ABSTRACT
INTRODUCTION: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are not well understood. We aimed to describe serious infectious complications and their potential risk factors. METHODS: Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry. Episodes of serious infections were described, and their risk factors were analysed using multivariable Cox proportional hazards models. RESULTS: Seventy-four patients with 133 serious infections were included. The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Microbiological confirmation was obtained in 76%: 52% bacterial, 30% viral, 15% fungal and 3% mycobacterial. Among the pulmonary infections, the main pathogens were SARS-CoV-2 (28%), Legionella pneumophila (21%) and Pneumocystis jirovecii (19%). Sixteen per cent of severe infections occurred without any immunosuppressive treatment and with a daily glucocorticoid dose ≤10 mg. In multivariate analysis, age >75 years (HR (95% CI) 1.81 (1.02 to 3.24)), p.Met41Val mutation (2.29 (1.10 to 5.10)) and arthralgia (2.14 (1.18 to 3.52)) were associated with the risk of serious infections. JAK inhibitors were most associated with serious infections (3.84 (1.89 to 7.81)) compared with biologics and azacitidine. After a median follow-up of 4.4 (2.5-7.7) years, 27 (36%) patients died, including 15 (56%) due to serious infections. CONCLUSION: VEXAS syndrome is associated with a high incidence of serious infections, especially in older patients carrying the p.Met41Val mutation and treated with JAK inhibitors. The high frequency of atypical infections, especially in patients without treatment, may indicate an intrinsic immunodeficiency.
Subject(s)
Bacteriophages , Janus Kinase Inhibitors , Myelodysplastic Syndromes , Skin Diseases, Genetic , Aged , Humans , Arthralgia , Azacitidine , Mutation , Retrospective StudiesABSTRACT
OBJECTIVES: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies. METHODS: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy. Complete response (CR) was defined by a clinical remission, C-reactive protein (CRP) ≤10 mg/L and a ≤10 mg/day of prednisone-equivalent therapy, and partial response (PR) was defined by a clinical remission and a 50% reduction in CRP levels and glucocorticoid dose. RESULTS: 110 patients (median age 71 (68-79) years) who received 194 targeted therapies were included: 78 (40%) received Janus kinase (JAK) inhibitors (JAKi), 51 (26%) interleukin (IL)-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) tumour necrosis factor (TNFα) blockers and 12 (6%) other targeted therapies. At 3 months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNFα blockers or other targeted therapies. At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors. Survival without treatment discontinuation was significantly longer with JAKi than with the other targeted therapies. Among patients who discontinued treatment, causes were primary failure, secondary failure, serious adverse event or death in 43%, 14%, 19% and 19%, respectively, with JAKi and 46%, 11%, 31% and 9%, respectively, with IL-6 inhibitors. CONCLUSIONS: This study shows the benefit of JAKi and IL-6 inhibitors, whereas other therapies have lower efficacy. These results need to be confirmed in prospective trials.
ABSTRACT
OBJECTIVE: To identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy. METHODS: We conducted a nationwide retrospective case-control study of GPA with induction failure between 2006 and 2021. Each patient with induction failure was randomly paired to three controls matched for age, sex and induction treatment. RESULTS: We included 51 patients with GPA and induction failure (29 men and 22 women). At induction therapy, median age was 49 years. Twenty-seven patients received intravenous cyclophosphamide (ivCYC) and 24 rituximab (RTX) as induction therapy. Patients with ivCYC induction failure more frequently had PR3-ANCA (93% vs 70%, P = 0.02), relapsing disease (41% vs 7%, P < 0.001) and orbital mass (15% vs 0%, P < 0.01) compared with controls. Patients with disease progression despite RTX induction therapy more frequently had renal involvement (67% vs 25%, P = 0.02) with renal failure (serum creatinine >100 µmol/l in 42% vs 8%, P = 0.02) compared with controls. After salvage therapy, remission was achieved at 6 months in 35 (69%) patients. The most frequent salvage therapy was switching from ivCYC to RTX (or vice versa), showing an efficacy in 21/29 (72%). Remission was achieved in nine (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in four (100%) who received ivCYC (with or without immunomodulatory therapy), but only in three (50%) after adding immunomodulatory therapy alone. CONCLUSION: In patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Granulomatosis with Polyangiitis , Male , Humans , Female , Middle Aged , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/drug therapy , Retrospective Studies , Case-Control Studies , Treatment Outcome , Rituximab/therapeutic use , Cyclophosphamide/therapeutic use , Risk Factors , Remission InductionABSTRACT
Azacitidine can be effective in myelodysplastic syndromes (MDS) associated with inflammatory/autoimmune diseases. Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) is a new monogenic autoinflammatory syndrome caused by somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutation, often associated with MDS, whose treatment is difficult and not yet codified. Based on a French nationwide registry of 116 patients with VEXAS, we report the efficacy and safety of azacitidine treatment in 11 patients with VEXAS with MDS. Clinical response of VEXAS to azacitidine was achieved in five patients (46%), during 6, 8+, 12, 21, 27+ months respectively, suggesting that azacitidine can be effective in selected patients with VEXAS and associated MDS.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Genes, X-Linked/genetics , Genetic Diseases, X-Linked/genetics , Myelodysplastic Syndromes/drug therapy , Skin Diseases, Genetic/drug therapy , Aged , Antimetabolites, Antineoplastic/pharmacology , Azacitidine/pharmacology , Female , France , Humans , Male , Middle Aged , RegistriesABSTRACT
BACKGROUND: Cardiac sarcoidosis (CS) is a life-threatening condition in which clear recommendations are lacking. We aimed to systematically review the literature on cardiac sarcoidosis treated by corticosteroids and/or immunosuppressive agents in order to update the management of CS. METHODS: Using PubMed, Embase and Cochrane Library databases, we found original articles on corticosteroid and standard immunosuppressive therapies for CS that provided at least a fair Scottish Intercollegiate Guidelines Network (SIGN) overall assessment of quality and we analysed the relapse rate, major cardiac adverse events (MACEs) and adverse events. We based our methods on the PRISMA statement and checklist. RESULTS: We retrieved 21 studies. Mean quality provided by SIGN assessment was 6.8 out of 14 (range 5-9). Corticosteroids appeared to have a positive impact on left ventricular function, atrioventricular block and ventricular arrhythmias. For corticosteroids alone, nine studies (45%, n=351) provided data on relapses, representing an incidence of 34% (n=119). Three studies (14%, n=73) provided data on MACEs (n=33), representing 45% of MACEs in patients treated by corticosteroid alone. Nine studies provided data on adjunctive immunosuppressive therapy, of which four studies (n=78) provided data on CS relapse, representing an incidence of 33% (n=26). Limitations consisted of no randomised control trial retrieved and unclear data on MACEs in patients treated by combined immunosuppressive agents and corticosteroids. CONCLUSION: Corticosteroids should be started early after diagnosis but the exact scheme is still unclear. Studies concerning adjunctive conventional immunosuppressive therapies are lacking and benefits of adjunctive immunosuppressive therapies are unclear. Homogenous data on CS long-term outcomes under corticosteroids, immunosuppressive therapies and other adjunctive therapies are lacking.
Subject(s)
Adrenal Cortex Hormones , Sarcoidosis , Adrenal Cortex Hormones/therapeutic use , Humans , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Recurrence , Sarcoidosis/diagnosis , Sarcoidosis/drug therapyABSTRACT
OBJECTIVES: To describe the characteristics, treatment and outcome of patients with immune thrombocytopenia with clinical significance (ITPCS) associated with SLE. METHODS: This retrospective multicentre study included SLE patients who experienced ≥1 ITPCS (defined as ITP with attributable bleeding disorders and/or a platelet count <30×109/l). Other causes of secondary thrombocytopenia were excluded. Major bleeding event (MBG) was defined as Khellaf score >8 and/or WHO score >2. RESULTS: A total of 90 patients were included, the median (range) follow-up duration was 80 (6-446) months. ITP was diagnosed before SLE in 25 patients. They presented a high rate of autoimmune haemolytic anaemia (15%), antiphospholipid antibody (62%) and antiphospholipid syndrome (19%). The 25 (28%) patients who experienced MBG had significantly more bleedings at ITP diagnosis and higher bleeding scores, and serositis and thrombosis during follow-up. They required significantly more treatment lines, transfusions and hospitalizations. The 11 (12%) patients who experienced no bleeding event presented a significantly more restricted SLE phenotype (cutaneous and/or articular). Patients received a mean (range) of 4.2 (1-11) treatment lines. Corticosteroids and HCQ allowed ITPCS overall response in one-third of patients. The median relapse-free survival of rituximab (n = 34), AZA (n = 19), MMF (n = 8), thrombopoietin-receptor agonists (n = 16) and splenectomy (n = 19) were 53, 31.5, 61, 24.5 and 78 months, respectively. Four patients experienced thrombotic events after splenectomy and one occurred under thrombopoietin-receptor agonist treatment. CONCLUSION: SLE-ITCS patients displayed a high rate of haematological abnormalities and MBG patients exhibited higher morbidity. Management of thrombocytopenia was highly heterogeneous and many options seem viable.
Subject(s)
Lupus Erythematosus, Systemic , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/complications , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Purpura, Thrombocytopenic, Idiopathic/therapy , Receptors, Thrombopoietin/agonists , Retrospective Studies , Thrombocytopenia/drug therapy , Thrombosis/drug therapyABSTRACT
PURPOSE: Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. METHODS: We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). RESULTS: Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. CONCLUSION: HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. CLINICAL IMPLICATIONS: HCT is a definitive cure for DADA2 with > 95% survival.
Subject(s)
Agammaglobulinemia/therapy , Bone Marrow Failure Disorders/therapy , Hematopoietic Stem Cell Transplantation , Severe Combined Immunodeficiency/therapy , Adenosine Deaminase/deficiency , Adolescent , Adult , Agammaglobulinemia/enzymology , Agammaglobulinemia/genetics , Agammaglobulinemia/mortality , Bone Marrow Failure Disorders/enzymology , Bone Marrow Failure Disorders/genetics , Bone Marrow Failure Disorders/mortality , Child , Child, Preschool , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Intercellular Signaling Peptides and Proteins/deficiency , Kaplan-Meier Estimate , Male , Retrospective Studies , Severe Combined Immunodeficiency/enzymology , Severe Combined Immunodeficiency/genetics , Severe Combined Immunodeficiency/mortality , Treatment Outcome , Young AdultABSTRACT
We provide the first description of a series of 9 severe gynecological infections (mastitis and pelvic cellulitis) occurring in the French national cohort of women with STAT3 deficiency. Each episode had unique features in terms of clinical presentation, microbial documentation, location, treatment duration, and related persistent esthetic damage.
Subject(s)
Mastitis/genetics , Parametritis/genetics , STAT3 Transcription Factor , Cohort Studies , Female , Humans , Mutation , STAT3 Transcription Factor/deficiency , STAT3 Transcription Factor/genetics , Young AdultSubject(s)
Janus Kinase Inhibitors , Myelodysplastic Syndromes , Skin Diseases, Genetic , Janus Kinase Inhibitors/pharmacology , Myelodysplastic Syndromes/drug therapy , Nitriles , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyrimidines , Retrospective Studies , Skin Diseases, Genetic/drug therapyABSTRACT
Rituximab is a second-line option in adults with immune thrombocytopenia (ITP), but the estimated 5-year response rate, only based on pooled retrospective data, is about 20%, and no studies have focused on long-term safety. We conducted a prospective multicenter registry of 248 adults with ITP treated with rituximab with 5 years of follow-up to assess its long-term safety and efficacy. The median follow-up was 68.4 [53.7-78.5] months. The incidence of severe infections was only 2/100 patient-years. Profound hypogammaglobulinemia (<5 g/L) developed in five patients at 15 to 31 months after the last rituximab infusion. In total, 25 patients died at a median age of 80 [69.5-83.9] years, corresponding to a mortality rate of 2.3/100 patient-years. Only three deaths related to infection that occurred 12 to 14 months after rituximab infusions could be due in part to rituximab. At 60 months of follow-up, 73 (29.4%) patients had a sustained response. On univariate and multivariate analysis, the only factor significantly associated with sustained response was a previous transient response to corticosteroids (P = .022). Overall, 24 patients with an initial response and then relapse received retreatment with rituximab, which gave a response in 92%, with a higher duration of response in 54%. As a result of its safety profile and its sustained response rate, rituximab remains an important option in the current therapeutic armamentarium for adult ITP. Retreatment could be an effective and safe option.
Subject(s)
Purpura, Thrombocytopenic, Idiopathic/drug therapy , Rituximab/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Adult , Agammaglobulinemia/chemically induced , Agammaglobulinemia/epidemiology , Aged , Aged, 80 and over , Autoimmune Diseases/epidemiology , Autoimmune Diseases/etiology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cause of Death , Disease-Free Survival , Drug Eruptions/epidemiology , Drug Eruptions/etiology , Drug Substitution , Female , Follow-Up Studies , France/epidemiology , Humans , Infections/epidemiology , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/etiology , Neoplasms/immunology , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Outcome , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/mortality , Registries , Rituximab/adverse effects , Serum Sickness/chemically induced , Serum Sickness/epidemiologyABSTRACT
BACKGROUND: Immunohistochemistry and Periodic acid-Schiff (PAS) staining have been routinely used for the diagnosis of Whipple's disease (WD). However, these methods present limitations. As a result, the last years, Fluorescence in situ hybridization (FISH) has been increasingly used as a complementary tool for the diagnosis of WD from various tissue samples. CASE REPORT: In this study, we visualized, by FISH, Tropheryma whipplei within macrophages of a lymph node from a patient with WD. Moreover, we report in this study a patient with a pulmonary biopsy compatible with WD by PAS, immunostaining and FISH, although the specific molecular assays for T. whipplei were negative. Sequencing analysis of the 16S rDNA revealed a T. whipplei-related species with unknown classification. CONCLUSION: FISH can be a valuable method for the detection of Tropheryma species in formalin-fixed paraffin-embedded tissues. FISH cannot replace the other already approved diagnostic techniques for WD, it can be used as a complementary tool and can provide supplementary information in a relatively short time.
Subject(s)
In Situ Hybridization, Fluorescence/methods , Tropheryma/isolation & purification , Whipple Disease/diagnosis , Adult , Aged , Belgium , Biopsy , Female , France , Humans , Lymph Nodes/pathology , Macrophages/pathology , Tropheryma/classification , Whipple Disease/microbiologyABSTRACT
BACKGROUND: An increased risk of thrombosis has been reported in immune thrombocytopenic purpura (ITP), but the characteristics, risk factors of occurrence, recurrence and management of venous thromboembolic events (VTE) have been poorly investigated. AIMS: To describe VTE and ITP characteristics, distribution of VTE risk factors and their impact on VTE features and recurrence. METHODS: A retrospective study of patients with ITP and VTE registered in databases of three reference French centres of ITP. RESULTS: Among 49 patients, 66 VTE were recorded. The platelet count at the time of the first VTE was <100 × 109 /L for 28/43 (65%) patients. In total, 19/48 (40%) patients had at least one positive antiphospholipid test result. For the 10 VTE occurring in eight patients with platelet count <50 × 109 /L, ITP treatment was efficient in 7. One haemorrhagic complication associated with anticoagulant (AC) therapy was recorded. For 31/49 (63%) patients, long-term AC therapy could have been discussed after the first VTE, but only 13 received it. A second VTE occurred in 13 (27%) patients. The risk of recurrence was increased in patients with unprovoked VTE before ITP diagnosis or active cancer. CONCLUSION: VTE in ITP mainly occurred in the presence of multiple risk factors of TE. A low platelet count does not protect against VTE. Management with AC therapy despite persistently low platelet count seems possible. Risk of VTE recurrence is high, particularly with a history of unprovoked VTE or active cancer. In this setting, indefinite AC therapy could be discussed.
Subject(s)
Anticoagulants/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/complications , Venous Thromboembolism/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Databases, Factual , Female , France , Hemorrhage/chemically induced , Humans , Male , Middle Aged , Platelet Count , Recurrence , Retrospective Studies , Risk Factors , Venous Thromboembolism/drug therapy , Young AdultABSTRACT
Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to splenectomy and the requirement for long-term treatment to reduce the risk of significant bleeding events. In this multicenter study, we included 37 patients with multirefractory ITP, defined as no response to splenectomy, rituximab, romiplostim, and eltrombopag. As compared with a historical cohort of 183 ITP patients, matched on the calendar year of ITP diagnosis with a 5:1 ratio, patients with multirefractory ITP were more likely to have secondary ITP (odds ratio [OR], 4.84; 95% confidence interval [CI], 1.31-17.86; P = .018) and monoclonal gammopathy of undetermined significance (OR, 5.94; 95% CI, 1.08-32.48; P = .04). The median duration of ITP before being recognized as multirefractory was 78 months (range, 6-450). The patients showed failure of a median of 10.5 prior treatment lines for ITP (range, 6-15). At the end of follow-up (median, 84 months; range, 12-455), only 1/14 patients achieved response with immunosuppressant therapy alone. By contrast, 7/10 patients achieved response with a combination of immunosuppressant therapy and thrombopoietin-receptor agonists that lasted for a median of 15 months (range, 6-32). Throughout the course of ITP, 5/37 patients died, 3 with ITP (bleeding, n = 2; sepsis n = 1); 15 (40%) had at least 1 bacterial infection and 9 (24%) at least 1 episode of thrombosis. In conclusion, multirefractory ITP was associated with high morbidity and mortality. Combining an immunosuppressant therapy with thrombopoietin-receptor agonists may be a good strategy for management for these patients with severe disease.
Subject(s)
Antineoplastic Agents/therapeutic use , Drug Resistance , Purpura, Thrombocytopenic, Idiopathic/therapy , Receptors, Fc/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Rituximab/therapeutic use , Splenectomy/adverse effects , Thrombopoietin/therapeutic use , Adolescent , Adult , Aged , Case-Control Studies , Child , Chronic Disease , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Young AdultABSTRACT
INTRODUCTION: Treatment of non-IgM type I cryoglobulinaemic vasculitis (CV) is challenging. Corticosteroids are first-line therapy, but relapses are frequent leading to therapeutic escalation. Bortezomib is a proteasome inhibitor with rapid effect on monoclonal component. However, its use in non-IgM type I CV has been barely reported. OBJECTIVE: To assess the efficacy of bortezomib in non-IgM type I CV. METHOD: Single-centre case series of four patients with non-IgM type I CV treated with bortezomib monotherapy. RESULTS: Two men and two women, 60-84 years old, received bortezomib monotherapy. Monoclonal component was IgG-λ (n = 2), IgA-λ and IgG-κ. Clinical features were necrotic rash (n = 3), synovitis (n = 3) and sensitive neuropathy (n = 2). CV was refractory to corticosteroids (n = 4), cyclophosphamide (n = 3) and rituximab (n = 2). Three patients experienced dramatic clinical improvement with undetectable cryoglobulin after three cycles (bortezomib 1.3 mg/m2 weekly). Each patient relapsed 4-18 months after treatment discontinuation. Bortezomib was unsuccessful after four cycles in one patient. Bortezomib toxicity included one pneumonia and 1 case of worsening neuropathic pain. CONCLUSION: Bortezomib in monotherapy should be considered as a valuable option in refractory non-IgM type I CV because of its swift efficacy and acceptable tolerance profile.
ABSTRACT
This Phase 3 multicentre randomized double-blind and placebo-controlled trial aimed to compare the efficacy and safety of rituximab (RTX) to placebo for treating newly diagnosed warm autoimmune hemolytic anemia (wAIHA) in adults receiving prednisone. Adults with a confirmed diagnosis of wAIHA who previously received corticosteroids for less than 6 weeks could be included. At inclusion, all patients received prednisone at a daily dose of 1 mg/kg for 2 weeks, and then tapered according to a pre-defined recommended reduction scheme. Besides prednisone, eligible patients received 2 infusions of RTX or placebo at a fixed dose of 1,000 mg 2-week apart. The primary endpoint was overall response rate (complete response [CR] + partial response [PR]) in an intent-to-treat (ITT) analysis at 1 year. A total of 32 patients (17 females [53%], mean age at inclusion 71 ± 16 years) were enrolled and randomized. In all, 27 patients were followed for at least 1 year and their data were evaluable for response. With an ITT analysis, the overall response rate at 1 year was 75% [95%CI: 47.6-92.7] with 11 CR and 1 PR with RTX versus 31% [11.0-58.7] (5 CR) with placebo (P = 0.032). At 2 years, 10/16 patients with RTX versus 3/16 with placebo still showed CR (P = 0.011). Overall, eight severe infections occurred during follow-up, six with placebo and two with RTX (P = 0.39). At 2 years, six patients with placebo had died, but none with RTX (P = 0.017). Compared to placebo, RTX combined with prednisone may be effective and safe for treating newly-diagnosed wAIHA in adults. Am. J. Hematol. 92:23-27, 2017. © 2016 Wiley Periodicals, Inc.
Subject(s)
Anemia, Hemolytic, Autoimmune/drug therapy , Immunologic Factors/therapeutic use , Prednisolone/therapeutic use , Rituximab/therapeutic use , Aged , Anemia, Hemolytic, Autoimmune/mortality , Disease-Free Survival , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Immunologic Factors/administration & dosage , Male , Prednisolone/administration & dosage , Prospective Studies , Rituximab/administration & dosage , Treatment OutcomeSubject(s)
DNA/genetics , Hereditary Autoinflammatory Diseases/genetics , Mutation , Ubiquitin-Activating Enzymes/genetics , Aged , DNA Mutational Analysis , Hereditary Autoinflammatory Diseases/diagnosis , Hereditary Autoinflammatory Diseases/metabolism , Humans , Male , Ubiquitin-Activating Enzymes/metabolismABSTRACT
We conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of sustained response. In total, 173 patients received 4 infusions of 375 mg/m(2) and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physician's preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count ≥30 × 10(9)/L and ≥2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295.