Steroid-sparing Effect Research Articles

Infliximab versus interferon-alpha in the treatment of Behçet's Syndrome: Clinical data from the BIO-BEHÇET'S randomised controlled trial.

Whilst biologic therapy is used for Behçet's Syndrome of all subtypes refractory to first-line immunomodulation, there has been an absence of high-quality evidence-and no predictive biomarkers to optimally inform choice. BIO-BEHÇET'S was a randomised, controlled, head-to-head clinical trial comparing the two most frequently used biologics in active refractory Behçet's. Bayesian-designed, pragmatic, standard of care, two-arm, parallel head-to-head trial at four UK centres. Patients with active disease randomised to infliximab or interferon-α2a, and received follow-up with symptom-directed examination at Weeks 12 and 24. Primary outcome was Behçet's Disease Activity Index (BDAI) at 12 weeks. Secondary outcomes included BDAI at 24 weeks and significant improvement in individual organ systems, including ocular symptoms, oral and genital ulcers, arthritis pain, quality of life, disease activity, and steroid use. Biomarkers were also investigated but are reported elsewhere. 79 patients were recruited. Both treatments were equally effective, with a mean difference of 0.13 in BDAI (80% CI: -0.19, 0.46). No significant differences were observed for secondary outcomes, though there were clinically significant within-group reductions for each over time. A modest steroid-sparing effect was observed, with complete cessation of steroids in 20% and 44% of those randomised to infliximab and interferon-α2a, respectively. There was a trend for minor benefit in favour of infliximab in terms of tolerability and persistence. In this first reported, high-quality, head-to-head trial of two biologics in Behçet's, both infliximab and interferon-α2a showed comparable short-term clinical efficacy and safety in refractory active disease of all subtypes. EudraCT: 2014-005390-36; ISRCTN: ISRCTN49793874.

Long-term Corticosteroid Treatment Patterns and Steroid-sparing Effects of Approved Treatments for Generalized Myasthenia Gravis in the United States

Long-term Corticosteroid Treatment Patterns and Steroid-sparing Effects of Approved Treatments for Generalized Myasthenia Gravis in the United States

Clinical outcomes of tocilizumab therapy in polyarticular and systemic juvenile idiopathic arthritis: a single-center analysis (2018-2022)

AbstractThis single-center retrospective study aimed to evaluate the safety and efficacy of Tocilizumab (TOC) in children with polyarticular (pJIA) and systemic juvenile idiopathic arthritis (sJIA) who exhibited inadequate responses to disease-modifying antirheumatic drugs (DMARDs) and biological modifiers (bDMARDs). Conducted at the Department of Pediatric Rheumatology, National Institute of Geriatrics, Rheumatology, and Rehabilitation in Warsaw, Poland, between 2018 and 2022, the study enrolled 29 patients diagnosed with JIA based on International League of Associations for Rheumatology (ILAR) criteria. The cohort comprised 13 sJIA and 16 pJIA patients, aged 2-18 years, receiving TOC treatment for 24 months. Safety and efficacy assessments included analysis of medical documentation, laboratory tests (CRP, ESR, WBC), and Juvenile Disease Activity Score (JADAS) 71 at baseline, 3, 6, 12, and 24 months post-treatment initiation. Significant reductions in CRP and ESR levels were observed within three months, with sustained improvement in JADAS71 scores over the 24-month treatment period. A substantial majority, 73.07% of patients, achieved inactive disease status or low disease activity, highlighting T0C’s effectiveness. Adverse effects were manageable, predominantly involving mild to moderate infections, with no serious adverse events or instances of macrophage activation syndrome (MAS). The study also noted a steroid-sparing effect of TOC, with a reduction in glucocorticoid usage among the cohort. Tocilizumab demonstrates substantial efficacy in reducing disease activity and improving clinical outcomes in patients with pJIA and sJIA, coupled with a favorable safety profile. These findings reinforce the role of TOC as a critical component of the therapeutic arsenal for JIA, offering hope for improved quality of life and disease management in this patient population.

A real-life experience with eculizumab and efgartigimod in generalized myasthenia gravis patients

IntroductionEculizumab, a complement active antibody, and efgartigimod, an Fc fragment that blocks neonatal Fc receptor, are both approved to treat generalized myasthenia gravis (gMG) patients. The objective of this study is to describe the clinical response to both treatments in a real-life setting.MethodsWe collected baseline and follow-up clinical data using the Myasthenia Gravis-Activities of Daily Living (MG-ADL), and Quantitative Myasthenia Gravis (QMG). We included 63 patients, 32 treated with eculizumab and 31 with efgartigimod. Of the efgartigimod-treated patients, 22 were anti-acetylcholine receptor antibody-positive (AChR-Ab +) and 9 were AChR-Ab- (3 MuSK-Ab + and 6 seronegative).ResultsBoth treatments showed similar efficacy relative to the MG-ADL scale reduction (p = 0.237). Efgartigimod had a similar effect on both AChR-Ab + and AChR-Ab- (p = 0.280). Eculizumab was superior to efgartigimod relative to the QMG score reduction for the entire dataset (p = 0.003) and was more likely to achieve a clinical response at the QMG compared to efgartigimod (OR 1.373; p = 0.016). Steroid-sparing effect was higher for eculizumab than efgartigimod ( – 16.7 vs – 5.2 mg of the baseline daily dose at follow-up; p = 0.001). Mean speed of prednisone reduction was – 13.1 mg of the daily dose for each month of follow-up for eculizumab-treated patients and – 3.2 for efgartigimod (p = 0.001). We found three serious events, all not related to treatment in the investigator’s opinion. One eculizumab-treated patient experienced a severe pneumonia and died despite treatment.ConclusionsOur study provides evidence that eculizumab and efgartigimod can be used in clinical practice to reduce disability in gMG patients. Eculizumab-treated patients had a higher QMG response and steroid sparing effect. Efgartigimod may offer a more flexible schedule due to its cyclical use, no need for vaccination, and efficacy in AChR-Ab- patients.

United States clinical practice experience with eculizumab in myasthenia gravis: symptoms, function, and immunosuppressant therapy use

Background/objectivesThe phase 3 REGAIN study and its open-label extension demonstrated the efficacy of the complement C5 inhibitor eculizumab in patients with treatment-refractory, acetylcholine receptor antibody–positive generalized myasthenia gravis (gMG). The aim of the ELEVATE study was to assess the effectiveness of eculizumab in clinical practice in adults with MG in the United States.MethodsA retrospective chart review was conducted in adults with MG who initiated eculizumab treatment between October 23, 2017 and December 31, 2019. Outcomes assessed before and during eculizumab treatment using a pre- versus post-treatment study design included Myasthenia Gravis–Activities of Daily Living (MG-ADL) total scores; minimal symptom expression (MSE); physician impression of clinical change; minimal manifestation status (MMS); and concomitant medication use.ResultsIn total, 119 patients were included in the study. A significant reduction was observed in mean MG-ADL total score, from 8.0 before eculizumab initiation to 5.4 at 3 months and to 4.7 at 24 months after eculizumab initiation (both p < 0.001). At 24 months after eculizumab initiation, MSE was achieved by 19% of patients. MMS or better was achieved by 30% of patients at 24 months. Additionally, 64% of patients receiving prednisone at eculizumab initiation had their prednisone dosage reduced during eculizumab treatment and 13% discontinued prednisone; 32% were able to discontinue nonsteroidal immunosuppressant therapy.DiscussionEculizumab treatment was associated with sustained improvements in MG-ADL total scores through 24 months in adults with MG. Prednisone dosage was reduced in approximately two-thirds of patients, suggesting a steroid-sparing effect for eculizumab.

Role of extracorporeal photopheresis in the management of acute and chronic graft versus disease: current status.

Extracorporeal photopheresis (ECP) is a therapy that combines the collection of mononuclear cells by apheresis, the addition of a photosensitizer (8-methoxisoralen), the illumination of the product with ultraviolet A light, and the immediate infusion of the product to the patient. Initially developed and approved to treat T-cell cutaneous lymphomas, soon started to be used to treat graft versus host disease (GvHD) developed after allogeneic hematopoietic-cell transplantation. The high response rate of ECP in skin, ocular, oral, pulmonary, and liver forms of chronic GvHD, the steroid-sparing effect, and the improved overall survival of treated patients, made ECP one of the second-line treatments used to treat steroid-resistant acute and chronic GVHD. Recently, the development of new drugs for treating GVHD has changed the position of ECP in the therapy of GVHD and has started to be used in combination with drugs for increasing the response rate to the treatment in severe or resistant forms of acute and chronic GVHD. ECP remains an essential therapeutic resource in the management of patients with refractory acute and chronic GVHD.

Update on targeted treatments for ANCA-associated vasculitis

Targeted therapy has revolutionized the management of ANCA-associated vasculitis (AAV) over the last fifteen years. Rituximab, an approved induction and maintenance agent for severe AAV, is no less effective than cyclophosphamide as induction therapy and particularly useful in relapsing or refractory disease, or in women. In patients with relapsing AAV, granulomatosis with polyangiitis or PR3-ANCA, it is more effective than cyclophosphamide. Rituximab maintenance is superior to the conventional immunosuppressive drugs that it replaces. Low-dose preemptive rituximab infusions are recommended every 6months for 18months, followed by re-evaluation to decide whether 4 additional biannual infusions should be administered, balancing the probability of relapse and the risk of serious infections on rituximab. A growing body of experimental and clinical data shows that C5a pathway inhibition is a promising therapeutic option for AAV, which could reduce glucocorticoids needs. Avacopan is a first approved oral C5A receptor antagonist, used when there is a high risk that glucocorticoids will cause serious adverse events. In eosinophilic granulomatosis with polyangiitis, the importance of IL-5 for eosinophil activation and survival led to evaluation and approval of mepolizumab, a humanized monoclonal antibody directed against IL-5. Mepolizumab showed a steroid-sparing effect. Its effectiveness in active vasculitis remains uncertain and is currently being evaluated. Benralizumab targeting the IL-5 receptor was recently shown to be noninferior to mepolizumab. Rituximab has had disappointing results in non-severe active vasculitis and is being evaluated as maintenance therapy. Plasma exchange is not indicated as first-line treatment but remains recommended when creatinine levels exceed 300μmol/L.

Clinical Outcome of Vitamin D Supplementation in Moderate and Severe COVID-19 Patients: A Randomized Clinical Trial

The COVID-19 pandemic has posed a major global health challenge, especially for individuals with underlying health issues. This study aimed to assess the clinical outcomes of vitamin D supplementation in patients with moderate to severe COVID-19 in a tertiary care hospital through a randomized clinical trial. Sixty-two SARS-CoV-2 positive patients were enrolled and divided into intervention (vitamin D supplementation) and control groups. Key findings include: The intervention group showed a significant reduction in the need for supplemental oxygen therapy by day 14. Vitamin D supplementation had a steroid-sparing effect, with fewer patients in the intervention group needing steroids compared to the control group. Patients in the intervention group experienced better clinical outcomes, with reduced ICU transfers and shorter hospital stays. A significant decrease in inflammatory markers, specifically ferritin and D-dimer levels, was observed in the intervention group by day 14. Despite these improvements, no significant correlation was found between vitamin D supplementation and overall mortality rates. The study concluded that vitamin D supplementation could be a beneficial adjunctive treatment for managing moderate to severe COVID-19, potentially improving clinical outcomes and reducing healthcare burdens. However, further research with larger sample sizes is needed to validate these findings and establish comprehensive guidelines for vitamin D use in COVID-19 treatment protocols. This abstract provides a concise summary of the study, outlining the purpose, methodology, key findings, and conclusions, reflecting the content of the research accurately.

Mycophenolate Mofetil with Steroid, a Reasonable Alternative to Current First-line Therapy, for Idiopathic Membranous Nephropathy in Resource-constrained Settings: A Randomized, Open-label Study.

The modified Ponticelli regimen (mPR) is a first-line therapy in patients with idiopathic membranous nephropathy (IMN); however, it has a less favorable safety profile. Though mycophenolate mofetil (MMF) + steroid (S) is not recommended by Kidney Disease Improving Global Outcomes guidelines, it can be used as an alternative to mPR due to higher tolerability and steroid-sparing effect. Thus, we compared the safety and effectiveness of MMF + S and mPR regimens in patients with IMN. This randomized, open-label study enrolled patients with adult-onset nephrotic syndrome (NS) and biopsy-proven IMN. Forty-two patients were allocated to MMF + S group (MMF 1 gm twice daily + oral prednisolone 0.5 mg/kg/day; n = 21) and mPR group [methylprednisolone (1 gm intravenous) for 3 days followed by alternating monthly cycles of oral prednisolone (0.5 mg/kg/day) for the next 27 days and cyclophosphamide (2 mg/kg/day) for 6 months; n = 21]. The primary outcome measure was change in urinary protein creatinine ratio (UPCR). At 6 months, both groups demonstrated a significant increase in serum albumin levels and estimated glomerular filtration rate (eGFR) (both p-values <0.0001) as well as a decrease in 24-hour proteinuria (MMF + S group: p-value = 0.003, and mPR group: p-value <0.0001) and UPCR (both p-values <0.0001). However, the groups did not differ in any of these parameters at any of the monthly follow-up visits. Moreover, the groups did not differ significantly in terms of the composite remission rates (61.91% for MMF + S group and 71.43% for mPR group). MMF + S and mPR had comparable tolerability and effectiveness, with MMF-associated advantage of reduced steroid exposure.

Real-World Data on Tezepelumab in Patients With Severe Asthma in Germany

Tezepelumab is a novel biologic blocking thymic stromal lymphopoetin, approved for severe asthma irrespective of biomarker levels or phenotype. To characterize a real-world tezepelumab patient cohort and the efficacy among various asthma phenotypes. We performed a retrospective, multicenter study on patients with severe asthma initiating tezepelumab. Clinical response was evaluated at 3 and 6 months. We included 129 patients with an average age of 52.5 ± 13.1 years, 59.7% were female. The majority (86.0%) had increased type 2 (T2) biomarkers, 68.2% an allergic and 31.8% an eosinophilic phenotype. 23.3% of patients were biologic-naive. 22 (18.2%) patients discontinued tezepelumab therapy owing to suspected side effects or insufficient efficacy. At 6 months' follow-up, median reduction in annualized exacerbation rate was-1 [25th percentile; 75% percentile {-2.9; 0.0}], the reduction of oral corticosteroid dose among patients with long-term oral corticosteroid therapy was -5 mg [-10; 0] and the Asthma Control Test (ACT) improved by 2 [0; 5] points. A treatment response according to Biologic Asthma Response Score of 80.8% was demonstrated. There were no significant differences in treatment response between T2-high versus T2-low, early- versus adult-onset and eosinophilic versus non-eosinophilic asthma. Prior treatment with other biologics was associated with inferior treatment response. In this real-life cohort, including a large proportion of patients with history of previous biologic use and encompassing various subgroups, the majority responded to tezepelumab. Our data further suggest a steroid-sparing effect of tezepelumab.

Association of systemic lupus erythematosus standard of care immunosuppressants with glucocorticoid use and disease outcomes: a multicentre cohort study

BackgroundThis study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data.MethodsThe Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.ResultsAmong 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23–82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53–0.86], p = 0.001) and methotrexate (OR 0.68 [0.47–0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64–0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.ConclusionsThis study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

The steroid-sparing effect of JAK inhibitors across multiple patient populations.

JAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. We prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment. In all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. Chronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.

Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis.

Asthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting interleukin 5 (IL-5) and its receptor, respectively. They have been shown to be effective in steroid-sparing in patients with severe eosinophilic asthma. Our aim was to evaluate the efficacy and safety of mepolizumab and benralizumab prescribed for severe asthma in patients with EGPA under "real-world" conditions. This was a retrospective analysis of patients with EGPA and persistent asthma who received either mepolizumab 100 or 300 mg administered every 4 weeks, or benralizumab 30 mg administered every 4 weeks for the initial 3 injections and followed by an injection every 8 weeks thereafter, whilst combined with oral glucocorticoids. The follow-up every 6 ± 3 months included an assessment of clinical manifestations, pulmonary function tests and eosinophil cell count. The primary outcome was the proportion of patients at 12 months receiving a daily oral dose of prednisone or equivalent of 4 mg or less with a BVAS of 0. Twenty-six patients were included. After 12 months of treatment with mepolizumab or benralizumab, 32% of patients met the primary outcome and were receiving less than 4 mg of prednisone per day with a BVAS of 0. The median dose of prednisone was 10 mg per day at baseline, 9 mg at 6 months, and 5 mg at 12 months (p ≤ 0.01). At 12 months, 23% of patients were weaned off corticosteroids, while an increase or no change in dose was observed in 27% of patients. The median eosinophil count was significantly reduced from 365 cells/mm3 to 55 cells/mm3 at 6 months and 70 cells/mm3 at 12 months, respectively. No significant change was observed in FEV1. After 12 months of treatment, 14% of patients had had an average of 1 exacerbation of asthma, compared with 52% of patients before baseline. The tolerability profile was favorable. In this real-world study in patients with severe asthma and a history of EGPA asthma, mepolizumab and benralizumab had a significant steroid-sparing effect and reduced asthma exacerbation, but no significant effect on lung function.

Efficacy of off-the-shelf bone marrow mesenchymal stem cells for pediatric steroid-refractory acute graft-versus-host disease.

Temcell is a mesenchymal stem cell (MSC) product approved for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in Japan. However, reports regarding Temcell's efficacy in pediatric patients have been scarce, and the appropriate use of MSC therapy against pediatric SR-aGVHD also remains to be determined. We retrospectively assessed a cohort of pediatric patients treated with Temcell for SR-aGVHD following allogeneic hematopoietic transplantation. MSCs were infused intravenously at a dose of 2 × 106 cells/kg according to the manufacturer's instructions. Twelve patients received eighteen cycles of MSC therapy (median age, 10.3 [1.7-17.8] years), with four receiving additional cycles (one cycle: n = 3, three cycles: n = 1). The severity of aGVHD before MSC therapy was grade I-II in three patients and grade III-IV in nine patients (gut stage 3-4, n= 7; liver stage 3-4; n =2). The median number of immunosuppressive therapy regimens received prior to MSC administration was two (range: 1-5). The first MSC cycle displayed the best overall response rate of 83%, including six patients with a complete response (CR) and with a 49% reduction in the mean daily dose of prednisone after eight weeks. The median time to first response was 3.5 days (range: 2-15 days). Two of the four patients who were re-administered MSCs for recurrent or persistent GVHD achieved a CR. The three-year overall survival rate was 69.4%, while the three-year failure free survival (FFS) rate was 22.2%, with a median FFS of 4.9 months. There were no observable side effects of MSC therapy. MSC therapy appears to be an effective and safe treatment for pediatric SR-aGVHD, with a steroid-sparing effect and satisfactory efficacy upon re-administration. Further studies are needed to determine its appropriate combination with additional treatments and the optimal use of re-administration of MSCs.

Steroid-sparing effect of emollients in atopic dermatitis and psoriasis

The aim of the present article is to analyze the role of emollients in the topical management of atopic dermatitis and psoriasis and also to review the clinical studies available on the beneficial effect of co-therapy of emollients and topical corticosteroids. Understanding the stratum corneum's key involvement in the pathophysiology of atopic dermatitis and psoriasis has led to the development of new therapeutic approaches for treating not just inflammation but also restoring a healthy skin barrier. While topical corticosteroids are the cornerstones of treatment for atopic dermatitis and psoriasis, the potential risks of overuse (including atrophy, striae, dyspigmentation, and loss in epidermal barrier homeostasis) must be weighed against the benefits. These risks futher increase the necessity of finding non-steroidal treatments. Emollients aid the epidermal barrier function as they improve the oil and lipid levels and restore its protective function. Used regularly, emollients may reduce flare-ups and may also have a direct anti-inflammatory effect and may reduce the need to use topical corticosteroids, i.e. they have a ‘steroid sparing effect’.

Doxofylline as a steroid-sparing treatment in Mexican children with asthma

Objective The aim of this pilot study was to assess the efficacy of doxofylline as an ICS-sparing agent in the treatment of Mexican children with asthma. Methods 10-week, open-label, crossover, pilot study, we examined the steroid-sparing effect of doxofylline in Mexican children with asthma. Patients aged 6–16 years treated with inhaled corticosteroids (ICS) for at least 8 wk before enrollment were divided randomly into two groups at the baseline visit. Group A (n = 31) received doxofylline (18 mg/kg/day) plus standard-dose budesonide (D + SDB) for the first 4-week period followed by doxofylline plus reduced-dose budesonide (D + RDB) for the second 4-week period. Group B (n = 30) received D + RDB followed by D + SDB. Clinical outcomes assessed included lung function (forced expiratory volume; in 1 s, FEV1), fractional exhaled nitric oxide (FeNO), asthma control, number of exacerbations and use of rescue medication (salbutamol). Results It was shown that combined use of doxofylline and ICS may allow children with asthma to reduce their daily dose of ICS while maintaining lung function and improving asthma control (p = 0.008). There were few asthma exacerbations and only one patient required treatment with systemic corticosteroids. Rescue medication use decreased significantly in patients receiving D + SDB during the first 4-week period. Conclusions Our results suggest that doxofylline may be a steroid-sparing treatment in asthma, but longer-term, controlled studies are needed to confirm these observations.

Steroid-sparing effect of belimumab: results from a retrospective observational study of real-world data

ObjectiveComparison of oral corticosteroid (OCS) use in patients with SLE in a US rheumatology network pre- and post-belimumab initiation.MethodsThis retrospective cohort study (GSK Study 214140) used data from the Patient-Important...

Effect of belimumab in patients with systemic lupus erythematosus treated with low dose or no corticosteroids.

Systemic lupus erythematosus (SLE) responder index (SRI)-4 response has been achieved with belimumab treatment in patients with moderate disease activity in cornerstone clinical trials and following studies. However, most studies involved patients treated with a mean prednisolone-equivalent dose of approximately 10 mg/d and focused on the steroid-sparing effect of belimumab. We aimed to identify the effect of belimumab in patients with mild-to-moderate SLE who were treated with low-dose or no corticosteroids. We retrospectively reviewed the electronic medical records of patients treated with belimumab for at least 6 months between May 2021 and June 2022. The primary endpoint was SRI-4 response at 6 months. Thirty-one patients were included (13 low dose- and 18 steroid non-users). The mean age was 39.2 ± 11.4 years, and 90.3% of patients were female. The baseline Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 6.0 (4.0-9.0). The primary endpoint was achieved in 32.3% (10/31) of patients. Significant improvements in anemia, C4 levels, and SELENA-SLEDAI score were observed during treatment. Univariate analysis showed that the baseline SELENA-SLEDAI and arthritis were significantly associated with SRI-4 response at 6 months, and only the SELENA-SLEDAI remained significant (p = 0.014) in multivariate analysis. This cohort study is the first to report the efficacy of belimumab after minimizing the effect of corticosteroids. Belimumab showed efficacy in improving the SELENA-SLEDAI score, anemia, and low C4 in patients who did not receive corticosteroids or received only low doses.

Budesonide Added to Post-Transplantation Cyclophosphamide, Tacrolimus and Mycophenolate Mofetil for Prevention of Graft-Versus-Host Disease

Background: Topically active corticosteroids have been shown to effectively treat inflammatory bowel disease with a systemic steroid-sparing effect. However, previous studies have not demonstrated their efficacy in preventing graft-versus-host disease (GVHD) when combined with the standard GVHD prophylaxis regimen consisting of calcineurin inhibitors and methotrexate. We hypothesized that the addition of orally administered ileal-controlled-release budesonide to the post-transplant cyclophosphamide (PTCy)-based regimen could effectively prevent severe acute gastrointestinal GVHD. In this study, we present outcomes of the first 43 consecutively treated patients (pts) with the PTCy-tacrolimus (T), mycophenolate mofetil (M) and budesonide (B) (PTCy-TMB) as a GVHD prophylaxis regimen after allogeneic stem cell transplantation (alloSCT). Methods: Pts with hematologic malignancies received their first alloSCT at our institution between 05/2020-04/2023. Thirty one pts received conditioning with fludarabine (160 mg/m 2) + melphalan (100-140 mg/m 2) + TBI (2-4Gy) or thiotepa 5 mg/kg. Twelve pts received fludarabine (150mg/m 2) + cyclophosphamide (29mg/kg) and TBI 4Gy ± ATG (4.5 mg/kg). GVHD prophylaxis consisted of Cy (50 mg/kg on D+3 and +4), T (trough goal 6-10 ng/mL), M (15mg/kg TID) and budesonide (3 mg TID) starting on D+5 and continued until D+90 followed by a weekly taper if no acute GVHD (aGVHD) occurred. T was continued for at least 6 months followed by a taper, unless otherwise indicated. Results: The median age was 50 years (range 22-73), 39 pts had hematologic malignancies including AML (N=14), ALL (N=11) and NHL (N=8). Seven pts (16%) classified as high/very-high DRI. The median of HCT-CI was 4 (range 0-7). Donors were haploidentical (N=32), MSD (N=8), MUD (N=1), MMSD (1) and MMUD (N=1). PBSCs were used in 28 pts (65%). Thirty pts (70%) received RIC regimens. Median follow-up was 407 days (range 91-996 days). At day 100, the cumulative incidence (CI) of grade 2 aGVHD was 7.0% (95%CI 1.8-17.2), while none developed grade 3-4 aGVHD (Figure 1). One patient had severe chronic GVHD (bronchiolitis obliterans) with CI at 2 years of 3.2% (95%CI 0-14.0). The CI of any systemic steroid use at D+100 and D+180 was 30.2% (95%CI 17.4-44.1) and 44.8% (95%CI 28.9-59.5), respectively. Among the pts who received treatment for aGVHD, the median cumulative systemic steroid exposure (in prednisone equivalents) was 1,318 mg (IQR 623-3,775) at D+100 and 1,325 mg (IQR 525-1,640) at D+180, with a median treatment duration of 40 days (IQR 25-110). At 1 year, the OS, PFS, GRFS, relapse and NRM were 79.6% (95%CI 61.4-89.9), 69.8% (95%CI 51.6-82.3), 66.6% (95%CI 48.4-79.8), 15.3% (95%CI 6.2-28.2) and 14.9% (95%CI 5.3-29.1), respectively. The 1-year CI of newly diagnosed/worsening hyperglycemia and Cushing syndrome was 18.2% (95%CI 7.9-31.9) and 5.0% (95%CI 0.9-14.2), respectively. 3 pts (7%) required insulin treatment. The median absolute lymphocyte count (ALC) at day 30, 90 and 180 was 200/mcL, 300/mcL and 500/mcL, respectively, with no differences in the median ALC at D+180 among pts with and without GVHD. Median cell numbers of CD3 +, CD3 +/CD4 +, CD3 +/CD8 +, CD19 + and CD56 + at 1, 3, 6 months post-transplant were D+30 - 63/mcL, 18/mcL, 34/mcL, 1/mcL, 87/mcL, D+90 - 111/mcL, 64/mcL, 34/mcL, 9/mcL, 216/mcL and D+180 - 269/mcL , 78/mcL , 126/mcL , 7/mcL, 189/mcL, respectively. After 10/2022 pts were tested routinely for Reg3α and ST2 (baseline and retested if developed any signs/symptoms of aGVHD). Among 18 tested pts at baseline, the median number (range) of Reg3α and ST2 at baseline was 28 ng/mL (16-90) and 23,308 pg/mL (4,678-56,226), respectively. Three low-risk pts developed grade 1 aGVHD (N=2) and grade 2 aGVHD (N=1). Fourteen pts with GI sign/symptoms after transplant showed median number (range) of Reg3α and ST2 of 78 ng/mL (16-837) and 34,904 pg/mL (13,329-160,000), respectively. Only one pt with high-risk aGVHD algorithm developed grade 2 aGVHD (Figure 1). Conclusions: The addition of budesonide to PTCy-based GVHD prophylaxis regimen (PTCy-TMB) is feasible and appears to be effective in preventing severe GI aGVHD, without compromising transplant outcomes and immunologic reconstitution.

Janus kinase inhibitor for anti-transcription intermediary factor 1-γ positive cancer-associated dermatomyositis.

In this retrospective case series, off-label use of Janus kinase inhibitor rapidly and significantly ameliorated the active cutaneous disease in all five glucocorticoid-resistant patients with cancer-associated dermatomyositis who had anti-transcription intermediary factor 1-γ antibodies, showing a promising steroid-sparing effect and a generally well-tolerated safety profile beyond 1-year follow-up.