Low-dose Prednisolone Research Articles

Efficacy of Levamisole in children with Frequent Relapsing and Steroid Dependent Nephrotic Syndrome at Tertiary Care Center-Karachi.

Objectives:To determine the effectiveness of levamisole in maintaining remission of proteinuria in children with frequent relapsing and steroid dependent nephrotic syndrome (FR/SDNS).Methods:This observational study on 81 children with FR /SDNS was carried out from June 2007 - June 2017 at The Kidney Center-Postgraduate Training Institute, Karachi-Pakistan. Levamisole (leva) along with low dose prednisolone on alternate day (AD) was used after induction of remission with daily oral prednisolone in children with FR/ SDNS for 6-36 months. Patients with steroid resistance were excluded. Data was analyzed using descriptive statistics.Results:Eighty-one patients with FR (66) or SD (15) received levamisole treatment. Mean age at diagnosis was 3.72 ±2.33 years. Levamisole was used on AD in 59.25% and daily in 40.74% of cases. Twenty-four could not complete six months and were excluded, 57 patients completed treatment duration of 15.68±9.93 months and 51 post-leva follow-up of 11.70±11.23 months. Mean leva-dose was 1.73±0.67 mg/kg/ patient. Mean cumulative prednisolone dose per patient before, on-leva and post-leva was 3389.81±2785.22, 2471.97±2024.98 and 661.37± 905.37 mg respectively. Mean relapse rate per year before leva, on -leva and post -leva was 3.30 ±0.50,0.98± 1.1and 0.79±1.27 respectively. Levamisole was effective in 90% of patients. During post-leva follow up, 76.4% patients, maintained remission, whereas 23.5% behaved as FR/SD and require further immunosuppressive therapy.Conclusions:Levamisole was effective in maintaining remission in 90% while on treatment, whereas it maintained remission after discontinuation in 76.4% cases. Levamisole may be used as first steroid sparing agent before other immunosuppressive therapies in children with FR/SDNS. Further studies are required for optimal duration and dosage schedule.

Steroid-sparing effect of omalizumab in stage IV (corticosteroid dependent) allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) consists of five stages ranging from the acute stage (pulmonary infiltrate, eosinophilia, and increased total Immunoglobulin-E [IgE]) to pulmonary fibrosis. Our patients were diagnosed as Stage IV (corticosteroid dependent) ABPA, in which treatment with systemic corticosteroids cannot be discontinued as symptoms worsen after discontinuation of oral corticosteroids. Omalizumab is a humanized recombinant, monoclonal antibody that selectively binds to IgE to inhibit the immune response to an allergen. It forms immune complexes which not only lower the level of free IgE antibody, but also serve as an allergen buffer, even in cases of markedly high serum IgE >1000 IU/ml in ABPA. In this article, we report three cases of (Stage IV) corticosteroid-dependent ABPA with poor clinical response even after effective treatment with antifungal therapy and courses of corticosteroids (>3 exacerbations/year). After the start of injection omalizumab, the three patients have experienced significant and sustained clinical improvement and improved quality of life with low-dose prednisolone 5 mg every alternate day. The dose of systemic corticosteroids was reduced by 50% in the 1st year and by 70% in the 2nd year although lung function failed to improve.

Prospects for Treatment of Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) is a disease related to anti-aquaporin-4 antibody. Since NMOSD was once considered a phenotype of multiple sclerosis, no approved drugs are available for its treatment. In Japan, the current standard treatment for preventing relapses in patients with NMOSD is low-dose prednisolone and/or oral immuno-suppressants. There is a critical unmet need for non-steroid treatments for patients with NMOSD. Four monoclonal antibodies have completed their clinical trials in Japan and are pending approval. In this review, we summarize the results of each of these clinical trials.

Tubulointerstitial nephritis with monotypic lympho-plasmacytic infiltrates in a patient with primary Sj\xf6gren\u2019s syndrome accompanied by IgA-type monoclonal gammopathy

BackgroundAlthough most cases of tubulointerstitial nephritis in paraproteinemia are monoclonal light chain deposition-mediated, interstitial nephritis as neoplastic interstitial cell infiltration has rarely been described. On the other hand, lympho-plasma-cell-rich tubulointerstitial nephritis, in which the infiltrative cells are usually polytypic, is often evident in primary Sjögren’s syndrome (pSS). Herein we present a rare case of pSS in a patient who had been diagnosed as having IgA kappa-type monoclonal gammopathy of undetermined significance (MGUS) and developed tubulointerstitial nephritis with monotypic (IgA kappa) lympho-plasmacytic infiltrates.Case presentationA 74-year-old Japanese woman with pSS who had been diagnosed as having IgA kappa-type MGUS developed progressive renal dysfunction. Renal biopsy revealed tubulointerstitial nephritis with abundant plasma cell-rich mononuclear cell infiltrates without atypia. Immunohistochemical staining for immunoglobulins and light chains showed that most infiltrates were positive for IgA and kappa. Most of the infiltrative cells were positive for CD38 and CD138, and cells positive for CD 19 and CD 45 were also widely evident. Electron microscopy and immunofluorescence studies revealed no apparent immunological deposits in the glomeruli and tubules. Bone marrow and whole-body radiological examinations revealed no findings suggestive of multiple myeloma or lymphoma. Renal function improved rapidly with prednisolone 40 mg daily and has been maintained at the same level on low-dose prednisolone and azathioprine for 18 months.ConclusionTubulointerstitial nephritis with monotypic cell infiltrates, without immunological deposits, is a quite rare histological picture in MGUS, and might be a unique renal manifestation in patients with pSS.

Muktwelve: A Randomized Phase II Trial of Selinexor, Cyclophosphamide and Prednisolone Vs Cyclophosphamide and Prednisolone in Relapsed or Refractory Multiple Myeloma (RRMM) Patients

Background Triplet combination therapies are the preferred treatment choice for RRMM, however, high-cost-high-cost drug combinations pose significant barriers for health technology assessments (HTA) and access in many public healthcare systems, including the UK. Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1), thereby forcing the nuclear retention of key tumour suppressor proteins (TSPs), leading to MM cell death. Recently, the FDA has granted accelerated approval to selinexor for MM on the basis of results from the STORM trial, which tested selinexor in doublet combination with dexamethasone in RRMM. Several trials exploring triplet combinations are ongoing, but most are with high-cost combination partners. In the Myeloma UK Twelve (MUKTwelve) trial Selinexor is combined with low-dose cyclophosphamide and prednisolone in a randomized phase II design, exploring a triplet regimen that could potentially be more accessible for wider patient population. Study design and methods MUKtwelve is a randomized, controlled, open, parallel group, multi-centre phase II trial designed to evaluate clinical efficacy of selinexor in combination with cyclophosphamide and prednisolone (SCP) in patients with RRMM (ISRCTN15028850). The primary objective is to determine whether the addition of selinexor to cyclophosphamide and prednisolone (CP) may lead to increased progression free survival (PFS) compared to historic CP data. A calibration arm of patients will receive CP alone, and will be used to evaluate the validity of the outcome in the experimental arm in comparison to historical control data. Participants who experience disease progression on the CP arm may, if deemed eligible receive SCP. Eligible participants are those with RRMM who have received ≥ 2 prior anti-myeloma treatments including a proteasome inhibitor and lenalidomide. Entry criteria are inclusive to allow for a real-world RRMM population, including GFR >=20, no limitation regarding pre-existing polyneuropathy and allowance of growth factor and transfusion support. A maximum of 60 participants will be recruited (45 participants in the SCP arm, and 15 in the CP arm) from 10 UK NHS hospitals. Participants are randomized on a 3:1 basis to receive either SCP or CP. The trial opened on 20th July 2018 and as of 23rd July 2019 16 patients have been randomized. Trial treatment is as shown in Table 1 (28 day cycle). Metronomic, continuous doses of cyclophosphamide and intermittent doses of prednisolone in conjuncture with proactive, prophylactic side effect management, in particular nausea and kachexia, have been chosen to make the trial more accessible for a wider RRMM population. The primary endpoint is proportion of patients alive and progression-free at 6 months (PFS6m). Secondary endpoints include response, response duration, safety and toxicity, PFS and treatment compliance. A three outcome statistical design is used based on the SCP arm only. The trial is designed to test the hypothesis PFS 6m ≤0.28 vs. PFS 6m ≥0.44 (equivalent to median PFS 3.3 vs. 5.1 months). With 90% power, 1-sided 10% significance level, a total of 45 patients are required in the SCP arm. Cut-off values and conclusions for the three outcome design: ≤14/45 patients PFS6m, SCP does not warrant further study≥17/45 patients PFS6m, sufficient evidence for further study of SCP15 or 16/45 patients PFS6m, decision uncertain and can be based upon other secondary endpoints. This approach provides more realistic decision-making compared to those where success of failure is hinged on a difference of a single primary endpoint event. Discussion The MUKtwelve trial is the first trial to assess the clinical efficacy of selinexor with low-dose cyclophosphamide and prednisolone in RRMM, a triplet regimen that, if found to be effective, is likely to be accessible to a wider patient population. Disclosures Brown: Amgen, Celgene, Janssen, Karyopharm: Other: Research funding to Institution. Hall:Celgene, Amgen, Janssen, Karyopharm: Other: Research funding to Institution. Kendall:Karyopharm: Other: Research funding to Institution. Ingleson:Karyopharm: Other: Research funding to Institution. Flanagan:Amgen, Celgene, Janssen, Karyopharm: Other: Research funding to Institution. Auner:Karyopharm: Consultancy; Takeda: Consultancy; Amgen: Other: Consultancy and Research Funding. Boyd:Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Garg:Janssen: Honoraria; Janssen, Takeda, Novartis: Other: Travel expenses; Novartis, Janssen: Research Funding. Kaiser:Celgene, Janssen: Research Funding; Takeda, Janssen, Celgene, Amgen: Honoraria, Other: Travel Expenses; Abbvie, Celgene, Takeda, Janssen, Amgen, Abbvie, Karyopharm: Consultancy.

332.9: Decision making in an adolescent requiring emergent heart transplant – Is HLA matching relevant?

Background: A 17-year old boy with Ebstein’s anomaly of tricuspid valve, severe biventricular dysfunction and class IV heart failure was admitted for pre-heart transplant evaluation (HT). Three days later, he had sudden cardiac arrest and revived with CPR and placed on VA ECMO. Attempts at ECMO wean were unsuccessful due to RV dysfunction. Pre-transplant work up showed acute kidney injury (AKI) and otherwise he was deemed an eligible recipient for emergent heart transplantation. Luminex® single antigen bead test was negative for Class I and Class II HLA antibodies. On ECMO day 5, a suitable donor was available. HLA typing of donor and recipient revealed 4 out 6 mismatch. Luminex DSA cross match was negative. Two doses of intravenous Basliximab (20 mg each) were used for induction therapy. Post operative graft function was excellent, and surveillance endomyocardial biopsies done on day 7 and day 21 were negative (ISHLT Grade 0 ACR; pAMR0; C4d and CD68 negative on IHC). He was discharged home on post-operative day 29 with oral Tacrolimus, Mycophenolate Mofetil and low dose prednisolone. He continues to do very well on follow up at 1 year. Luminex DSA continues to be negative for Class I and Class II antibodies. Discussion: Children with heart failure bridged to mechanical circulatory support are at high risk for early graft rejection after HT. Emerging crossmatch methods and HLA typing are crucial to improve organ allocation and achieve better match to recipients of HT. Extensive HLA antigen polymorphism, donor shortage and logistics and ischemia time are some of the limiting factors to derive better HLA compatability. HLA matching increases graft survival and reduce the incidence of graft rejection. HLA-DR mismatch is independently associated with ACR at 1 year and predicts long term survival in HT. Graft survival increased with fewer HLA-DR mismatches [0–1 vs. 2 mismatches: risk ratio (RR) = 1.09 (95% confidence interval (CI): 1.01–1.19; P = 0.04)]. Although our patient has several risk factors (pre-transplant ECMO, emergent listing, complicated hospital course) for successful outcome, having fewer HLA DR mismatch and negative DSA at 1 year follow up is encouraging.

Membranous nephropathy with solitary polyclonal IgA deposition: A case report andliterature review.

A 60-year-old man presented with nephrotic syndrome (NS). Light microscopy of renal biopsy specimens showed minor glomerular abnormalities, while immunofluorescence microscopy revealed solitary polyclonal granular IgA deposition along the glomerular capillary walls. Electron microscopy showed small amounts of electron-dense deposits in the subepithelial area, but not in the mesangial area. In this patient, apparent underlying disease was not found during the 3-year follow-up, and low-dose prednisolone was effective in the treatment of NS. To our knowledge, there is only one case report of membranous nephropathy with clinicopathological features similar to our case.

Single-Arm Non-Blinded Multicenter Clinical Trial on T-Cell-Replete Haploidentical Stem Cell Transplantation Using Low-Dose Antithymocyte Globulin for Relapsed and Refractory Pediatric Acute Leukemia.

Although approximately 70% of pediatric hematological malignancies are curable, approximately 30% remain fatal. No standard treatment is available in patients showing relapse and those with refractory disease. Although different methods are adopted in different hospitals, its efficacy is extremely limited. In recent years, haploidentical stem cell transplantation, involving high-dose cyclophosphamide administration post-transplanta tion, has been used, mainly in adults; however, its application is limited to removal of alloreactive T cells. Multicenter single-arm clinical trials of T-cell replete haploidentical stem cell transplantation (TCR-haplo-SCT) will be conducted in children with relapsed and refractory acute leukemia. After myeloablative conditioning using total body irradiation or busulfan, intensive graft versus host disease prophylaxis is administered, consisting of low-dose rabbit anti-human thymocyte globulin, tacrolimus, methotrexate, and prednisolone. An external control group is set up for the study. The treatment period is around 3 months, and the follow-up period is 2 years from transplantation completion.The aim of this study is to verify the efficacy and safety of TCR-haplo-SCT and present it as a new immune cell therapy for improving survival rate in children with relapsed and refractory acute leukemia.

Adrenal insufficiency in kidney transplant patients during low-dose prednisolone therapy: a cross-sectional case-control study.

Maintenance immunosuppressive regimens after renal transplantation (RTx) most often include prednisolone, which may induce secondary adrenal insufficiency, a potentially life-threatening side effect to glucocorticoid (GC) treatment due to the risk of acute adrenal crisis. We investigated the prevalence of prednisolone-induced adrenal insufficiency in RTx patients receiving long-term low-dose prednisolone treatment. We performed a case-control study of patients on renal replacement therapy differing in terms of GC exposure. The study included 30 RTx patients transplanted >11 months before enrolment in the study and treated with prednisolone (5 or 7.5 mg prednisolone/day for ≥6 months) and 30 dialysis patients not treated with prednisolone. Patients underwent testing for adrenal insufficiency by a 250-µg Synacthen test performed fasting in the morning after a 48-h prednisolone pause. Normal adrenal function was defined as P-cortisol ≥420 nmol/L 30 min after Synacthen injection. This cut-off is used routinely for the new Roche Elecsys Cortisol II assay and is validated locally based on the Synacthen test responses in 100 healthy individuals. Thirteen RTx patients {43% [95% confidence interval (CI) 27-61]} had an insufficient response to the Synacthen test compared with one patient in the control group [3% (95% CI 0.6-17)] (P = 0.0004). Insufficient responses were seen in 9/25 and 4/5 RTx patients treated with 5 and 7.5 mg prednisolone/day, respectively. We found a high prevalence of adrenal insufficiency among RTx patients receiving low-dose prednisolone treatment. We therefore advocate for increased clinical alertness towards prednisolone-induced adrenal insufficiency in RTx patients and thus their potential need of rescue GC supplementation during stress.

16. TB or not TB? A mistaken case of SAPHO in a 65 year old male

IntroductionSAPHO is a rare syndrome of osteoarticular disorders with associated skin manifestations. The classic constellation of symptoms includes synovitis, acne, pustulosis, hyperostosis and osteomyelitis. Estimated prevalence is 1-4/10,000, but the syndrome is underdiagnosed due to its variable presentation and lack of formal diagnostic criteria. SAPHO is a diagnosis of exclusion and conditions such as infectious osteomyelitis and bone tumours must be eliminated first. We present a case of SAPHO, mistaken for spinal tuberculosis (TB).Case descriptionA 67-year-old Caribbean man with a history of type 2 diabetes mellitus and multiple prolapsed discs requiring surgical fixation presented in 2014 with severe back pain, swinging fevers and weight loss. A CT scan showed sclerosis of T9/10 vertebrae with corresponding bone oedema on an MRI spine. He commenced induction treatment for TB based on radiological features and travel history. Two months later, an MRI spine showed progressive inflammation at T10/11. Blood and tissue samples were negative for acid fast bacilli. Mycobacterium cultures, Interferon-gamma release assay (IGRA) and PCR were negative. However, treatment for TB was continued for a further ten months. Three months later, he re-presented with thoracic back pain and night sweats. MRI showed new inflammation at T6/7 and L3/4 reported as probable osteomyelitis. IGRA, blood and tissue cultures remained negative. Meanwhile, the patient suffered nine episodes of synovitis affecting knees and wrists. Knee X-rays showed end-stage hypertrophic osteoarthritic changes with severe osteophytosis. Synovial biopsies showed inflammatory changes but no evidence of TB.The patient re-presented in 2018 with back pain, sternoclavicular (SC) joint tenderness, painful knee swelling, night sweats and weight loss. Blood and synovial fluid cultures were negative, with calcium pyrophosphate crystals detected in synovial fluid. USS scan of the SC joint showed floridly active right-sided synovitis and synovial thickening on the left. CRP was 350 and he was treated with broad spectrum antibiotics for two weeks for presumed septic arthritis. Rheumatology review was requested when he failed to improve. His constellation of symptoms (synovitis, hyperostosis, osteitis and a history of a pustular rash) suggests a diagnosis of SAPHO. He commenced a weaning prednisolone regime and given zoledronic acid to good effect. Recurrence of symptoms occurred at low dose prednisolone, so he was given IM steroids and commenced on methotrexate.DiscussionSAPHO is underdiagnosed due its variable presentation and the need to first exclude infection and malignancy. The patient’s radiological features consistent with spinal TB and risk of TB exposure delayed diagnosis, despite negative serology and cultures.It is important to be aware that the full constellation of symptoms may not be evident at the time of presentation, or indeed at all in the course of the condition; our patient reported a prior history of a pustular rash on the soles of his feet, although there was no clinical evidence of this at the time of review. Involvement of classically affected joints, including anterior chest wall and thoracic spine, or skin involvement should increase clinical suspicion of SAPHO. NSAIDs and corticosteroids are first line therapy, with DMARDs, biological agents and bisphosphonates used to maintain remission. Key learning pointsPractitioners must consider the possibility of SAPHO, particularly in those with symptoms of osteomyelitis but no identifiable pathogen or who do not respond to antibiotic therapy. High inflammatory markers or high fevers do not preclude its diagnosis. As such, it is important to exclude infection, including osteomyelitis and septic arthritis, and malignancy prior to making a diagnosis.Clinicians should also be aware that the patient may not present with the full SAPHO syndrome; close review of past medical history and questioning about unreported episodes of synovitis or rash may be required to make the diagnosis.Conflicts of interestThe authors have declared no conflicts of interest.

42. Large vessel vasculitis with rapidly expanding aortic aneurysm

IntroductionThis case report describes the delay in diagnosis and potentially life-threatening complications of a patient with large vessel vasculitis.The initial diagnosis was of vascular Ehlers-Danlos Syndrome, based on family history and imaging. However, recurrent episodes of chest pain and a rapidly expanding aortic aneurysm prompted further diagnostics which led to the diagnosis of giant cell arteritis with large vessel vasculitis. The patient required thoracic surgery due to expansion of the aortic aneurysm. This case demonstrates the risk of delaying the diagnosis of large vessel vasculitis and the complexities of immunosuppression in the context of major surgery.Case descriptionA previously fit and well 69-year-old man presented with constitutional symptoms and intermittent chest pain for six months. Two months after symptom onset, he was admitted with chest tightness and shortness of breath. He had raised inflammatory markers with thrombocytosis and was given antibiotics for a probable chest infection.A CT pulmonary angiogram revealed ascending aorta dilatation, 47mm with wall thickening. The radiologist reported this as being most likely due to systemic hypertension. There was no evidence of malignancy on abdominal and pelvic imaging. The aortic changes were attributed to possible underlying Ehlers-Danlos syndrome, as his daughter had a diagnosis of Ehlers-Danlos Type III. He was discharged despite persistently raised inflammatory markers and no positive microbiology.He was readmitted after six weeks with pyrexia and severe chest pain. A CT of his thoracic aorta showed further expansion of the aortic aneurysm, 59mm with a slightly thickened abdominal aorta wall. With a rapidly expanding aortic aneurysm and persistent raised inflammatory markers, the suspicion of large vessel vasculitis was raised. No symptoms of cranial temporal arteritis or polymyalgia rheumatica. A FDG-PET scan showed high uptake in the ascending, thoracic and upper abdominal aorta in keeping with extra-cranial large vessel vasculitis. He was treated with IV methylprednisolone for three days with subsequent oral prednisolone. Whilst on high dose glucocorticoids, he developed steroid induced diabetes and hypomania hence oral methotrexate 15 mg once weekly was added.The cardiothoracic team elected to delay cardiothoracic surgery until he was on less than 15 mg of oral prednisolone daily. However, reduction of oral prednisolone led to a flare of giant cell arteritis. The patient had to undergo elective aortic valve and ascending aorta replacement whilst on 40 mg of prednisolone. Tocilizumab was added two months after surgery and prednisolone was successfully reduced to 3mg.DiscussionCritically, appropriate treatment was delayed due to misdiagnosis of Ehlers-Danlos Syndrome; this was largely based on the family history. This red herring likely distracted clinicians from seeking a better explanation for the patient’s presentation and aortic changes.The initial oral steroid course was complicated by steroid induced complications and pending cardiothoracic surgery. The surgical team planned to delay surgery until the patient is on a lower prednisolone dose, due to the increased risk of infection and poor wound healing. The patient therefore had a rapid steroid tapering regime, reducing by 5mg two-weekly, from a starting oral dose of 65mg. Such rapid steroid tapering carries a risk of disease flare, and in fact two weeks prior to surgery, his inflammatory markers rose, and his prednisolone dose had to be increased from 25mg to 40mg.A collaborative decision between the rheumatologists and surgeons was then made to proceed with surgery despite the high-dose steroids, as simultaneous inflammation control and prompt surgical repair took precedence over the potentially increased post-operative risks.The patient also experienced steroid-related side-effects, but the switch to steroid-sparing agents was challenging. Starting tocilizumab as a further immunosuppressant had to be delayed until after surgery, as IL-6 inhibition would distort C-reactive protein as a measure of both disease activity and potential post-operative infection.In summary, this case highlights the difficulty in diagnosing large vessel vasculitis and the potential delay in treatment can cause significant morbidity and mortality.Appropriate imaging is crucial to ascertain a diagnosis of large vessel vasculitis. Immunosuppression must be tailored individually, accounting for side-effects and competing risks.Points for discussion include the use of newer imaging modalities in diagnosing large vessel vasculitis and monitoring disease activity. The efficacy and safety of tocilizumab as a steroid-sparing agent for this condition should also be investigated.Key learning pointsThe importance of early diagnosis and treatment in patients with large vessel vasculitis, as vascular complications can arise if treatment is delayed.The use of appropriate imaging modalities such as MR angiogram and FDG-PET is crucial for diagnosis of large vessel vasculitis.Glucocorticoid therapy is the mainstay treatment for large vessel vasculitis, but side-effects can be limiting. Steroid sparing agents, such as IL-6 inhibitors should be considered early as an alternative immunosuppressant for patients with large vessel vasculitis.Careful planning of immunosuppression is required prior to major surgery.Conflicts of interestThe authors have declared no conflicts of interest.

A Swedish register-based, long-term inception cohort study of patients with rheumatoid arthritis - results of clinical relevance.

PurposeAt the end of the twentieth century, the outcome of rheumatoid arthritis (RA) was shown to be unsatisfactory and new therapeutic strategies were introduced. This initiated a register-based long-term study of early RA, the Better Anti-Rheumatic PharmacOTherapy (BARFOT) study. The aims were to evaluate the disease course and to acquire knowledge for improved care.Patients and methodsBARFOT is a multicentre observational study of patients with early RA, consecutively included 1992–2006. The patients are followed in daily practice according to a structured protocol for 15 years and data recorded in a web-based register. Also, through linkage of the BARFOT register to national registers we have acquired information on comorbidity and mortality.ResultsIn all, 2857 patients have been included and over 80 scientific articles have been published. Phenotypic characteristics at disease onset, i.e. gender, smoking habits and autoantibody profiles have been addressed. The disease course over 15 years was described. Early predictors for persistent disease activity, impaired function, joint damage and co-morbidities have been identified. Treatment strategies have been studied. A randomized sub-study gave strong support for the treatment of recent RA with low-dose prednisolone in combination with disease-modifying anti-rheumatic drug. Furthermore, the impact of lifestyle factors, such as smoking, alcohol consumption, body weight and physical activity has been addressed.ConclusionA register-based study like BARFOT has provided a basis for optimal long-term management of patients with RA. In addition, the register has made it possible to perform a diversity of studies of RA addressing various issues of major relevance to the patients.

55. A case for continuing tocilizumab beyond 12 months in giant cell arteritis?

55. A case for continuing tocilizumab beyond 12 months in giant cell arteritis?

8. An autoinflammatory syndrome resembling Castleman’s disease with excellent response to IL-6 blockade

Introduction Autoinflammatory diseases are an emerging group, characterised by recurrent inflammatory episodes due to dysregulated innate immunity. Common features include fevers, rash, arthralgia, lymphadenopathy and systemic symptoms. Castleman’s disease is a rare lymphoproliferative disease, associated with the overproduction of interleukin-6 (IL-6). Its two main variants: unicentric and multicentric differ in aetiology and clinical outcomes. The cytokine storm driven by IL-6 can mimic autoinflammatory disease. We present the case of an acquired autoinflammatory syndrome in a 33-year-old male with the clinical phenotype of Castleman’s but no culprit lymph node detected radiologically. Symptoms dramatically improved with yocilizumab, an IL-6 blocker.

SAT-078 OUTCOMES WITH LOWER VERSUS HIGHER STARTING TACROLIMUS DOSING IN KIDNEY TRANSPLANT RECIPIENTS

The SYMPHONY study established low dose tacrolimus, mycophenolate, prednisolone and IL-2 receptor antagonist induction, as standard of care for immunosuppression in kidney transplant recipients (KTRs). In our service, we reduced the starting tacrolimus dose from 0.075mg/kg BD (higher dose (HD)) to 0.05mg/kg BD (lower dose (LD)) to minimise supratherapeutic tacrolimus levels in the early post-transplant period. The aim of our study was to compare the LD and HD starting tacrolimus regimens in KTRs with respect to achieved tacrolimus levels and clinical outcomes.

SAT-005 PLA2R+VE MEMBRANOUS GLOMERULONEPHRITIS PATIENTS SHOWS POOR RESPONSE TO TACROLIMUS PLUS PREDNISOLONE THERAPY COMPARED TO PLA2R-VE PATIENTS

Idiopathic Membranous Nephropathy (IMN), an autoimmune concomitant nephrotic syndrome of the adult is mainly associated with PLA2R antibody expressed on podocytes. The lack of exact mechanisms involved in the pathogenesis of IMN is transmitted to its therapeutic management. There is no standard therapy for patients with frequent relapsing or steroid-dependent IMN. Hence we propose the efficacy of low dose Tacrolimus (Tac) plus prednisolone and associated changes in anti-PLA2R in adult IMN. Total 101 membranous nephropathy patients were treated with combination of prednisolone 1mg/kg alt-day) and Tac 0.1mg/kg/day (trough 6-10 ng/ml first 6M and 4-6 ng/ml for next 3M) then both taper by 1/3 every month up to 12M. Out of 101 patients, 15 diabetic, 7 lupus, 1HBV and 1 ankylosing spondylitis patients were excluded. Finally, 77 Patients were followed and evaluated for the anti-PLA2R level at baseline, 3M, 6M,12M and end of follow-up (17-61 , median 38 months). CR, PR, relapse, and side-effects were recorded. Of the 77 patients, at 3M 60(77.92%; CR-37, PR-23); at 6M 61(79.22%; CR-53, PR-8); at 12M 53(68.86%; CR-47, PR-6) achieved remission. Eight (10.38%) relapsed and 16(20.77%) showed no response at 12M. At end of follow-up, out of 54 responsive patients 37(68.51%; CR-36, PR-1) remained in remission and 17(31.48%) patients relapsed. Out of 77 patients, 51 (66.3%) were anti-PLA2R positive. Remission rate was significantly low in PLA2R+ve than PLA2R-ve (36/51 vs 24/26; p=0.03) at 3M, (36/51 vs 25/26; p=0.009) at 6M and (31/51 vs 22/26; p=0.03) at 12M. PLA2R level was decreased by 60.38% and 77.56% at 3M and 6M respectively. There were significant correlations between PLA2R level and 24h proteinuria at baseline, 3M and at 6M. (Figure-1) During therapy 4 patients develop cutaneous tenia, 1 osteonecrosis of the femur head, 1 corpus tunnel syndrome, 4 onset diabetes, 3 tremor, and 14 patients experienced GI symptoms. The eGFR was decreased significantly (p=0.003) by 26.5% at the end of therapy and was normalized after stopping Tac, and 5 non-responsive patients had doubling of serum creatinine and progressively deteriorated eGFR. To note, 4 females had pregnancy and successful delivery in our cohort of patients. PLA2R+ve patients showed poor response compare to PLA2R-ve patients. Remission with Tacrolimus and prednisolone therapy is comparable to historical Ponticelli (Pred plus CYP) regimen. Successful pregnency was ovserved on Tac based regimen.

PS1491 PLATELET KINETICS IN PATIENTS WITH CHRONIC IMMUNE THROMBOCYTOPENIA TREATED WITH THROMBOPOIETIN RECEPTOR AGONISTS

Background:Chronic immune thrombocytopenia (ITP) is characterised by antibody‐mediated platelet destruction, shortened platelet survival (PS) and impaired platelets production. Platelet kinetic study (PKS) assesses in vivo the mean PS, platelet production and the platelet sequestration site. Thrombopoietin receptor agonists (TPO‐RA) increase platelets counts (PC) in majority of chronic ITP patients. Moreover, some patients could retain stabile response after TPO‐RA discontinuation, which is attributed to the immunomodulatory effects of the drugs. Addressing this issue only a few studies have been done assessing the effect of TPO‐RA on PKS parameters.Aims:To evaluate the effects of TPO‐RA on PKS parameters.Methods:Ten patients with chronic ITP, median age 55.3 years (range 12–72), gender (f: n = 7, m: n = 3), splenectomised 6/10, were treated with TPO‐RA (eltrombopag, n = 7, romiplostim, n = 3). Response was assessed according to the criteria of the International Working Group (IWG) on ITP. Autologous 111Induim‐oxinate‐labeled PKS were performed in all patients before and 5 months after TPO‐RA therapy initiation.Results:A good treatment response was achieved in 8/10 of patients (eltrombopag, n = 6, romiplostim, n = 2). Two refractory patients were treated with TPO‐RA and low dose prednisolone. Baseline median parameters were as follows: PC 6.5x109/L (range 1–17), PS 0.5 days (range 0.1–1.6, normal: 7–10), platelet production ratio 0.65 (range 0.01–3.2, normal 1 ± 0.2), platelet turnover 30875 Plt/μL/day (range 1731–103500). The post−treatment PKS showed significantly higher median PC of 62.5x109/L (range 5–501) (p = 0.013) and median platelet production ratio of 1.8 (range 0.5–37.9) (p = 0.05). However, median PS of 0.7 days (range 0.1–2.9) (p = 0.09), as well as platelet turnover of 58471.5 Plt/μL/day (range 2800–462236) (p = 0.086) and platelet destruction site remained unaltered. It is of note that two refractory patients (N08 and N010 in table) increased their platelet production (platelet production ratio and platelet turnover), while their PS remained reduced. It is of note that there was no clear correlation between PC and PS. Nevertheless, PC correlated only with platelet turnover prior (p = 0.006) and after TPO‐RA therapy (p = 0.029).Summary/Conclusion:Our prospective study in which PKS was performed initially and during TPO‐RA therapy suggests that TPO‐RA could increase PC by augmented production. Further studies on larger cohorts are needed to confirm this idea.image

Relationships between concomitant biologic DMARDs and prednisolone administration and blood tacrolimus exposure or serum CYP3A4/5-related markers in rheumatoid arthritis patients

BackgroundThis study aimed to evaluate the relationships between concomitant biologic disease-modifying anti-rheumatic drugs (DMARDs) and prednisolone administration and blood tacrolimus exposure or serum CYP3A4/5-related markers in rheumatoid arthritis (RA) patients without severe disease activity. MethodsForty-six RA patients treated with oral tacrolimus once daily for maintenance of clinical remission to moderate disease activity were enrolled. The blood concentrations of tacrolimus and its major metabolite were determined at 12 h after the evening dosing. Blood samples for determination of serum markers including 4β-hydroxycholesterol (4β-OHC), 25-hydroxyvitamin D (25-OHD) and interleukin-6 (IL-6), and CYP3A5 genotype were collected. ResultsMost enrolled patients had RA with clinical remission to mild disease activity. Concomitant tocilizumab or low-dose prednisolone administration did not alter the blood tacrolimus exposure. Serum 4β-OHC level was lower in tocilizumab co-treated patients than in the biologic DMARD non-treated patients. The blood tacrolimus concentration was inversely correlated with the serum level of 25-OHD, but not 4β-OHC and IL-6. The serum level of 4β-OHC was positively associated with that of 25-OHD. No correlations were observed between the serum levels of CYP3A4/5 activity markers and IL-6. The patients with the homozygous CYP3A5*3 had the higher blood tacrolimus concentration, while CYP3A5*3 allele was not associated with the serum levels of 4β-OHC and 25-OHD. ConclusionsConcomitant use of tocilizumab or low-dose prednisolone had no effect on the pharmacokinetics of tacrolimus, while tocilizumab lowered serum 4β-OHC. Blood tacrolimus exposure was negatively associated with serum 25-OHD in RA patients with clinical remission to moderate disease activity.

Is Palindromic Rheumatism a Pre-rheumatoid Arthritis Condition? Low Incidence of Rheumatoid Arthritis in Palindromic Rheumatism Patients Treated with Tight Control Strategy.

Palindromic rheumatism (PR) is characterized by repetitive, afebrile episodes of acute arthritis and peri-arthritis. The aim of this study was considering the long-term outcomes of patients with PR who were treated with tight control strategy using Disease-modifying anti-rheumatic drugs (DMARDs). We reviewed the charts of 106 patients diagnosed with PR who were referred to the Connective Tissue Diseases Research Center (CTDRC). We recruited all the patients diagnosed with PR according to the criteria of Hannonen. They visited the CTDRC clinic regularly and were treated with hydroxychloroquine and low dose prednisolone because of active episodes of PR. In cases that the attacks did not come under control in 3-6 months, methotrexate was added or replaced and the dose was increased up to 25mg/week. In resistant cases, sulfasalazine was added, followed by the addition of leflunomide and then azathioprine. Disease outcome was evaluated by getting complete or partial remission and prevention of disease evolution to rheumatoid arthritis (RA) or other inflammatory connective tissue diseases. This study included 92 patients with PR who were treated with DMARDs. Attacks were controlled completely or partially in 76 (82.6%) patients. Medications free remission was obtained in 16.3% of the patients. RA developed in 8.7% of the patients. By multivariate logistic regression analysis, age ≤40 at disease presentation, non-adherence to therapy and PIP joints involvement were the only factors which independently predicted the risk of treatment failure. Tight control strategy by using DMARDs may control PR and prevent disease progression to RA.

Immune-mediated cholangiopathies : Diagnostic and therapeutic challenges

Immune-mediated cholangiopathies comprise primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and IgG4-associated cholangitis (IAC). Acommon feature is the progressive destruction of bile ducts leading to cholestasis with fibrosis and cirrhosis of the liver over time. The diseases are mostly identified during routine laboratory testing. Clinical signs and symptoms such as pruritus, fatigue or jaundice are infrequent in the early stage. The diagnostic work-up involves the patient's history, physical examination, serological tests, abdominal ultrasonography, magnetic resonance cholangiopancreatography (MRCP) and, where necessary, liver biopsy and genetic testing. Ursodeoxycholic acid (UDCA) is an effective treatment of PBC. Second-line therapies in addition to UDCA for incomplete UDCA responders are obeticholic acid (OCA) and bezafibrate, whereby only OCA has received approval for this indication from American (Federal Drug Administration) and European (European Medicines Agency) authorities. In PSC, UDCA improves prognostic markers; dominant bile duct strictures are treated with endoscopic balloon dilatation. Despite therapy, liver transplantation is frequently necessary for PSC. The risk of developing cholangiocarcinoma, colon cancer, and gallbladder cancer is increased for patients with PSC. In contrast to PBC and PSC, IAC responds well to corticosteroids. Disease relapse, however, is common, making long-term treatment with low-dose prednisolone or azathioprine necessary.