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1.
Fostamatinib for warm antibody autoimmune hemolytic anemia: Phase 3, randomized, double-blind, placebo-controlled, global study (FORWARD)
Kuter, D. J., Piatek, C., Röth, A., Siddiqui, A., Numerof, R. P., Dummer, W.
American journal of hematology. 2023
Abstract
Warm antibody autoimmune hemolytic anemia (wAIHA) is characterized by hemolysis and symptomatic anemia with no approved treatment options. Fostamatinib is an oral spleen tyrosine kinase inhibitor approved in the US and Europe for treatment of adults with chronic immune thrombocytopenia. In this phase 3 study, patients with an insufficient response to ≥1 prior wAIHA treatment were randomized to fostamatinib or placebo. The primary endpoint was the proportion of patients to achieve a durable hemoglobin (Hgb) response (Hgb ≥10 g/dL and increase from baseline of ≥2 g/dL on 3 consecutive visits) during the 24-week treatment period. Ninety patients were randomized, 45 to each arm. Of the fostamatinib-treated patients, 35.6% achieved a durable Hgb response versus 26.7% on placebo (p = .398). A post hoc analysis revealed a large placebo response in Eastern European patients. Significantly more patients on fostamatinib from North America, Australia and Western Europe exhibited a durable Hgb response compared to placebo (36% vs. 10.7%, p = .030). After censoring for Hgb values impacted by steroid rescue received during screening and excluding 2 placebo patients found to likely not have wAIHA, a reanalysis demonstrated a difference in durable Hgb response between fostamatinib and placebo (15/45 [33.3%] vs. 6/43 [14.0%], p = .0395). At least 1 AE was reported in 42 (93.3%) and 40 (88.9%) patients receiving fostamatinib and placebo, respectively. The most common AEs in the fostamatinib group were diarrhea (26.7%), hypertension (24.4%), and fatigue (15.6%). In this study, fostamatinib demonstrated a clinically meaningful benefit for patients in Western regions, and no new safety signals were identified.
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2.
Concomitant Immunosuppressive Therapy Use in Eculizumab-Treated Adults With Generalized Myasthenia Gravis During the REGAIN Open-Label Extension Study
Nowak RJ, Muppidi S, Beydoun SR, O'Brien FL, Yountz M, Howard JF Jr
Frontiers in neurology. 2020;11:556104
Abstract
Introduction: Chronic, broad-spectrum immunosuppressive therapy (IST) can be associated with side effects in many people with generalized myasthenia gravis (gMG), and treatment guidelines recommend that the IST dose be tapered once patients achieve a stable treatment response. We therefore examined IST use in eculizumab-treated patients with refractory gMG. Methods: The REGAIN open-label extension (OLE) enrolled 117 adults with refractory anti-acetylcholine receptor antibody-positive gMG who had completed the 6-month, randomized, double-blind, placebo-controlled REGAIN study of eculizumab. Eligible patients had received ≥2 ISTs for ≥1 year or ≥1 IST with intravenous immunoglobulin or plasma exchange ≥4 times in 1 year, without symptom control. During REGAIN, changes in concomitant MG therapies were not permitted; during the OLE, they were permitted at the investigators' discretion. Participants received eculizumab 1,200 mg every 2 weeks for up to 4 years; concomitant prednisone and related corticosteroids (PRED), azathioprine (AZA), and mycophenolate mofetil (MMF) use was recorded. Changes in MG Activities of Daily Living and Quantitative MG total scores, MG exacerbations, and adverse events were also recorded. Results: At last OLE assessment, 88.0% (103/117) of participants were using ≥1 IST vs. 98.3% (115/117) at OLE baseline. During the OLE, 76.9% (90/117) of patients experienced a total of 719 IST changes. Almost half of participants [48.7% (57/117)] stopped or decreased ≥1 IST owing to MG symptom improvement, representing 38.9% (280/719) of all changes. In patients who decreased and/or stopped ≥1 IST, mean daily doses of PRED, AZA, and MMF decreased between OLE baseline and last assessment by 60.8% [standard deviation (SD), 28.07; P < 0.0001], 89.1% (SD, 25.77; P < 0.0001), and 56.0% (SD, 32.99; P < 0.0001), respectively. Improved clinical outcomes were observed with eculizumab regardless of IST changes during the OLE, and eculizumab's safety profile was similar in patients who used PRED, AZA, and MMF. Conclusions: Use of ISTs by patients with previously refractory gMG decreased during eculizumab treatment in the REGAIN OLE. Clinical improvements with eculizumab were maintained by patients in all groups, including those who decreased and/or stopped concomitant ISTs. Trial registration: www.clinicaltrials.gov: NCT01997229, NCT02301624.
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3.
Mucous membrane grafting (fibrin glue vs. suture) for lid margin pathologies in Stevens-Johnson syndrome: randomized comparative study
Pushker N, Gorimanipalli B, Sharma N, Kashyap S, Bajaj MS
Eye (London, England). 2020
Abstract
OBJECTIVE To compare fibrin glue (with three cardinal sutures) (FG) and polygalactin suture (PS) for mucous membrane grafting (MMG) in terms of graft apposition and recurrence of lid margin keratinization (LMK) and metaplastic lashes (ML) in patients with Stevens-Johnson syndrome (SJS). DESIGN Prospective randomized comparative interventional study. METHODS Twenty patients diagnosed with SJS and lid margin abnormalities including LMK with or without ML were randomized to undergo either fibrin glue (FG)-assisted MMG (n = 10) or continuous 8-0 polygalactin suture (PS)-assisted MMG (n = 10). They were evaluated preoperatively and during follow-up at 1 week and 1, 2, 3, and 6 months. The parameters assessed were best-corrected visual acuity (BCVA), tear break-up time (TBUT), Schirmer-1 test, corneal and conjunctival complications, graft apposition and width (GW), LMK, ML, impression cytology, and operative time. The primary outcome measures are incidence of graft displacement and recurrence of LMK and ML. RESULTS None of the eyelids in FG group (0/40) and 1 eyelid in PS group (1/40) had graft displacement. Recurrence of LMK occurred in 7.5% of eyelids (3/40) in both the study groups. Recurrence of ML occurred in 2.5% (1/40) in FG group and 5% (2/40) in PS group. The mean operative time for MMG in FG group was 39.5 ± 2.40 min and in PS group was 56 ± 1.63 min (p = 0.001). CONCLUSIONS As graft apposition with suture involves significantly longer intraoperative time, if cost is not a limiting factor then fibrin glue is a viable option for the MMG for lid margin pathologies.
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4.
Reduced insulin need in patients with type 2 diabetes mellitus (T2DM) with iron deficiency anemia treated with sucrosomial iron vs intravenous sodium ferrigluconate. Multicentric prospective study
Giordano G, Parente A, Gigli R, Magri M, Berardi G, Carabellese B, D’Amico F, Luciano L, Fratangelo R, Niro G, et al
Haematologica. 2016;101((s1)):848.. pb2134.
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5.
Influence of recombinant human erythropoietin (rHuEPO) on plasma levels of selected hormones in females with rheumatoid arthritis Polish
Dyjas R, Buanowski M, Ficek R, Witkowicz J, Chudek J, Wiecek A
Polskie Archiwum Medycyny Wewnetrznej. 2005;114((2):):731-7.
Abstract
During recent years, it was shown, that treatment with recombinant human erythropoietin (rHuEPO) stimulates erythropoiesis in patients both with renal and nonrenal anaemia. Additionally in patients with chronic renal failure treated with rHuEPO a significant, however only transient, influence on function of endocrine glands was also found. The present study aimed to asses for the first time the influence of rHuEPO on function of endocrine organs in anaemic patients with rheumatoid arthritis and normal renal function. Twenty two woman with rheumatoid arthritis and concomitant anaemia (Ht < or = 30%) were enrolled into the study. In 13 of them rHuEPO was used during 4 months (5000 IU 2 times per week s. c. ). The rest 9 woman with similar degree of anaemia did not receive rHuEPO therapy. In woman of both groups intensive clinical and biochemical monitoring during 4 months period was performed. Blood samples were withdrawn before and after 4 months of rHuEPO therapy or clinical observation only. In these blood samples plasma concentrations of somatotropin (HGH), insulin (IRI), aldosterone (ALD), atrial natriuretic peptide (ANP), 25-hydroxycholecalciferol (25OHD3), intact parathyroid hormone (iPTH) and plasma renin activity (PRA) were estimated. After 4 months of rHuEPO therapy significant increase of plasma IRI, ANP concentrations and significant decrease of PRA and plasma ALD, HGH concentrations were found. Therapy with rHuEPO does not influence significantly plasma iPTH and 25OHD3 concentration. During 4 months of clinical observation in patients not treated with rHuEPO, plasma concentrations of HGH, IRI, ALD, ANP, 25OHD3, iPTH and plasma renin activity (PRA) did not change significantly. Results obtained in this study suggest, that rHuEPO therapy does influence the function of endocrine organs also in patients with rheumatoid arthritis with normal renal function.
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6.
No therapeutic effect of plasmin antagonist tranexamic acid in rheumatoid arthritis. A double-blind placebo-controlled pilot study
van der Laan WH, Ronday HK, TeKoppele JM, Breedveld FC, Huizinga TW, Verheijen JH
Clinical & Experimental Rheumatology. 2003;21((3)):359-62.
Abstract
OBJECTIVE In the present study, the effects of plasmin antagonist tranexamic acid (TEA) on urinary pyridinoline excretion rates were investigated in rheumatoid arthritis (RA) patients. METHODS The study was set up as a double-blind placebo-controlled pilot study. Ten patients received tranexamic acid and 9 received placebo for 12 weeks. Urinary excretion rates of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) were used as molecular markers of articular cartilage and bone degradation. In addition, clinical parameters of disease activity were assessed and CRP levels were measured. RESULTS Treatment with TEA did not reduce pyridinoline excretion, nor was any effect observed on clinical parameters of disease activity or on CRP levels. CONCLUSION The results of the present pilot study show no beneficial effect of TEA as adjuvant therapy in RA patients with respect to joint destruction or disease activity. RN 0 (Amino Acids). 63800-01-1 (pyridinoline). 6T84R30KC1 (Tranexamic Acid). EC 3-4-21-7 (Fibrinolysin).
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7.
Recombinant human erythropoietin improves health-related quality of life in patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease activity measures
Peeters HR, Jongen-Lavrencic M, Bakker CH, Vreugdenhil G, Breedveld FC, Swaak AJ
Rheumatology International. 1999;18((5-6):):201-6.
Abstract
Treatment with recombinant human erythropoietin (r-hu-Epo) in patients with rheumatoid arthritis (RA) and anaemia of chronic disease (ACD) resulted in improvement of both anaemia and disease activity. Utilities represent a generic and comprehensive quality of life measure, capable of integrating domain-specific information into one overall value which a patient assigns to his state of health. Therefore, the effect of r-hu-Epo on quality of life was studied by measuring utilities, derived from the rating scale and standard gamble, in a 52-week placebo-controlled randomised double-blind study with r-hu-Epo in 70 patients with active RA and ACD. Furthermore, the relation between anaemia as assessed by haemoglobin levels (Hb), disease activity as assessed with the Disease Activity Score (DAS), and utilities was investigated. Compared to the placebo group, significant improvement of Hb (P < 0.001), DAS (P = 0.01) and rating scale utilities (P = 0.002), but not of standard gamble utilities, was observed in the Epo group. Rating scale utilities correlated strongly with DAS (r = -0.47, P < 0.01), Hb (r = 0.37, P < 0.01) and changes in both DAS (r = -0.74, P < 0.01) and Hb (r = 0.44, P < 0.01). Both DAS and Hb contributed significantly to the variance in rating scale utilities (21% and 3% respectively) and to changes in rating scale utilities (43% and 3% respectively). Standard gamble utilities correlated less well with clinical disease variables than rating scale utilities did. These results indicate, that r-hu-Epo improves utility-derived health-related quality of life, most probably by improving both disease activity and anaemia. Utilities, particularly rating scale utilities, correlated well with conventional disease activity variables and proved sensitive to change. Utilities may be a useful tool for investigating quality of life in RA-patients.
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8.
Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis
Nordstrom D, Lindroth Y, Marsal L, Hafstrom I, Henrich C, Rantapaa-Dahlqvist S, Engstrom-Laurent A, Fyhrquist F, Friman C
Rheumatology International. 1997;17((2):):67-73.
Abstract
Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb < 100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb > or = 120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12 +/- 1.2 g/l vs 4 +/- 0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P < 0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18 +/- 1.1 g/l vs 7 +/- 1.1 g/l, P < 0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenuous efforts should have been made to control the disease itself.
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9.
Intravenous iron and erythropoietin for anemia associated with Crohn disease. A randomized, controlled trial
Gasche C, Dejaco C, Waldhoer T, Tillinger W, Reinisch W, Fueger GF, Gangl A, Lochs H
Annals of Internal Medicine. 1997;126((10):):782-7.
Abstract
BACKGROUND Anemia often complicates Crohn disease and affects quality of life. OBJECTIVE To evaluate the efficacy of intravenous iron alone and in combination with erythropoietin for the treatment of anemia associated with Crohn disease. DESIGN Double-blind, randomized, placebo-controlled trial with a subsequent open-label phase. SETTING University-based gastroenterology outpatient clinic. PATIENTS 40 patients with Crohn disease and a hemoglobin concentration of 10.5 g/dL or less. INTERVENTION All patients received intravenous iron saccharate for 16 weeks. During the blinded phase of the trial, they received either erythropoietin or placebo. During the open phase, the erythropoietin dose was increased in non-responders who had received erythropoietin and erythropoietin therapy was initiated in nonresponders who had received placebo. MEASUREMENTS Response was defined as an increase in hemoglobin concentration of 2 g/dL or more. RESULTS 15 of 20 patients in the placebo group (75% [95% CI, 51% to 91%]) and 18 of 19 patients in the erythropoietin group (95% [CI, 74% to 100%]) responded to intravenous iron (P = 0.20). The erythropoietin group had a higher cumulative response rate (P = 0.036) and a more pronounced mean increase in hemoglobin concentration (4.9 g/dL in the erythropoietin group compared with 3.3 g/dL in the placebo group, a difference of 1.6 g/dL [CI, 0.6 g/dL to 2.5 g/dL]; P = 0.004). In the open phase, all 6 previous nonresponders had a response. Hematologic response was associated with improved quality of life (P = 0.03). CONCLUSIONS Most patients who have anemia associated with Crohn disease respond to intravenous iron alone. Erythropoietin has additional effects on hemoglobin concentrations.
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10.
Study of erythropoietin in treatment of anaemia in patients with rheumatoid arthritis
Murphy EA, Bell AL, Wojtulewski J, Brzeski M, Madhok R, Capell HA
Bmj. 1994;309((6965):):1337-8.