PTH was present in first passage osteoblast cultures at confluence and after 1 to 2 weeks of glucocorticoid treatment. Exposure of the differentiated cultures of 1,25-dihydroxyvitamin D (10 nM) for 2 days markedly stimulated osteocalcin mRNA while having no effect on tPA. In Northern blots of poly(A)+ RNA from cultures not treated with CHX, IBMX and PTH (2.5 h) independently stimulated tPA mRNA with no significant effect on CYP mRNA levels. The tPA/CYP ratio increased in five consecutive experiments and the effect of IBMX and PTH were additive. These data indicate that PTH acts via cAMP to stimulate tPA expression by a mechanism that is independent of protein synthesis. The enhancement of PTH action by CHX is compatible with feedback inhibition of tPA transcription by a hormone-activated repressor (which has been proposed to occur in granulosa cells) but effects of CHX on tPA mRNA stability may also occur. Expression of tPA mRNA before and after differentiation may indicate that the enzyme has more than one function.

Acquired pure red-cell aplasia: A consequence of increased natural killer cell activity?

A 19-year-old man with severe pure red-cell aplasia is described. An unusually high proportion of this patient's lymphocytes were large granular lymphocytes (LGL), both in the blood (40%) and in the bone marrow (50%). His blood leukocytes displayed a strongly elevated natural killer (NK) cell activity in vitro against the erythroblastic leukemia line K562. The patient's non-T blood lymphocytes inhibited in vitro erythroid colony formation (BFU-E and CFU-E) but not the granulocyte-monocyte colony growth (CFU-GM) from autologous and allogeneic bone marrow. Neither T-cell-mediated cytotoxicity nor circulating antibodies against erythroid precursors could be demonstrated. The patient's haemoglobin values returned to normal levels after three weeks of glucocorticoid treatment and have since then remained stable with continued prednisone administration. Attempts to reduce the prednisone dose to less than 10 mg/day have led to relapses. It is tempting to suggest that the patient's disease might be caused by hyperactivity of cytotoxic non-T (NK) cells specific for K562 cells and early erythroid precursors.

Glucocorticoid-induced atrophy in different fibre types of selected rat jaw and hind-limb muscles

Six weeks of glucocorticoid treatment (triamcinolone-acetonide-21-phosphate, 1 mg/kg of body weight daily) resulted in a similar pattern of fibre type atrophy in jaw and hind-limb muscles. Fast-twitch glycolytic fibres were significantly atrophied in all muscles investigated. Fast-twitch oxidative glycolytic fibres were affected only in the fast (white) regions of the mixed muscles, while slow-twitch oxidative fibres were unaffected. The results from pair-fed controls (food intake matched to the glucocorticoid-treated animals) showed that the glucocorticoid produced an atrophic response in addition to that produced by the decreased food intake in the experimental animals. These results suggest that the jaw musculature shares the wasting effects induced by elevated circulating glucocorticoid levels often found in stress situations.

Fluctuation of blood-spot 17-OH-progesterone level in infants with congenital adrenal hyperplasia

Serial sampling for determination of 17-OH-progesterone by radioimmunoassay using dried capillary blood spots were performed throughout the day in eight infants with congenital adrenal hyperplasia due to 21-hydroxylase deficiency in order to check the value of a single random sample for identification of patients and in monitoring therapy. The samples were taken in different part of the country and sent into the laboratory by mail. Marked variation of dot-17-OHP values in a range of diagnostic high level was observed before starting therapy without any sign of diurnal rhythm. Repeated sampling for dot-17-OHP during the first weeks of glucocorticoid treatment showed persistent fluctuation at pathological high levels. While receiving glucocorticoid therapy for some months 17-OHP concentrations were suppressed showing moderately elevated levels in the morning and low levels in the evening. The blood-spot 17-OHP method can be used both for early identification and follow-up of congenital adrenal hyperplasia cases, however, 17-OHP profils over 24h are needed for monitoring therapy.