Reduction In Prednisolone Dose Research Articles

Effectiveness of generic tofacitinib in idiopathic inflammatory myositis (IIM)-a retrospective analysis from Indian Myositis Registry (MyoIN).

Determine domain-based-outcomes and steroid-sparing efficacy of generic tofacitinib in IIM. This is a multicenter retrospective study wherein clinical phenotype, autoantibody profile, prior immunosuppressives, and outcomes at 3, 6, and 12months were retrieved for IIM patients prescribed tofacitinib. Overall clinical response was assessed as complete or partial remission as per physician judgment. Changes in cutaneous and calcinosis domain were recorded as per physician global assessment (PGA), lung domain as per medical research council (MRC) dyspnea scale, and muscle strength by Manual Muscle Testing-8 (MMT-8). Forty-two patients of IIM with mean age 38.7 ± 16years; (76.2% (N = 32) women), median duration of illness 48 (19;88) months were included. Commonest indication for initiating tofacitinib was either for refractory or as steroid sparing for cutaneous domain (N = 25/42, 59.5%) followed by calcinosis (N = 16/42, 38%). Overall complete and/or partial remission was achieved in 23/37 (64.8%), 30/35 (85.7%), and 29/30 (96.6%) patients at 3, 6, and 12months, respectively. At 12-month follow-up, there was a reduction in prednisolone dose, with absolute decrease from a daily dose of 17.5mg (IQR 5;50) to 2.5mg (IQR 0;5) (p < 0.001). Individual domain assessments revealed improvement in cutaneous domain [16/25 (64%)] and calcinosis [6/15 (40%)]. Adverse effects included herpes zoster (N = 2/42, 4.8%) and dyslipidemia (N = 4/42, 9.5%). Treatment with generic tofacitinib significantly reduces the daily dose of corticosteroids and is effective in cutaneous domain including calcinosis in IIM. • This multicenter retrospective study is the first real-world data from India, elucidatingsteroid sparing efficacyof generic tofacitinib in patients with inflammatory myositis. • Domain-based outcome assessment suggests good clinical improvement especially in cutaneous domain, even those with refractory disease. • Modest benefits were evident in calcinosis, but its effect on the muscle and pulmonary domain appears limited.

A placebo-controlled, double-blind study evaluating the effect of orally administered polyunsaturated fatty acids on the oclacitinib dose for atopic dogs.

Supplementation of polyunsaturated fatty acids (PUFA) enables dose reduction of prednisolone and ciclosporin in canine atopic dermatitis (cAD). To determine if oral administration of PUFA reduces the dose of oclacitinib in cAD. Twenty-two client-owned dogs with cAD receiving oclacitinib. Dogs received a fish oil product (PUFA) or paraffin oil (placebo) for 16 weeks. Owners adjusted the oclacitinib dose according to daily pruritus assessments. On Day (D)0, D56 and D112, Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), quality-of-life score (QoL), Global Assessment (GA), quality-of-coat (QoC) and adverse events were recorded. Mean daily oclacitinib dose was significantly reduced in the PUFA group from 0.51 ± 0.20 mg/kg/24 h (D0) to 0.19 ± 0.14 mg/kg/24 h (D85-112; p < 0.00001) and not in the placebo group (D0: 0.70 ± 0.33 mg/kg/24 h; D85-112: 0.53 ± 0.35 mg/kg/24 h, p = 0.5422). CADESI-04 did not change over time or differ between groups. PVAS was significantly lower in the PUFA group (2.8 ± 1.5) compared to placebo (4.2 ± 1.6) at D112 (p = 0.0375). QoL and QoC improved only in the PUFA group (QoL: D0: 20 ± 7, D112: 12 ± 5, p = 0.0057; QoC: D0: 0 ± 0.5, D112: 1 ± 0.5, p = 0.0410). GA on D112 was higher in the PUFA group (p = 0.008). No adverse events were observed. Oral supplementation of PUFA allowed dose reduction of oclacitinib and improved PVAS, QoL, QoC and GA. The use of PUFA is recommended and was safe in the atopic study dogs receiving oclacitinib.

Efficacy and safety of mycophenolate mofetil for steroid reduction in neuromyelitis optica spectrum disorder: a prospective cohort study

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disease that can affect multiple generations and cause complications with long-term prednisolone treatment. This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) in preventing NMOSD relapse while reducing prednisolone dosage. The trial involved nine patients with NMOSD who received MMF along with prednisolone dose reduction. MMF was effective in achieving prednisolone dose reduction without relapse in 77.8% of patients, with a significant decrease in mean annualized relapse rate. All adverse events were mild. The findings suggest that MMF could be a viable treatment option for middle-aged and older patients who require steroid reduction. Clinical trial registration number: jRCT, jRCTs051180080. Registered February 27th, 2019-retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs051180080.

Relapsing cytokine release syndrome in a patient with metastatic renal cell carcinoma treated with pembrolizumab and axitinib therapy.

As immune checkpoint inhibitors become more widely available, the optimal management of immune-related adverse events (irAEs) is becoming increasingly important. Although irAEs are diverse, reports on cytokine release syndrome are rare. Here, we report a case of a 48-year-old man with relapsing cytokine release syndrome after receiving pembrolizumab and axitinib combination therapy for metastatic renal cell carcinoma. During dose reduction of prednisolone for immune-related hepatitis on day 33 after starting pembrolizumab plus axitinib, the patient suddenly developed abdominal pain, and a few hours later became hypotensive and poorly oxygenated. Despite the use of a ventilator and high doses of catecholamines, blood pressure and oxygenation could not be maintained. Extracorporeal membrane oxygenation and intra-aortic balloon pumping were also administered. The cytokine release syndrome (CRS) was treated with tocilizumab, and his general condition improved. Lower-grade CRS relapsed four times despite a moderate dose of oral prednisolone with mycophenolate mofetil or tacrolimus. After gradual reduction in prednisolone over 5months, the patient was discharged from the hospital. Partial remission of renal cell carcinoma continued for 21months, and salvage radical nephrectomy was performed. The patient remained disease-free without the need for further treatment 9months after surgery.

Can Simvastatin Reduce the Need for Immunomodulatory Drugs to Treat Uveitis?: A Prospective, Randomized, Placebo-Controlled Trial

To assess the efficacy of simvastatin 80 mg/day versus placebo in patients with noninfectious nonanterior uveitis receiving prednisolone ≥ 10 mg/day. Randomized, double-masked, controlled trial. Adult patients with noninfectious nonanterior uveitis on oral prednisolone dose of ≥ 10 mg/day. Patients were randomly assigned at a 1:1 ratio to receive either simvastatin 80 mg/day or placebo. A total of 32 patients were enrolled (16 in each arm), all of whom completed the primary end point, and 21 reached the 2-year visit (secondary end points). The primary end point was mean reduction in the daily prednisolone dose at 12 months follow-up. Secondary end points were mean reduction in prednisolone dose at 24 months, percent of patients with a reduction in second-line immunomodulatory agents, time to disease relapse, and adverse events. Our results show that simvastatin 80 mg/day did not have a significant corticosteroid-sparing effect at 12 months (estimate: 3.62; 95% confidence interval [CI]:-8.15 to 15.38; P= 0.54). There was no significant difference between the groups with regard to prednisolone dose or change in dose at 12 and 24 months. There was no difference between the 2 groups in percent of patients with reduction in second-line agent by 24 months. Among patients who achieved disease quiescence, the median time to first relapse was longer for those receiving simvastatin (38 weeks, 95% CI: 14-54) than placebo (14 weeks, 95% CI: 12-52), although this was not statistically significant. There was no significant difference in adverse events or serious adverse events between the 2 groups. Simvastatin 80 mg/day did not have an effect on the dose reduction of corticosteroids or conventional immunomodulatory drugs at 1 and 2 years. The results suggest that it may extend the time to disease relapse among those who achieve disease quiescence. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Initiation of hydroxychloroquine therapy during pregnancy can cause adverse effects and alter pregnancy outcomes: A case of acute generalised exanthematous pustulosis induced by hydroxychloroquine in a patient with systemic lupus erythematosus.

Hydroxychloroquine (HCQ) is effective for treating a number of autoimmune diseases, including systemic lupus erythematosus. HCQ is generally safe and may be prescribed to pregnant women. Although current guidelines recommend initiating HCQ when considering pregnancy, the drug can cause adverse effects such as acute generalised exanthematous pustulosis (AGEP), which should be carefully evaluated. A 30-year-old pregnant woman with systemic lupus erythematosus at 16 + 5 gestational weeks was referred to National Center for Child Health and Development for persistent proteinuria and alopecia. Tacrolimus was initiated, and the dose of prednisone was increased. At 20 + 3 weeks of gestation, HCQ was administered to allow for a dose reduction of prednisolone. Proteinuria gradually improved as the pregnancy course stabilised. At 27 + 1 weeks of gestation, generalised pustular exanthema developed, presumably due to HCQ. Based on the clinical course and the analysis of the skin lesions, she was diagnosed to have either AGEP or generalised pustular psoriasis. Despite discontinuing HCQ, the skin lesions worsened dramatically, and infliximab therapy was required. After one course of infliximab treatment, exanthema gradually subsided. The final diagnosis was AGEP, based on the clinical course and pathological findings. At 30 weeks, pyothorax developed because of the pyogenic skin lesion and the compromised immune system, and long-term antibiotic therapy was required until 32 + 4 weeks, after which she underwent caesarean section. Although introducing HCQ is occasionally necessary during pregnancy, it is preferable to initiate HCQ in the preconception period and not after pregnancy because of the possible adverse effect, which can alter perinatal prognosis. Rheumatologists should consider the potential risks of HCQ.

P60 A case of autoimmune inflammatory myositis in a patient with SLC29A3 spectrum disorder

Introduction/BackgroundThe SLC29A3 gene encodes the equilibrative nucleoside transporter hENT3. SLC29A3 spectrum disorder, an autosomal recessive disorder caused by mutations in this gene, is a rare multisystem disorder resulting in cutaneous manifestations (hyperpigmented, hypertrichotic and indurated patches of skin) and a variety of systemic features, with variable phenotypic expression. Along this spectrum are H syndrome and pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome. The majority of cases reported in the literature have been in patients of Arab descent. We report a case of a patient with SLC29A3 mutation who later developed features of autoimmune disease and myositis.Description/MethodAn 11-year-old girl with an established diagnosis of SLC29A3 mutation, dysosteosclerosis, camptodactyly and type 1 diabetes mellitus presented with a three-week history of intermittent fever, myalgia, muscle weakness and cervical lymphadenopathy. She had a non-specific rash over her eyelids, interphalangeal joints of both hands, torso and limbs. Her movements were restricted due to myalgia. She had no evidence of arthritis. Her creatine kinase was elevated (>1400 units/litre) and MRI of her thighs revealed evidence of myositis not akin to Juvenile Dermatomyositis distribution. An extensive investigation screen showed no evidence of infections. The bone marrow was hypocellular but there was no evidence of malignancy or histiocytosis. An autoinflammatory disease was suspected and the patient was treated with three pulses of IV methylprednisolone, to which she initially responded well but soon relapsed. Anakinra was trialled but this failed as the patient’s daily fevers persisted and her muscle weakness continued to worsen. Methotrexate was commenced and did not result in the desired reduction in prednisolone dose, so the patient was started on 4-weekly infliximab infusions. Following commencement of infliximab, the patient’s fever and rash resolved; her energy levels and muscle power improved and her muscle enzymes began to normalise. Repeat MRI showed her myositis was in remission. Infliximab was stopped after 13 doses due to side effects at the end of the infusions (tachycardia, hypertension and pyrexia). In addition, it was found that she had developed antibodies against infliximab and measured serum drug levels were low. Methotrexate was eventually stopped. The patient is now off all rheumatological treatment (as of February 2019) and she has not had reactivation of any of her symptoms.Discussion/ResultsThe patient we report had insulin-dependent diabetes mellitus, dysosteosclerosis and camptodactyly, three systemic features associated with SLC29A3 mutation. She presented concomitantly with signs of autoinflammatory disease and myositis. While up to 25% of patients with SLC29A3 mutation develop autoinflammatory features, to our knowledge, this is the first reported case of myositis in a patient with this mutation. Both the inflammatory features and myositis resolved following treatment with infliximab infusions. A number of case reports have described successful treatment of inflammation in SLC29A3 mutation with IL-6 inhibitors such as tocilizumab. The complete remission demonstrated in this case following infliximab infusions points to TNF-α inhibition as another potential therapeutic target. It is also interesting to note that our patient is now off all rheumatological treatment, which contrasts with other case reports in the literature where the patients have typically required maintenance immunomodulation therapy to remain asymptomatic. This case may therefore represent a new clinical subtype of SLC29A3 mutation with an autoimmune inflammatory myositis, rather than autoinflammatory as initially suspected, that carries a better prognosis. Further case reports of myositis in SLC29A3 mutation would help to build a clearer picture of its clinical presentation, prognosis and response to biologic therapies.Key learning points/Conclusion1. SLC29A3 spectrum disorder is a rare multisystem disorder that has only recently been recognised. By presenting this case report we hope to increase awareness of this condition and network with other clinicians who have encountered inflammatory disease associated with SLC29A3 mutation, either in their clinical practice or research.2. Up to a quarter of patients with SLC29A3 mutation present with autoinflammatory disease.3. We report on the first case of autoimmune inflammatory myositis in a patient with SLC29A3 mutation, to our knowledge.4. Our patient demonstrated complete remission of her inflammatory disease following treatment with infliximab, which may represent a new clinical subtype of SLC29A3 mutation with an autoimmune, rather than autoinflammatory, myositis that carries a better prognosis.

A real-world study of low-dose thalidomide in severe erythema nodosum leprosum highlighting its mechanistic rationale in a resource-constrained target population.

Corticosteroids remain the main therapy in erythema nodosum leprosum (ENL), and long-term usage in chronic or recurrent ENL is a cause of significant morbidity and mortality. Thalidomide exerts dramatic effect in controlling ENL and helps reduce the dose of steroids, but the cost is a hindrance to its usage. Patients of ENL (steroid naïve and steroid-dependent) were recruited over a 1-year period. An escalating dose of low-dose thalidomide with a reducing dose of prednisolone was titrated depending on the control of disease activity. The primary aim was to reduce the dose of steroids to the lowest effective dose, and the secondary aim was to stop. Sixteen patients of ENL were studied (mean duration of ENL 22.1 months, 15 severe ENL), and a majority (11/16, 68%) were on steroids with a mean duration of 11.27 months. All patients had steroid-related side effects (cushingoid habitus 81.8%, weight gain 54.5%, diabetes mellitus 9%, hyperlipidemia 18.18%, cataract 18.1%, osteoporosis 36.3%, striae 36.3%, acneiform eruptions 18.1%, and myopathy 9%). Steroids could be tapered in a majority of patients (n = 9) within 3 months (mean 2.44 months) with a low dose of thalidomide (25-150 mg/day, mean 78.3 mg) achieving a significant reduction in prednisolone dose (33.16 mg at baseline; 4.28 mg at 3 months, P < 0.05). Steroids could be stopped in 92% of patients by 3.03 months, and both drugs could be stopped in 80% of cases by 5.83 months. The rapid and effective control of ENL with low-dose thalidomide in our series is comparable to the historical efficacy of high-dose thalidomide regimens, making it an affordable therapy in resource-constrained settings and an excellent steroid-sparing agent. The rapid onset of disease control is likely attributable to its action via neutrophils.

Sequential rituximab therapy sustains remission of nephrotic syndrome but carries high risk of adverse effects.

Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome. We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n=127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n=123) managed at one center during 2015-2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs). Sequential RTX therapy, initiated at a median of 10years [interquartile range (IQR) 7.3-14.4], was administered for 1.8courses/person-year [95% confidence interval (CI) 1.7-2.0] over 2.0years (95% CI 1.2-3.0). Therapy was associated with postponement of relapses by a median of 3years in patients with steroid-sensitive disease and 2years in those with steroid resistance. Relapses were reduced by a mean of 2.0relapses/person-year (95% CI 1.8-2.2), enabling a reduction in prednisolone dose to 0.04mg/kg/day (95% CI 0.01-0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20events/person-year (95% CI 0.17-0.23), were chiefly comprised of infusion reactions (n=108) and infections (n=46); serious adverse events were observed in 10.8% patients, at 0.03events/person-year (95% CI 0.02-0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n=52)] than tetanus [65.5% and 34.5% (n=58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of <9-10years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy. Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions.

Treatment options for hypercalcemia after cosmetic oil injections: Lessons from human tissue cultures and a pilot intervention study.

Granuloma formation following self-administered cosmetic oil injections can lead to severe hypercalcemia and renal calcifications due to extra-renal vitamin D activation. This translational study aims to identify Prednisolone sparing therapeutics for hypercalcemia after development of granulomatous disease secondary to paraffin oil injections. Granuloma tissue isolated from five men were cultured ex vivo and treated with selected drugs to block generation of activated vitamin D (1,25(OH)2D3). In a retrospective study, we included data before and during different treatments of 21 men with paraffin oil induced granulomatous hypercalcemia (46 treatment courses) where serum calcium, parathyroid hormone, vitamin D metabolites, creatinine and inflammatory markers were measured. Addition of Ketoconazole or Ciclosporin to granuloma tissue ex vivo culture, significantly suppressed production of 1,25(OH)2D3 after 48h (both p<0.05). Prednisolone was the first treatment option in most men and lowered serum levels of ionized calcium after 1, 2, 3 and 6months compared with baseline (p<0.05). Ketoconazole or Hydroxychloroquine had no significant effect on serum calcium levels and were unable to reduce the concomitant daily Prednisolone doses (p>0.05). Azathioprine did not reduce calcium levels. However, addition of Tacrolimus to Prednisolone treatment enabled a reduction in Prednisolone dose after 3months (p=0.014), but with no additional effect on calcium homeostasis. This study verifies that Prednisolone is an effective treatment and suggests that calcineurin inhibitors may be used as Prednisolone sparing treatment for paraffin oil-induced granulomatous hypercalcemia. Randomized clinical trials are needed to determine clinical efficacy.

Isolated CNS involvement in eosinophilic granulomatosis with polyangiitis treated with mepolizumab: A case report

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis disease involving small-sized vessels. The literature has reported involvement of the central nervous system (CNS) in 5% cases, and isolated CNS involvement is extremely rare. Due to its rarity and scarcity of clinical data, standardized treatment of isolated CNS involvement in EGPA is unclear. Mepolizumab, an anti-interleukin-5 monoclonal antibody, was previously introduced to treat EGPA with longer remission period, more patients showing remission, and reduction in prednisolone dose of those who already taking prednisolone compared to placebo. We describe a case of isolated CNS involvement in EGPA, confirmed by brain biopsy and treated with mepolizumab, which was refractory to conventional immunotherapy.

The feasible maintenance dose of corticosteroid in Takayasu arteritis in the era of biologic therapy

Objective: Although biologic agents are used in Takayasu arteritis (TAK), corticosteroids are still the mainstay of treatment. This study aimed to investigate the feasible maintenance dose of prednisolone (PSL) in the biologic therapy era. Method: We enrolled 93 patients with TAK who satisfied the criteria of the American College of Rheumatology and visited our department from 2008 to 2018. The clinical characteristics and PSL dose of the patients were retrospectively evaluated. Results: The mean ± sd maintenance dose of PSL was 5.0 ± 3.0 mg/day. In patients having TAK for > 20 years, PSL discontinuation and drug-free status were achieved in 27.2% and 18%, respectively. Although tapering the PSL dose to 10 mg/day was achieved within 12 months, tapering to 5 mg/day required 10 years. Relapse significantly interfered with the PSL dose reduction. The clinical characteristics of patients with relapse included a lower rate of combination therapy using immunosuppressants. Moreover, biologics were used in > 60% of patients with relapse. Tapering of PSL was significantly possible in patients receiving biologics and additional relapse was observed in 6.3% and 50% of patients with and without biologics, respectively. Such PSL-sparing effect enabled the reduction of the median PSL dose from 10 to 5 mg/day. Steroid discontinuation was achieved in some patients. Conclusions: The use of biologics significantly reduced the PSL dose in relapsed patients. A PSL dose of ≤ 5 mg/day is a feasible target for TAK, especially when biologic agents are used. Nevertheless, corticosteroid discontinuation may also be the target in some patients.

Osmotic Demyelination Syndrome after Primary Hypoadrenocorticism Crisis Management

Background: Primary hypoadrenocorticism is a rare condition resulting from immune-mediated destruction of the adrenal cortices. It can also occur due to necrosis, neoplasms, infarctions and granulomas. The clinical and laboratory changes are due to deficient secretion of glucocorticoids and mineralocorticoids, which leads to electrolyte disorders associated with hyponatremia and hyperkalemia. These disorders can cause hypotension, hypovolemia and shock, putting a patient's life at risk if inadequate hydroelectrolytic supplementation and hormone replacement is provided. Nevertheless, rapid sodium chloride supplementation is contraindicated due to the risk of central pontine myelinolysis induction. The present study aims to describe a thalamic osmotic demyelination syndrome after management of a primary hypoadrenocorticism crisis in a 2-year-old, female West White Highland Terrier. Case: The patient had a presumptive diagnosis of hypoadrenocorticism already receiving oral prednisolone and gastrointestinal protectants in the last 2 days. After prednisolone dose reduction the dog presented a severe primary hypoadrenocorticism crisis treated with intravenous sodium chloride 0.9% solution along with supportive therapy. Four days after being discharged from the hospital, the patient showed severe neurological impairment and went back to the clinic where a neurological examination revealed mental depression, drowsiness, ambulatory tetraparesis and proprioceptive deficit of the 4 limbs, postural deficits, and cranial nerves with decreased response. Due to these clinical signs, a magnetic resonance imaging was performed. It showed 2 intra-axial circular lesions, symmetrically distributed in both thalamus sides, with approximately 0.8 cm in diameter each without any other anatomical changes on magnetic resonance imaging. The images were compatible with metabolic lesions, suggesting demyelination. Furthermore, liquor analysis did not show relevant abnormalities, except for a slight increase in density and pH at the upper limit of the reference range. After treatment, the patient had a good neurological evolution secondary to standard primary hypoadrenocorticism treatment, without sequelae. Discussion: In the present case report, primary hypoadrenocorticism gastrointestinal signs seemed to be triggered by a food indiscretion episode, not responsive to the symptomatic therapies employed. The patient´s breed and age (young West White Highland Terrier bitch) is in accordance with the demographic profile of patients affected by the disease, where young females are frequently more affected. Regarding the probable thalamic osmotic demyelination syndrome documented in this case, is important to notice that myelinolysis or demyelination is an exceedingly rare noninflammatory neurological disorder, initially called central pontine myelinolysis, which can occur after rapid correction of hyponatremia. It has already been observed in dogs after correction of hyponatremia of different origins, including hypoadrenocorticism and parasitic gastrointestinal disorders. Currently, the terms "osmotic myelinolysis" or “osmotic demyelination syndrome" are considered more suitable when compared to the term "central pontine myelinolysis" since it has been demonstrated in dogs and humans the occurrence of demyelination secondary to the rapid correction of hyponatremia in distinct regions of the central nervous system including pons, basal nuclei, striatum, thalamus, cortex, hippocampus and cerebellum. The present case report emphasizes the difficulties for hormonal confirmation of primary hypoadrenocorticism in a patient already on corticosteroid treatment, as well as proposes that the current term osmotic demyelination syndrome replace the term “central pontine myelinolysis” in veterinary literature related to the management of hypoadrenocorticism crisis.Keywords: Addison Syndrome, hyponatremia, osmotic myelinolysis, magnetic resonance imaging.

Real-World Effectiveness and the Characteristics of a “Super-Responder” to Mepolizumab in Severe Eosinophilic Asthma

Mepolizumab was the first licensed anti-IL5 monoclonal antibody for severe eosinophilic asthma (SEA). To date there are few data to confirm its efficacy in the real-world setting or assessment of baseline characteristics associated with response. How do patients with severe eosinophilic asthma respond to mepolizumab in the real world setting and which characteristics are associated with a super-response to this therapy? We conducted a retrospective review of all patients who received at least 16weeks of treatment with mepolizumab (100mg subcutaneously) for SEA at our regional asthma center in the United Kingdom. Clinical data were collected at each 4-week visit. At 16, 24, and 52weeks, patients were classified as "responders" or "nonresponders." A response was defined as≥50%reduction in exacerbations; for patients whose condition requires maintenance oral corticosteroids (mOCS), a response was defined as≥50%reduction in prednisolone dose. Super responders were defined as exacerbation-free and off mOCS at one year. Ninety-nine patients were included in the analysis. Asthma exacerbations decreased from a baseline of 4.04 ± 2.57 to 1.86 ± 2.17 per year at one year (54%reduction; P< .001). Sixty-eight patients were receiving mOCS at the time of commencing mepolizumab. By one year, the daily median dose fell from 10mg (interquartile range, 10 to 15) to 0mg (interquartile range, 0 to 10; P< .001). Fifty-seven percent of them were able to discontinue mOCS; 72.7%(95%CI, 63.0 to 80.7) of the patients were classified as responders, and 28.3%(95%CI, 20.2 to 38.0) of the patients were classified as super responders. Baseline characteristics associated with responder and super responder status included the presence of nasal polyposis (P= .012), lower baseline Asthma Control Questionnaire 6 (P= .006), a lower BMI (P= .014), and, in those patients receiving mOCS, a significantly lower prednisolone dose at baseline (P= .005). At 16weeks, the one-year responder status was correctly identified in 80.8%patients; by 24weeks, this status rose to 92.9%. In a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI, and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in >90%of patients by week24.

Efficacy of rituximab in difficult-to-manage autoimmune hepatitis: Results from the International Autoimmune Hepatitis Group.

Background & AimsTreatment options remain limited for patients with autoimmune hepatitis (AIH), while there are still concerns over the consequences of long-term corticosteroid use. A few studies have suggested a role for B cell-driven autoimmune liver injury in AIH. This multicentre, international retrospective cohort study from the International Autoimmune Hepatitis Group aims to evaluate the clinical efficacy and safety of rituximab in difficult-to-manage AIH.MethodsClinical data from 22 patients who received rituximab between 2007 and 2017 were collected from centres in the United Kingdom, Germany and Canada. Clinical response was assessed using changes in biochemical and immunological parameters up to 24 months post-rituximab infusion. In addition, we compared the doses of prednisolone used 3 months before and 12 months after treatment, and assessed freedom from AIH flares over the post-treatment period.ResultsTwenty-two patients with type-1 AIH were included, with a median age of 40 years at diagnosis (range 19–79); 15/22 (68%) were female and 18/22 (82%) were Caucasian. The median period from diagnosis to the end of follow-up in these patients was 11 years (range 3–28). Values of alanine aminotransferase, aspartate aminotransferase and albumin improved significantly following rituximab therapy, and were sustained for up to 2 years (all p ≪0.001). Prednisolone doses were significantly reduced by 12 months post-treatment (p = 0.003), with 13/21 (62%) patients having a dose reduction. Over a median post-treatment follow-up period of 6 years (range 1–10), 5 patients developed AIH flares at a median of 22 months post-treatment, giving an estimated 71% freedom from AIH flare at 2 years. Four of these patients received a second course of treatment, of whom 2 had subsequent further flares. No serious adverse events attributable to rituximab were recorded.ConclusionIn patients with difficult-to-manage AIH, rituximab appears to be clinically effective and well tolerated. Rituximab was associated with sustained improvements in serum liver tests, an absence of clinical disease flares, and a reduction in prednisolone dose. Controlled trials are warranted to further evaluate B cell-targeting therapies in patients with AIH.Lay summaryAutoimmune hepatitis is an autoimmune condition of the liver, usually treated with medications that suppress the immune system, such as steroids. However, some patients do not respond to this treatment. We analysed the safety and efficacy of rituximab in patients who were not responding to first- or second-line therapies. Rituximab was safe and improved liver blood tests in 70% of patients over a 2-year follow-up period, while enabling steroid doses to be reduced in two-thirds of patients, which is a very positive clinical outcome.

Successful management of severe asthma in a young boy with eosinophilic chronic rhinosinusitis who received omalizumab: a case report

BackgroundThe incidence of chronic rhinosinusitis with nasal polyps has recently increased in Japan and other East Asian countries, and this disease is called eosinophilic chronic sinusitis (ECRS) in Japan. ECRS usually occurs in adults and is frequently accompanied by refractory bronchial asthma. However, its occurrence in children under 10 years of age is rare. Here, we present an unusual case of ECRS complicated by intractable asthma in an 8-year-old boy.Case presentationOral administration of prednisolone (10 mg/day) initially relieved the ECRS and bronchial asthma, but both returned during prednisolone dose reduction. Because nasal cavity-opening surgery was ineffective, oral administration prednisolone at 10 mg/day was continued. Pancytopenia was observed 16 months after the start of treatment, and the patient was admitted to our hospital. He was diagnosed with refractory cytopenia in childhood, but gradually improved after cyclosporine treatment. Although the dose of cyclosporine was therapeutic for asthma, it did not alleviate the asthma attacks, and the patient’s quality of life markedly decreased. We administered omalizumab even though its use was contraindicated by negative results in an inhalable antigen test. After the third administration of omalizumab, the asthma was better controlled and respiratory function improved; however, the nasal symptoms of ECRS persisted. Attempts to relieve these symptoms by increasing the therapeutic dose of omalizumab were only partially successful. We replaced omalizumab with mepolizumab; doing so slightly improved the sinusitis symptoms, but quality of life remained unsatisfactory. We repeated the nasal cavity-opening surgery. After surgery, the asthma and sinusitis were unchanged.ConclusionsOmalizumab effectively treated the severe combined asthma in a young patient, but its effect on sinusitis was insufficient. More cases and long-term follow-up data are needed to better evaluate the effectiveness of mepolizumab for treatment of ECRS.

Use of mycophenolate mofetil and azathioprine for the treatment of chronic hypersensitivity pneumonitis-A single-centre experience.

The optimal pharmacological management of chronic hypersensitivity pneumonitis (cHP) is unknown. Corticosteroids are often used as first line therapy but can be associated with side effects. There is a paucity of data examining the role of steroid-sparing agents in cHP. We aimed to determine the effect of mycophenolate mofetil (MMF) and azathioprine (AZA) on lung function and prednisolone dose in cHP patients. Retrospective analysis of patients initiated on either MMF or AZA following a multidisciplinary team diagnosis of cHP. Changes in lung function and prednisolone dose up to 12months before and after MMF/AZA initiation were analysed. Twenty two out of 30 patients remained on treatment at 12months (18 MMF, 4 AZA). Steroid-sparing therapy resulted in a significant reduction in prednisolone dose from 16.2±9.7 to 8.2±4.2mg daily (P=0.002). Treatment with MMF or AZA for 12months was associated with a significant improvement in carbon monoxide diffusing capacity (TLCO) (-0.55±0.96 vs. +0.31±0.58mmol/kPa/min, P=0.02). Although treatment reduced the rate of forced vital capacity decline (-111±295 vs. +2.3±319mL), it was not significant (P=0.22). MMF or AZA therapy in cHP is associated with an improvement in TLCO and reduction in prednisolone dose. There is a need for prospective trials.

9. Successful use of IL-6 pathway blockade to treat autoinflammation occurring in the context of a novel TNFRS1A gene mutation

IntroductionAutoinflammatory fever syndromes are rare and present significant diagnostic and treatment challenges. We present a case which illustrates some key concepts regarding the diagnosis and treatment of a patient with an autoinflammatory disorder, and also touches on the management of active autoinflammation in pregnancy.Case descriptionA 29-year-old woman with a recently identified autoinflammatory disorder was referred to the local rheumatology service in September 2018. She reported having been symptomatic of fever, rashes and arthralgia since the age of 10, and TNF receptor 1 associated periodic syndrome (TRAPS) was suspected on the basis of an N71 deletion on axon 2 of the TNFRS1A gene when tested by a national reference centre 9 months previously.At the time of presentation she was 25 weeks into her sixth pregnancy, the first with a new partner. She reported significant pregnancy morbidity having given birth to a daughter with multiple congenital abnormalities who unfortunately died two days after birth. She suffered 4 subsequent miscarriages at 5-7 weeks gestation with the same partner and underwent extensive genetic testing. At her initial review in the obstetric clinic, she was already receiving low-molecular-weight heparin with aspirin. Colchicine 1 mg tds, did not confer significant symptomatic benefit.One month later, with careful counselling about pregnancy exposure to this biological treatment, IL-1 receptor antagonist (anakinra) therapy was instituted but discontinued after three weeks for generalised rash, as well as lack of efficacy manifesting in raised inflammatory markers. Infection was excluded during a subsequent hospital admission, and prednisolone treatment resulted in significant improvement in clinical course and acute phase response. The patient gave birth to a healthy infant at 37 weeks’ gestation.In the postpartum period, a recurrence of symptoms was observed. IL-6 receptor antagonist (tocilizumab) treatment was commenced at 12 weeks postpartum but discontinued owing to reports of sore throat, cough, headache and fever on the day of the injection. The patient had also discontinued prednisolone on the day of the injection and tocilizumab was rechallenged with good symptomatic response, normalisation of inflammatory markers, and successful reduction in prednisolone dose.DiscussionThis case highlights some interesting points with relation to the treatment of autoinflammatory disorders refractory to IL-1 pathway blockade, and also, of the management of flares of autoinflammation during pregnancy.Firstly, this lady failed to respond to IL-1 receptor antagonist anakinra which has been associated with efficacy in several reports for individuals with TRAPS, and has supplanted TNF blockade with agents such as etanercept for this condition. Only a handful of case reports describe successful IL-6 inhibitor administration for this condition, and this merits further study. This patient’s flare of autoinflammation was treated in the post-partum period, but the demographic characteristics of the autoinflammatory diseases are such that people of child-bearing age may be required to receive treatment in order to prevent pregnancy morbidity as a result of uncontrolled inflammation. IL-6 blockade has not to date been associated with adverse pregnancy outcomes, although this data requires extension and validation. 2 cases of renal agenesis have been reported in children born to mothers with anakinra, but the very small numbers of exposed parents warrants further examination of this observation and the careful study of ongoing pharmacovigilance data to explore this observation.Secondly, success with IL-6 inhibition has been reported in a series of patients with familial Mediterranean fever, the most common autoinflammatory disorder, but this treatment does not feature in the most recent European guidelines for this condition. IL-6 inhibition is well-established in the treatment of adult-onset Still’s disease (AoSD) however, and this lady’s presentation shares important features with that condition. The existence of TNF-receptor 1 mutations has been reported in patients with AoSD, and it may be that this patient’s presentation is more akin to adult-onset Still’s disease and that her TNF receptor mutation is an incidental finding.Key learning pointsThis report adds to the handful cases in which IL-6 blockade has been used successfully to treat the autoinflammatory manifestations of suspected TNF receptor 1 associated periodic syndrome (TRAPS) after the failure of IL-1 receptor blockade with anakinra.Careful history and examination are required to differentiate between potentially overlapping symptoms of drug reaction, autoinflammation, and infection in patients with systemic autoinflammatory disorders (SAIDs). Once a history consistent with autoinflammatory flare was established, cautiously rechallenging with an IL-6 pathway inhibitor ensured this effective treatment was not discounted due to concerns over a drug reaction.With a degree of commonality between the more common conditions in the SAID family, a detailed examination of the clinical phenotype is essential to the interpretation of genetic tests used for the diagnosis of TRAPS and related disorders.Uncontrolled inflammatory disease is associated with pregnancy morbidity and very limited information is available about the short and long-term safety of treatments for autoinflammatory diseases in general. Current guidelines do not recommend the use of IL-6 inhibitor therapy in pregnancy.Conflict of interestThe authors declare no conflicts of interest.

Hydroxychloroquine Improves the Disease Activity and Allows the Reduction of the Corticosteroid Dose Regardless of Background Treatment in Japanese Patients with Systemic Lupus Erythematosus.

Objective Hydroxychloroquine (HCQ) was not approved in Japan until 2015, and its therapeutic potential has not been explored in depth. We evaluated the additional therapeutic effect of HCQ in Japanese patients with systemic lupus erythematosus (SLE) on maintenance therapy. Methods Patients with SLE who visited our hospital from 2015 to 2016 and were taking prednisolone (PSL) at <20 mg/day were retrospectively evaluated. All patients were divided into three groups according to their maintenance treatment regimen: PSL + immunosuppressant, PSL alone, and no treatment. We compared the changes in the SLE disease activity index (SLEDAI), PSL dose, and cumulative flare rate between patients who were and were not treated with HCQ. Results Among the 165 patients evaluated, 35 (21.2%) were treated with HCQ. The mean period of observation did not differ markedly between patients who did and did not receive HCQ (p=0.3). The SLEDAI and PSL dose were significantly reduced in patients who received HCQ, regardless of their background treatment regimen. The cumulative flare rate was lower in patients who received HCQ than in those who did not in the PSL + immunosuppressant and no maintenance treatment groups (p=0.03 and 0.05, respectively). Conclusion The addition of HCQ reduced the disease activity and allowed PSL dose reduction, regardless of background treatment, in Japanese patients with SLE.

Adalimumab for the treatment of refractory active and inactive non-infectious uveitis

Background/aimsTo compare the efficacy of adalimumab in eyes with active and inactive non-infectious uveitis in the real-world setting.MethodsMulticentre, retrospective, chart review of patients with refractory non-infectious uveitis treated with adalimumab....