Steroid Dose Reduction Research Articles

Methotrexate in Ulcerative Colitis

There are paucity of data regarding the utility of methotrexate (MTX) in the management of ulcerative colitis (UC). The aim of this study was to describe the efficacy of MTX in achieving steroid-free remission. A retrospective cohort study was conducted using the nationwide Veterans Affairs database to identify steroid-dependent patients with UC using MTX for the period 2001 to 2011. Patients were followed up for 15 months after MTX initiation by tracking their prednisone, MTX, thiopurines, and infliximab dispense. Endpoints were: (1) successful remission, defined as cessation of prednisone filling activity while continuing MTX; (2) failure with continuance, failure to be weaned off steroids while continuing MTX; (3) failure with discontinuance, cessation of MTX while continuing steroids. We included 91 patients with UC with mean age 59 years. The average weekly dose for oral and parenteral MTX was 14 and 25 mg/week, respectively. The average daily dose for prednisone within the oral MTX and parenteral MTX groups was 12 and 25 mg/day, respectively. By the 12th month of follow-up, 37% and 30% of patients on oral and parenteral MTX, respectively, were able to discontinue steroid. There was a nonsignificant trend toward dose reduction of steroids in those who were concomitantly taking oral MTX and steroids. Our study represents the largest cohort of patients with MTX and UC reported to date and suggests that approximately one-third of patients were successfully weaned off steroids with MTX therapy. MTX should be considered in the long-term management of patients with UC on steroids.

AB0346 Safety and efficacy of rheumatoid arthritis treatment with modified-release prednisone (mr-pdn), experience in “real life”.

BackgroundGlucocorticoids (GC) are commonly used for rheumatoid arthritis (RA) treatment with concerns about their side effects. A modified-release formulation of prednisone (MR-PDN) allows the release of the drug during the...

AB0370 An open label trial assessing the efficacy of mycophenolate sodium in active systemic lupus erythematosus patients without renal impairment

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease which is associated with a wide range of clinical, immunological and haematological manifestations. There is an inflammatory response which involves a number...

Adjuvant rituximab therapy in pemphigus: a single-center experience of 18 cases

Background: Pemphigus vulgaris (PV) follows a chronic relapsing course where the mainstay of therapy has been oral corticosteroids and second-line immunosuppressive and immunomodulating therapies. Successful responses have been reported with rituximab, a chimeric monoclonal anti-CD20 antibody targeting B lymphocytes, although its use in recalcitrant pemphigus is still being studied. Methods: A retrospective analysis is presented of 18 patients with cutaneous and mucous membrane involvement after disease relapse following steroid and other adjuvant therapies who were treated with rituximab (4 intravenous infusions of 375 mg/m2 once weekly for 4 consecutive weeks). Results: At 3 months follow-up, 44% (8/18) of cases achieved complete disease remission with a further 44% (8/18) showing partial remission. Further follow-up showed 5/8 partial responders achieving a complete response with 4 cases experiencing disease relapse (72% response at 9 months). There were no adverse drug-related events and its use resulted in a significant reduction in steroid dosage during follow-up. Conclusion: Rituximab is beneficial in the management of refractory PV, resulting in clinical remission and a steroid-sparing effect. Further study needs to examine rituximab dosage and scheduling as well as its place within the treatment algorithm.

A retrospective review of clinical features and treatment outcomes in steroid-resistant interstitial lung disease from polymyositis/dermatomyositis

We reviewed our experience with immunosuppressive agents in patients with steroid-resistant Interstitial Lung Disease in the setting of Polymyositis/Dermatomyositis (PM/DM-ILD) to determine whether there were major differences in outcomes. We identified all patients treated for PM/DM-ILD and assessed cyclophosphamide (CYC), azathioprine (AZA) and mycophenolate (MMF) when used as first-line steroid sparing therapy for effects on pulmonary function variables, dyspnea and tolerance at six and twelve months. Among 46 patients meeting the inclusion criteria, 24 were treated with CYC, 13 with AZA and 9 with MMF. There were no baseline differences between the three treatment groups for any of the demographic or physiologic variables, dyspnea score, the presence of >30% fibrosis on CT, or the baseline steroid dose. At the six months assessment, the overall median change in FVC was 5.0% (25th, 75th percentile -3, 11.5%), corresponding to +.20L (.09, 0.42L) and the DLCO increased by 2.93% (-4, 9%), corresponding to 1mm/ml/Hg (-.58, 2.3). The severity of dyspnea decreased substantially, prednisone dose could be reduced and no important difference in side effects was found in the whole group of patients. This effect was sustained after twelve months of therapy. In patients with PM/DM-ILD related, treatment with CYC, AZA or MMF was associated with stabilization of pulmonary physiology, improved dyspnea, and a reduction of steroid dose.

Characterization and Outcome of Parainfluenza Virus Lower Respiratory Tract Infection After Hematopoietic Cell Transplantation

Abstract 458 Background:Parainfluenza virus (PIV) is one of the most common respiratory viruses causing respiratory symptoms after hematopoietic cell transplantation (HCT); 20–30% of HCT recipients with PIV infection have lower respiratory tract disease (LRTD), associated with high mortality. Although previous studies have reported the outcome and risk factors of PIV LRTD, the definition of PIV LRTD differs in various reports, ranging from patients with radiographically and virologically confirmed cases to cases with only lower respiratory tract symptoms and viral detection from the upper respiratory tract. Here we examined the impact of various manifestations of LRTD, antiviral treatment, and patient and transplant factors on clinical outcome. Patients and methods:This retrospective cohort study included HCT recipients with PIV infection transplanted between 12/1990 and 11/2011 at the FHCRC. PIV infection was defined by detection of PIV in any sample using culture, direct fluorescent antibody testing, and/or polymerase chain reaction. Upper respiratory tract infection (URTI) was defined by PIV detection in nasopharyngeal swab/wash, or sputum without new pulmonary infiltrates. LRTD was divided into 3 groups: possible (new pulmonary infiltrates plus URTI), probable (PIV detection in BAL or biopsy without new pulmonary infiltrates), and proven (new pulmonary infiltrates plus PIV detection in BAL or biopsy). Risk factors for overall mortality were analyzed using Cox proportional hazards models. Results:In 372 patients with PIV infection, median age was 44 years (range, 0–75), and median time to PIV infection after HCT was 69 days (range, 1–2566). Thirty-five (9%) patients had a secondary episode of PIV infection. URTI only, possible, probable, and proven LRTI occurred in 273 (73%), 39 (10%), 7 (2%), and 53 (14%) patients, respectively. In 28 (47%) proven and probable LRTD cases, PIV was first detected in upper respiratory samples a median of 7 days (range, 1–40) prior to detection in BAL or biopsy. Among patients with LRTD, the probability of 90-day survival after PIV LRTD was 47% in proven cases, 57% in probable, and 90% in possible (p < .001; Figure). Comparison between probabilities of 90-day survival after PIV infection in patients with URTI and possible LRTD showed no difference (92% in URTI vs. 90% in possible LRTD, p = 0.67). Cox proportional hazard analysis also showed that proven/probable LRTD resulted in significantly worse survival than URTI (HR, 8.6; 95% CI, 5.0–14.6, p<.001), while possible LRTI did not (HR, 1.2; 95% CI, 0.4–3.4, p=0.74). Multivariable analyses of risk factors for overall mortality among all patients showed that proven/probable LRTD (adjusted HR 7.3, p=<.001), transplantation after 2000 (adjusted HR 0.4, p = 0.002), and steroid administration of more than 1 mg/kg/day pre-LRTD (adjusted HR 2.0, p = 0.02) were significantly associated with mortality. PIV type 3 was significant in the univariable analysis when compared to PIV type 1,2, and 4 combined (HR, 2.51; 95% CI, 1.1–5.8, p=0.03), however, it was not significant in multivariable analysis. Among probable/proven LRTD cases, treatment with ribavirin was not associated with improved survival after adjusting for transplant year, oxygen use, presence of copathogens, donor type, preexisting lung disease and steroid use. High-dose IVIG also did not appear to improve outcome. Conclusions:The outcome of PIV LRTD with viral detection in BAL or biopsy (proven/probable LRTD) was worse compared with that of PIV LRTD with detection in nasopharyngeal samples alone (possible LRTD). Moreover, the outcome of possible LRTD was comparable to that of URTI. Thus, future outcome analyses should consider these disease entities separately. High-dose steroid use was associated with poor survival and neither ribavirin nor IVIG use appeared to be effective in improving overall survival of probable/proven PIV LRTD. Reduction of steroid dose might improve outcome, but further studies are needed to test this hypothesis. New drugs with anti-PIV activity (e.g. DAS181) should be evaluated in this patient population. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Dosage regimen of antenatal steroids prior to preterm delivery and effects on maternal and neonatal outcomes

Objective: The objective of this study was to compare the effects of two betamethasone dosage regimens on selected parameters in mothers and on the status of the preterm newborn. Methods: The analysis included 121 patients who gave birth by gestational week 35 and within 7 days after the completion of a full course of steroid treatment (24 mg). The study group consisted of 45 patients receiving six 4-mg doses of betamethasone every 8 h. The control group consisted of 76 patients receiving two 12-mg doses of betamethasone separated by 24 h. Results: After treatment, a significant increase in the leukocyte count was observed in the control group. Significant reductions in the erythrocyte counts, hemoglobin levels and hematocrit after treatment were also found in the control group. The post-natal status of newborns did not differ significantly between groups. The betamethasone dosage regimen used did not affect the incidence of moderate and severe respiratory disorders, intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy (ROP), infection, hyperbilirubinemia or anemia in neonates. Mild respiratory disorders were slightly more common in the study group. Conclusion: A reduction in the single steroid dose administered to patients at risk of premature birth may reduce maternal side-effects.

Treatment of Acute Visual Loss in Giant Cell Arteritis

Treatment of Acute Visual Loss in Giant Cell Arteritis

Efficacy of Rituximab in Dermatomyositis and Polymyositis Refractory to Conventional Therapy

We report one case of dermatomyositis and one of polymyositis refractory to several conventional inmunosupressive therapies, which present a response after treatment with rituximab, enabling steroid dose reduction and a prolonged remission.

Rituximab in Severe Seronegative Juvenile Myasthenia Gravis: Review of the Literature

Myasthenia gravis is an autoimmune neuromuscular disorder caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction. Awide range of symptomatic therapy with acetylcholinesterase inhibitors and immunotherapy such as corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, plasmapheresis, and intravenous immunoglobulin has been used in the treatment of myasthenia gravis, with variable responses. However, most modalities of treatment involve delayed onset of action. We describe a child with severe, life-threatening seronegative myasthenia gravis who repeatedly failed extubation and responded dramatically to rituximab. She achieved complete and sustained remission for more than 9 months, with gradual reduction in steroid dose without any side effects. Advances in the treatment of myasthenia gravis have reduced mortality and morbidity and improved the quality of life in these patients.

Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy

To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without an increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥ PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤ 46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.

Our experience with rituximab therapy for adult-onset primary glomerulonephritis and review of literature

B cell-targeted immunosuppression with rituximab as primary treatment or when conventional therapy is contraindicated or unsuccessful can induce remission in idiopathic membranous nephropathy (IMN). We explored the efficacy and safety of rituximab therapy in an adult population with IMN and other primary glomerulonephritides. This study is a single-centre retrospective case review of 24 adult patients who received rituximab (RTX) for IMN (n = 11), minimal change disease (MCD, n = 7), focal segmental glomerulosclerosis (FSGS, n = 4), and membranoproliferative glomerulonephritis (MPGN, n = 2). Outcomes included the proportion of patients with complete and partial remission, frequency of relapse, the amount of post-RTX immunosuppression, and toxicity. The median follow-up for all patients was 31.5 months (IQR: 15.0-44.0). Rituximab therapy induced remission in 19/24 (79.2 %) patients (IMN: 63.6 %, MCD: 100 %, FSGS: 75 %, and MPGN: 100 %). Disease recurrence in patients with ≥ 3 relapses pre-RTX therapy (MCD, n = 6 and FSGS, n = 1) decreased from 37.0 to 19.6 events per 1,000 patient-months. All patients with steroid maintenance, discontinued or achieved at least a 50 % dose reduction at 3.0 months (IQR: 1.5-8.0) post-treatment. One patient ceased CSA in addition to a 50 % steroid dose reduction 13 months post-RTX. Rituximab was well tolerated with a single serious infection (4.2 %) responsive to treatment. Rituximab induced remission in IMN comparable with published reports but had an additional benefit in inducing remission in other common glomerulonephritides. Additional randomized studies are needed to confirm its potential therapeutic benefit and optimal dosing for adult-onset primary glomerulonephritis.

Eficacia de rituximab en dermatomiositis y polimiositis refractarias al tratamiento convencional

We report one case of dermatomyositis and one of polymyositis refractory to several conventional inmunosupressive therapies, which present a response after treatment with rituximab, enabling steroid dose reduction and a prolonged remission.

Bevacizumab Improves Quality of Life in Patients with Recurrent Glioblastoma

Objective. To quantify the benefits in survival and quality of life in patients receiving bevacizumab (BEV) for recurrent glioblastoma (GBM). Methods. This is a retrospective study of 40 adult patients with recurrent GBM treated between 2005 and 2009 at a single institution. All patients had initial treatment with surgery, radiation, and concurrent temozolomide, then monthly temozolomide. Over 250 charts were screened. Sufficient data was available for 20 patients treated with BEV and 20 patients who did not receive BEV at the time of recurrence. The independent living score (ILS), designed to reward long-term independent survival, was calculated for each patient. Results. The mean ILS was nearly double in the BEV group compared to the No-BEV group (15.0 versus 8.2, P = 0.002, t-test). Two months after initiation of therapy, the median steroid dose dropped by over 90% in patients treated with BEV, but doubled in the NoBEV group. Median survival from the time of recurrence was significantly affected: 10.6 months in the BEV group versus 4.2 months (P < 0.001, log rank survival) in the NoBEV group. Conclusions. BEV increases independent living and lengthens overall survival after GBM recurrence. Reduction in steroid dose may contribute to prolonged independence.

8748 POSTER Medulloblastoma in Young Adults and Pancytopenia – Treatment Complication or Recurrence?

Background: Malignant gliomas are aggressive primary brain tumours, which include anaplastic gliomas & glioblastoma (GBM). The majority of patients relapse following initial therapy & treatment options are limited. We reviewed patients with recurrent glioma treated with single agent bevacizumab at our centre from May 2009 to Dec 2010. Materials and Methods: Patients were identified from the pharmacy database & their records reviewed. Results: 15 patients were identified; data was available for 12. There were 9 men and 3 women with mean age at diagnosis of 47 (16– 62). Histology at original presentation was GBM in 7 patients, anaplastic astrocytoma in 4 and oligoastrocytoma in 1. All had at least subtotal debulking, with subsequent radiation. In 9 (75%), radiation was concurrent with temozolomide − 8 proceeded to temozolomide alone, 1 patient had progressive disease. 2 (17%) patients had radiation followed by procarbazine, lomustine, vincristine (P.C.V.) − chemotherapy was stopped early in both, due to toxicity in one and progressive disease in the other, this patient then received temozolomide. The 1 patient who originally had an oligoastrocytoma subsequently transformed to GBM, he had radiation followed by temozolomide at that point. Upon progression of disease, 5 patients had further debulking, with insertion of carmustine wafers in 2. Patients started on bevacizumab a median of 16 months from initial diagnosis (5−92), 9 had 10mg/kg 2 weekly, 3 received 7.5mg/kg secondary to performance status concerns. There was a median of 11 cycles administered (1−22). 4 patients are alive, 1 continues on bevacizumab at 4 months, 3 are off treatment due to decreased performance status, at a median 6 months (6−10) from commencing therapy. The other 8 patients died a median of 6 months from starting bevacizumab (1−12). 1 bled into their tumour, 1 had a saddle pulmonary embolism, the remainder died of progressive disease. All patients were on steroid therapy, 7 (58%) had a reduction in steroid dose on bevacizumab. 3 (25%) patients had an improved scan on treatment. The median overall survival was 6 months from commencement of bevacizumab. Conclusion: The management of patients with recurrent malignant glioma is challenging. Despite a median overall survival of 6 months in an unselected cohort, in addition to the ability to reduce steroid dose − which compares reasonably to historical controls -outcome for this group is still disappointing overall. We continue to seek novel therapeutic options for this aggressive disease.

Adalimumab sustains steroid‐free remission after 3 years of therapy for Crohn’s disease

Treatments that achieve sustainable steroid-free clinical remission in Crohn's disease are needed; however, long-term steroid-sparing efficacy data are limited. To evaluate steroid-sparing efficacy and the impact of steroid discontinuation on adverse events during treatment of Crohn's disease with adalimumab in the phase III randomised, double-blind 1-year CHARM trial and for an additional 2 years in its open-label extension ADHERE. Steroid-free remission and response and steroid-sparing (≥50% steroid dose reduction) remission rates were evaluated over 3 years in patients who were taking corticosteroids at CHARM baseline. Of 778 patients randomised in CHARM (including those who did not achieve clinical response to open-label induction therapy), 313 patients (40%) were on corticosteroids at baseline. In the 206 patients randomised to adalimumab, rates of steroid-free remission at 1 year and 3 years were 26% and 23% respectively; corresponding rates were 29% and 25% for steroid-sparing remission and 32% and 28% for steroid-free response. Although the incidence of serious infections with adalimumab treatment during CHARM was higher in patients taking steroids at baseline than those who were not, the rates of overall adverse events, serious infections and opportunistic infections were lower in patients who were able to discontinue corticosteroids than those who remained on steroids. Adalimumab therapy resulted in modest but clinically meaningful rates of steroid-free remission, sustained over 3 years of treatment, in a heavily pretreated population of patients with Crohn's disease receiving steroids at the start of therapy (http://www.clinicaltrials.gov number: NCT00077779).

Response to immunotherapy in CLIPPERS syndrome

Dear Sirs,Chronic lymphocytic inflammation with pontine perivas-cular enhancement responsive to steroids (CLIPPERS) is arecently described treatable, brainstem-predominant, clin-ical and radiological entity [1]. Patients with this conditionpresent with an episodic brainstem syndrome and showcharacteristic scattered and punctate gadolinium (Gd)enhancement in the pons and adjacent CNS structures.They prototypically respond to high dose glucocorticos-teroids and may require chronic steroid or immunosup-pressive treatment, although the effect of intravenousimmunoglobulins (IVIG) in this disease is unknown. Herewe report a patient with CLIPPERS that experienced aclinical rebound of the disease after a short pulse of IVIG.A 28-year-old woman with subacute gait ataxia anddiplopia was admitted to the hospital. Neurologicalexamination revealed internuclear ophthalmoplegia, hori-zontal bidirectional nystagmus and gait and four-limbataxia. Brain and spinal MRI showed multiple punctate Gdenhancing lesions in the mesencephalon, cerebellum andcervical spinal cord. The patient was tested for the presenceof systemic auto-antibodies, anti-neuronal antibodies,infectious pathogens (HIV, T. Pallidum, Brucella spp., B.burgdorferi) and tumoral serum biomarkers. CSF analysisincluded standard biochemistry, cytology and bacteriolog-ical cultures, oligoclonal bands and tests for Tropherymawhippelii and Herpesviridae, with no significant findingsexcept for mildly raised CSF protein. Body-CT and bodyand brain PET-CT were also normal. The patient wastreated with intravenous methylprednisolone for 3 days(1 g/day) followed by oral prednisone tapering startingfrom a dose of 60 mg/day. One week after starting meth-ylprednisolone, she had completely recovered and wascontinued on a slow reduction of oral steroid dose. How-ever, any attempt to taper the oral steroid dose below12.5 mg/day led to neurological relapse of the symptomsand, therefore this dose was maintained for the next6 months. After this period (1 year after disease onset), shewas asymptomatic and physical examination was normal,and therefore treatment discontinuation was reassessed.After she stopped steroids for a few days she suffered arebound of her symptoms: she had new onset mild gaitataxia and brisk symmetric ankle- and knee-jerks. Newbrain and spinal cord MRI disclosed multiple scatteredpunctuate and non-confluent enhancing lesions of a maxi-mum diameter of 0.7 cm visible mainly in the white matterof both cerebellar hemispheres, cerebellar peduncles and inthe cervical spinal cord. (Fig. 1a). At that moment, pontineGd enhancement was relatively scarce compared with thecerebellar hemispheres. Additionally, mild but appreciableamount of diffuse Gd peppering was visible in the whitematter of the whole brain adjacent to the cortico-subcor-tical border. Prednisone dose was increased to 30 mg/dayand the patient recovered to normal in 3 days. Thereafter, a12.5 mg/day dose was maintained for the following9 months and the patient remained asymptomatic. A newMRI 3 months after restoration of steroid therapy showedclear improvement of Gd lesions (Fig. 1b). Notwithstand-ing, steroid side-effects became evident with amenorrhea,hirsutism, mild weight gain and acne. Any attempt to tapersteroid dose below 10 mg/day resulted in a blooming ofneurological symptoms. After assuring 2 weeks of clinicalstability, a short attack pulse of intravenous immunoglob-ulins (IVIG) was administered (0.4 g/kg/day for 5 days)

Clinical efficacy and immunological impact of tacrolimus in Chinese patients with generalized myasthenia gravis

In this multicenter, open-label pilot study, the efficacy, safety, and immunological impact of tacrolimus in Chinese patients with generalized myasthenia gravis are assessed. Forty-seven generalized myasthenia gravis (MG) patients were enrolled into this study and given 3 mg/day tacrolimus for 24 weeks. The primary efficacy measurements used to monitor response to tacrolimus in MG patients were the Osserman grade, the quantitative MG score (QMGS) recommended by the MGFA, the MG-specific manual muscle testing (MMT) score, and the MG-related activities of daily living (MG-ADL) scale. Also, reduction in steroid doses was used to monitor the effect of tacrolimus. Clinical evaluations were conducted at weeks 4, 8, 12, 16, 20, and 24, while immunological parameters were measured at weeks 4, 12, and 24. Measurements of the Osserman grade, QMGS, MMT, and MG-ADL all suggested improvement in patient health by the fourth week of treatment. Steroid dosage was reduced during the course of the study in 74.2% of the forty-three patients who completed the study. There were thirty-one reported adverse events in the study. Only one was considered serious. We found that tacrolimus reduced levels of the IFN-γ, IL-2, IL-10, and IL-13 cytokines and induced the proliferation of tolerogenic plasmacytoid dendritic cells after treatment. Tacrolimus did not change the population of T cell subtypes but did steadily reduce the population of BAFF-R +CD19 + B cells over the course of the study. Our results show that tacrolimus improves the clinical condition of MG patients and is well tolerated. The decrease in IL-13 and reduction of BAFF-R +CD19 + B cells may be related to the therapeutic effect of tacrolimus.

Anti-inflammatory glucocorticoid drugs: reflections after 60 years

This review considers the problem of the serious concomitant side effects of powerful anti-inflammatory drugs modelled upon the principal human glucocorticoid hormone, cortisol. The very nature of the original bio-assays to validate their cortisol-like hormonal and anti-inflammatory activities ensured that pleiotropic toxins were selected for clinical studies. Other complicating factors have been (1) considerable reliance on bio-assays conducted in laboratory animals that primarily secrete corticosterone, not cortisol, as their principal anti-inflammatory adrenal hormone; (2) some differences in the binding of xenobiotic cortisol analogues (vis á vis cortisol) to transport proteins, detoxifying enzymes and even some intra-cellular receptors; (3) the "rogue" properties of these hormonal xenobiotics, acting independently of--but still able to suppress--hormonal mechanisms regulating endogenous cortisol; and (4) problems of intrinsic/acquired "steroid resistance", diminishing their clinical efficacy, but not necessarily all their toxicities. The rather gloomy conclusion is that devising new drugs to reproduce the effect of multi-potent hormones may be a recipe for disaster, in contexts other than simply remedying an endocrine deficiency. Promising new developments include "designed" combination therapies that allow some reduction in total steroid doses (and hopefully their side effects); sharpening strategies to limit the actual duration of steroid administration; and resurgent interest in searching for more selective analogues (both steroidal and non-steroid) with less harmful side effects. Some oversights and neglected areas of research are also considered. Overall, it now seems timely to engage in some drastic rethinking about (retaining?) these "licensed toxins" as fundamental therapies for chronic inflammation.

Benefit and a possible risk of tocilizumab therapy for adult-onset Still’s disease accompanied by macrophage-activation syndrome

We report a 57-year-old female case of intractable adult-onset Still's disease (AOSD). Initial high-dose prednisolone therapy was ineffective, and macrophage-activation syndrome (MAS) manifested after one session of additional tocilizumab therapy. After successful treatment for MAS with lipo-dexamethasone and cyclosporin, tocilizumab therapy aided in the rapid reduction of the therapeutic steroid dose. Tocilizumab may be useful for maintenance therapy for AOSD, although its efficacy is unclear for the highly active phase of the disease.