Sustained improvements in patient-reported outcomes after long-term sutimlimab in patients with cold agglutinin disease: results from the CADENZA study open-label extension.

Background: Cold agglutinin disease (CAD) is a rare subtype of autoimmune haemolytic anaemia characterised by classical complement pathway-mediated haemolysis, fatigue, and poor quality of life (QoL). Sutimlimab, a C1s inhibitor, rapidly halted haemolysis, and improved patient-reported outcomes (PROs) in patients with CAD in two phase 3 trials (CARDINAL and CADENZA). Here we report PROs from the CADENZA open-label extension (Part B). Methods: The first patient was enrolled in CADENZA (NCT03347422) in March 2018 (Part A) and the last patient completed the study in December 2021 (Part B). All patients who completed the 26-week Part A were eligible to receive biweekly doses of sutimlimab in Part B for up to 1 year after the last patient completed Part A. PROs were assessed throughout Part B, until the last on-treatment visit with available assessment (LV), and after a 9-week washout. Findings: In total, 32/39 patients completed Part B; median Part B treatment duration: 99 weeks. Patients switching from placebo to sutimlimab in Part B experienced rapid improvement in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score and other PROs. Sustained, clinically important improvements in FACIT-Fatigue were observed throughout Part B in patients who switched to sutimlimab and those continuing sutimlimab treatment (combined-group mean [SE] change from baseline at LV: 8.8 [2.1]). Similarly, the combined-group mean [SE] change for 12-Item Short Form Health Survey physical (4.9 [1.7]) and mental (4.0 [1.8]) component scores exceeded clinically important changes from baseline at LV. EuroQol visual analogue scale showed consistent and sustained increases from baseline with sutimlimab treatment. Following a 9-week washout, all PROs approached baseline values. Interpretation: Continued inhibition of the classical complement pathway with sutimlimab results in meaningful long-term improvements in PROs (fatigue and QoL) in patients with CAD. Funding: Sanofi.

Long-term efficacy and safety of continued complement C1s inhibition with sutimlimab in cold agglutinin disease: CADENZA study Part B.

Background: Cold agglutinin disease (CAD) is a rare autoimmune haemolytic anaemia mediated by the classical complement pathway (CP). Sutimlimab selectively targets complement C1s inhibiting classical CP activation. In CADENZA Part A (26-weeks), a placebo-controlled study in patients without recent transfusion history, sutimlimab reduced haemolysis, anaemia, and fatigue, and was generally well tolerated. Methods: The CADENZA study (NCT03347422) started in March 2018 (Part A) and completed in December 2021 (Part B). All patients in Part B were eligible to receive sutimlimab for up to 1 year after the last patient completed Part A. Efficacy and safety was assessed throughout Part B, until the last on-treatment visit with available assessment (LV), and after a 9-week washout. Findings: In total, 32/39 patients completed Part B; median treatment duration: 99 weeks. Similar sustained improvements in haemolysis, anaemia, and quality of life were observed in patients switching to sutimlimab and those continuing sutimlimab. Mean LV values for the combined group (ie, placebo-to-sutimlimab group and sutimlimab-to-sutimlimab group) improved from baseline for haemoglobin (≥11.0 g/dL on-treatment vs 9.3 g/dL at baseline), bilirubin (≤20.0 µmol/L on-treatment vs 35.0 µmol/L at baseline), and FACIT-Fatigue scores. Following a 9-week washout, inhibition of CP activity was reversed, and haemolytic markers approached baseline levels. Overall, sutimlimab was generally well tolerated throughout the study. No patients developed systemic lupus erythematosus or meningococcal infections. During the 9-week washout, most adverse events could be attributed to recurrence of underlying CAD. Interpretation: The CADENZA Part B results support the sustained efficacy and safety of sutimlimab for treatment of CAD; however, upon discontinuation disease activity reoccurs. Funding: Sanofi.

Long-term sutimlimab improves quality of life for patients with cold agglutinin disease: CARDINAL 2-year follow-up.

Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia with a substantial burden on patient's quality of life. CARDINAL was a 2-part, open-label, single-arm, multicenter phase 3 study evaluating the C1s inhibitor, sutimlimab, for treatment of CAD. Part A consisted of the pivotal study phase, with the part B extension phase assessing long-term safety and durability of response including patient-reported outcomes, which is the focus of this report. Altogether, 22 patients continued from part A to part B, majority female (68.2%) with a median age of 71.5 years (range, 55-85). Throughout treatment, score improvement on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale exceeded a predefined, group-level clinically important change of ≥5 points vs baseline, with a mean (standard error [SE]) change of 11.7 (3.7) points at week 135. The 12-Item Short Form Health Survey physical and mental component scores remained above baseline, with week 123 mean change (SE) exceeding clinically important changes of 3.9 for physical and 2.8 for mental component scores at 4.7 (2.8) and 3.8 (5.7) points, respectively. EuroQol Visual Analogue Scale, scoring patients' self-rated health, also remained above baseline with a change of 17.1 (5.6) points at week 135. Patient Global Impression of (fatigue) Severity improved vs baseline, corroborating FACIT-Fatigue scores. Patient Global Impression of Change indicated a reduction in perceived disease burden. Data from CARDINAL part B support sustained alleviation of CAD disease burden after long-term treatment with sutimlimab over 2 years, returning toward baseline upon treatment cessation. This trial was registered at www.clinicaltrials.gov as #NCT03347396.

Sustained inhibition of complement C1s with sutimlimab over 2 years in patients with cold agglutinin disease.

Cold agglutinin disease (CAD) is a rare, autoimmune, classical complement pathway (CP)-mediated hemolytic anemia. Sutimlimab selectively inhibits C1s of the C1 complex, preventing CP activation while leaving the alternative and lectin pathways intact. In Part A (26 weeks) of the open-label, single-arm, Phase 3 CARDINAL study in patients with CAD and a recent history of transfusion, sutimlimab demonstrated rapid effects on hemolysis and anemia. Results of the CARDINAL study Part B (2-year extension) study, described herein, demonstrated that sutimlimab sustains improvements in hemolysis, anemia, and quality of life over a median of 144 weeks of treatment. Mean last-available on-treatment values in Part B were improved from baseline for hemoglobin (12.2 g/dL on-treatment versus 8.6 g/dL at baseline), bilirubin (16.5 µmol/L on-treatment versus 52.1 µmol/L at baseline), and FACIT-Fatigue scores (40.5 on-treatment versus 32.4 at baseline). In the 9-week follow-up period after sutimlimab cessation, CP inhibition was reversed, and hemolytic markers and fatigue scores approached pre-sutimlimab values. Overall, sutimlimab was generally well tolerated in Part B. All 22 patients experienced ≥1 treatment-emergent adverse event (TEAE); 12 (54.5%) patients experienced ≥1 serious TEAE, including seven (31.8%) with ≥1 serious infection. Three patients discontinued due to a TEAE. No patients developed systemic lupus erythematosus or meningococcal infections. After cessation of sutimlimab, most patients reported adverse events consistent with recurrence of CAD. In conclusion, the CARDINAL 2-year results provide evidence of sustained sutimlimab effects for CAD management, but that disease activity reoccurs after treatment cessation. NCT03347396. Registered November 20, 2017.

Biomarkers and laboratory assessments for monitoring the treatment of patients with paroxysmal nocturnal hemoglobinuria: Differences between terminal and proximal complement inhibition.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening, acquired disease in which blood cells lacking complement regulatory proteins are destroyed because of uncontrolled complement activity. Since 2007, terminal complement inhibitors have revolutionized the treatment of this disease. However, patients treated with these inhibitors can still experience anemia because of C3-mediated extravascular hemolysis and clinically relevant levels of breakthrough or residual intravascular hemolysis. Proximal complement inhibitors, which are only just beginning to emerge, have the potential to address this problem by targeting components of the pathway upstream of C5, thereby protecting patients against both intra- and extravascular hemolysis. In this review, we describe different biomarkers that can be used to monitor complement pathway blockade and discuss key laboratory assessments for evaluating treatment efficacy. We also consider how these assessments are affected by each class of inhibitor and highlight how evolving treatment goals may influence the relative importance of these assessments.

Sutimlimab provides clinically meaningful improvements in patient-reported outcomes in patients with cold agglutinin disease: Results from the randomised, placebo-controlled, Phase 3 CADENZA study.

Cold agglutinin disease (CAD) is a rare chronic autoimmune haemolytic anaemia, driven mainly by classical complement pathway activation, leading to profound fatigue and poor quality of life. In the Phase 3 CADENZA trial, sutimlimab-a C1s complement inhibitor-rapidly halted haemolysis, increased haemoglobin levels and improved fatigue versus placebo in patients with CAD without a recent history of transfusion. Patient-reported outcomes (PROs) included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), 12-Item Short Form Health Survey (SF-12), EuroQol visual analogue scale (EQ-VAS), Patient Global Impression of Change (PGIC) and Patient Global Impression of (fatigue) Severity (PGIS). Sutimlimab resulted in significant rapid and meaningful improvements versus placebo in PROs. From Week 1, the FACIT-Fatigue mean score increased >5 points above baseline (considered a clinically important change [CIC]). Least-squares (LS) mean change in FACIT-Fatigue score from baseline to treatment assessment timepoint was 10.8 vs. 1.9 points (sutimlimab vs. placebo; p < 0.001). Improvements in physical (PCS) and mental (MCS) component scores of the SF-12 were also considered CICs (LS mean changes from baseline to Week 26: PCS 5.54 vs. 1.57 [p = 0.064]; MCS 5.65 vs. -0.48 [p = 0.065]). These findings demonstrate that in addition to improving haematologic parameters, sutimlimab treatment demonstrates significant patient-reported benefits. Study registered at www.clinicaltrials.gov: NCT03347422.

Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial.

BACKGROUND: In the PEGASUS trial, the complement C3 inhibitor, pegcetacoplan, showed superiority to eculizumab in improving haematological outcomes in adult patients with paroxysmal nocturnal haemoglobinuria and suboptimal response to eculizumab at 16 weeks. The aim of the open-label period was to evaluate the long-term efficacy and safety of pegcetacoplan through to 48 weeks. METHODS: PEGASUS was a phase 3, randomised, open-label, active-comparator controlled trial conducted in 44 centres in Australia, Belgium, Canada, France, Germany, Japan, Russia, South Korea, Spain, the UK, and the USA. Eligible participants were aged 18 years or older, had paroxysmal nocturnal haemoglobinuria, and had a haemoglobin concentration of less than 10·50 g/dL after 3 months or longer of stable eculizumab treatment. After a 4-week run-in with eculizumab plus pegcetacoplan, patients were randomly assigned (1:1) by interactive response technology to pegcetacoplan (1080 mg subcutaneously twice weekly) or eculizumab (according to their regimen at enrolment) for 16 weeks and could continue to the open-label period (32 weeks of pegcetacoplan monotherapy [pegcetacoplan-to-pegcetacoplan] or 28 weeks of pegcetacoplan monotherapy [eculizumab-to-pegcetacoplan]). Randomisation was stratified by platelet count and number of previous blood transfusions. The primary endpoint was change from baseline in haemoglobin at week 16, which has previously been reported. The outcomes of the open-label period (week 16 to week 48) are reported here. At 48 weeks, efficacy (including mean haemoglobin concentration and quality of life measured on the Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue scale) was assessed in the intention-to-treat population and safety was assessed per protocol. This trial was registered with ClinicalTrials.gov, NCT03500549, and has been completed. FINDINGS: Between June 14, 2018, and Nov 14, 2019, 80 patients were randomly assigned to receive treatment with pegcetacoplan (41 patients) or eculizumab (39 patients). Most participants were women (49 [61%]) and 31 (39%) were men; 12 (15%) were Asian, two (3%) were Black, 49 (61%) were White, and 17 (21%) were another race or did not report their race. The open-label period had 77 participants (38 pegcetacoplan-to-pegcetacoplan, 39 eculizumab-to-pegcetacoplan). Patients in the pegcetacoplan-to-pegcetacoplan group maintained high mean haemoglobin concentrations between 16 weeks (11·54 g/dL [SD 1·96]) and 48 weeks (11·30 g/dL [1·77]; p=0·14). Patients in the eculizumab-to-pegcetacoplan group had significantly greater mean haemoglobin concentrations at 48 weeks (11·57 g/dL [2·21]) versus 16 weeks (8·58 g/dL [0·96]; p<0·0001). Clinically meaningful improvements in FACIT-Fatigue scores were observed at 48 weeks, with a mean change from baseline for all patients receiving pegcetacoplan monotherapy of 9·89 points (SD 9·63), for patients in the pegcetacoplan-to-pegcetacoplan group mean 10·14 points (9·06), and for patients in the eculizumab-to-pegcetacoplan group mean 9·62 points (10·34). During the entire study period, 13 (16%) of 80 patients discontinued treatment (three [7%] of 41 through to week 16 due to breakthrough haemolysis, and ten [13%] of 77 due to severe treatment-emergent adverse events) and 18 patients (eight pegcetacoplan-to-pegcetacoplan, ten eculizumab-to-pegcetacoplan) had at least one serious treatment-emergent adverse event during the open-label period, four were considered to be related to pegcetacoplan treatment. The most common treatment-emergent adverse events (in ≥10% patients) among both pegcetacoplan-treated groups during the open-label period were injection site reactions (in 20 [26%] of 77 patients), haemolysis (15 [19%]), nasopharyngitis (12 [16%]), and diarrhoea (ten [13%]). No treatment-related deaths occurred throughout the duration of the study. INTERPRETATION: The durability of improved haematological outcomes and favourable safety profile over 48 weeks of treatment suggests that pegcetacoplan has the potential to improve treatment benefit and alter treatment goals in patients with paroxysmal nocturnal haemoglobinuria. FUNDING: Apellis Pharmaceuticals.

Sutimlimab improves quality of life in patients with cold agglutinin disease: results of patient-reported outcomes from the CARDINAL study.

Patients with cold agglutinin disease (CAD) experience fatigue and poor quality of life. However, previous CAD-related studies have not explored patient-reported outcomes such as the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Sutimlimab, a C1s complement inhibitor, has been shown to halt haemolysis in CAD. Here, we present 26-weeks' patient-reported data from CARDINAL Part A (ClinicalTrials.gov, NCT03347396), which assessed efficacy and safety of sutimlimab in patients with CAD and recent history of transfusion. Aside from measuring changes in haemolytic markers, FACIT-Fatigue was measured at the treatment assessment timepoint (TAT; average of weeks 23, 25, and 26). Exploratory endpoints included the change in EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L) and the 12-Item Short Form Health Survey (SF-12) at TAT, and Patient Global Impression of Change (PGIC), and Patient Global Impression of (fatigue) Severity (PGIS) at week 26. Mean (range) FACIT-Fatigue scores increased from 32.5 (14.0-47.0) at baseline (a score indicative of severe fatigue) to 44.3 (28.0-51.0) at TAT. Considerable improvements were reported for EQ-5D-5L at TAT, SF-12 scores at TAT, and PGIC and PGIS scores at week 26. Sutimlimab treatment resulted in sustained improvements in symptoms of fatigue and overall quality of life in patients with CAD. NCT03347396. Registered 20 November, 2017.

Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial.

Sutimlimab, a first-in-class humanized immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits the classical complement pathway at C1s, rapidly halted hemolysis in the single-arm CARDINAL study in recently transfused patients with cold agglutinin disease (CAD). CADENZA was a 26-week randomized, placebo-controlled phase 3 study to assess safety and efficacy of sutimlimab in patients with CAD without recent (within 6 months prior to enrollment) transfusion history. Forty-two patients with screening hemoglobin ≤10 g/dL, elevated bilirubin, and ≥1 CAD symptom received sutimlimab (n = 22) or placebo (n = 20) on days 0 and 7 and then biweekly. Composite primary endpoint criteria (hemoglobin increase ≥1.5 g/dL at treatment assessment timepoint [mean of weeks 23, 25, 26], avoidance of transfusion, and study-prohibited CAD therapy [weeks 5-26]) were met by 16 patients (73%) on sutimlimab, and 3 patients (15%) on placebo (odds ratio, 15.9 [95% confidence interval, 2.9, 88.0; P < .001]). Sutimlimab, but not placebo, significantly increased mean hemoglobin and FACIT-Fatigue scores at treatment assessment timepoint. Sutimlimab normalized mean bilirubin by week 1. Improvements correlated with near-complete inhibition of the classical complement pathway (2.3% mean activity at week 1) and C4 normalization. Twenty-one (96%) sutimlimab patients and 20 (100%) placebo patients experienced ≥1 treatment-emergent adverse event. Headache, hypertension, rhinitis, Raynaud phenomenon, and acrocyanosis were more frequent with sutimlimab vs placebo, with a difference of ≥3 patients between groups. Three sutimlimab patients discontinued owing to adverse events; no placebo patients discontinued. These data demonstrate that sutimlimab has potential to be an important advancement in the treatment of CAD. This trial was registered at www.clinicaltrials.gov as #NCT03347422.

Acute ST-Segment Elevation Myocardial Infarction as Initial Presentation of Atypical Hemolytic-Uremic Syndrome.

A young woman presented with an acute ST-segment elevation myocardial infarction. Her clinical course was complicated by cardiogenic shock and acute renal failure. Work-up revealed thrombocytopenia and hemolytic anemia. A diagnosis of atypical hemolytic-uremic syndrome was made on the basis of clinical and pathological findings. (Level of Difficulty: Intermediate.).

Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria.

Eculizumab is first-line treatment for paroxysmal nocturnal hemoglobinuria (PNH); however, approximately 11%-27% of patients may experience breakthrough hemolysis (BTH) on approved doses of eculizumab. Ravulizumab, a new long-acting C5 inhibitor with a four-times longer mean half-life than eculizumab, provides immediate, complete, and sustained C5 inhibition over 8-week dosing intervals. In two phase 3 studies, ravulizumab was noninferior to eculizumab (Pinf ≤0.0004) for the BTH endpoint; fewer patients experienced BTH with ravulizumab versus eculizumab in both studies (301 [complement inhibitor-naive patients], 4.0% vs 10.7%; 302 [patients stabilized on eculizumab at baseline], 0% vs 5.1%). In the current analysis, patient-level data were evaluated to assess causes and clinical parameters associated with incidents of BTH reported during the 26-week treatment periods in the ravulizumab phase 3 PNH studies. Of the five BTH events occurring in ravulizumab-treated patients across the studies, none were temporally associated with suboptimal C5 inhibition (free C5 ≥0.5 µg/mL); four (80.0%) were temporally associated with complement-amplifying conditions (CACs). Of the 22 events occurring in eculizumab-treated patients, eleven were temporally associated with suboptimal C5 inhibition, including three events also associated with concomitant infection. Six events were associated with CACs only. Five events were unrelated to free C5 elevation or reported CACs. These results suggest that the immediate, complete, and sustained C5 inhibition achieved through weight-based dosing of ravulizumab reduces the risk of BTH by eliminating BTH associated with suboptimal C5 inhibition in patients with PNH. Clinicaltrials.gov identifiers: Study 301, NCT02946463; Study 302, NCT03056040.

Cost burden of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria receiving ravulizumab versus eculizumab.

Objectives: Although complement inhibition is highly effective, patients with paroxysmal nocturnal hemoglobinuria (PNH) may experience intravascular breakthrough hemolysis (BTH). Underlying causes may include elevated free C5, pregnancy, or non-pregnancy complement-activating conditions (e.g. infections). This study compared BTH-related resource utilization and costs in PNH patients treated with eculizumab versus ravulizumab. Methods: A cost model was developed using data from a targeted literature review and a survey of experienced clinicians. Costs associated with BTH episodes were calculated by cause and weighted by the proportion attributed to each cause and the cost of treating each episode. The model captured direct medical costs in 2018 US dollars. Annual BTH-related healthcare resource utilization was also calculated. Results: BTH episodes in the literature were commonly associated with elevated lactate dehydrogenase and aspartate aminotransferase, hemoglobinuria, transfusion needs, and/or recurrence of PNH symptoms. The majority of BTH management costs in eculizumab-treated patients related to changing from the approved dosing regimen following an episode of BTH, rather than acute management. No ongoing dosing changes were expected for ravulizumab-treated patients following episodes of BTH, substantially reducing its ongoing management costs. Resource utilization was greater for eculizumab-treated patients than ravulizumab-treated patients due to higher incidence of BTH, and risk of elevated free C5-related BTH. Total incremental cost was substantially lower for ravulizumab- vs eculizumab-treated patients ($407 vs $9379); results were consistent when pregnant women were not included ($386 vs $3472). Conclusion: Overall resource use and costs for BTH are estimated to be lower for PNH patients receiving ravulizumab compared with eculizumab.

Multidrug Therapy for Refractory Immune Thrombocytopenia in Pregnancy.

BACKGROUND: Severe immune thrombocytopenia complicating pregnancy may require treatment beyond first-line medications (intravenous immunoglobulins or corticosteroids), but there is a paucity of literature on the use of such second-line agents in pregnancy. CASE: The patient is a 29-year-old woman with early-onset severe immune thrombocytopenia at 13 weeks of gestation. Maternal platelet counts reached a nadir of less than 5×10/L. The thrombocytopenia persisted despite first-line medications. Romiplostim, rituximab, and azathioprine were added to the therapeutic regimen. Platelet counts eventually stabilized at greater than 150×10/L before delivery. After delivery at term, the neonate had transient B-cell suppression, which was presumed to be secondary to rituximab, but was otherwise doing well and meeting all milestones at 7 months of age. CONCLUSION: The addition of second-line agents was associated with sustained elevation in maternal platelet counts and may have obviated the need for splenectomy.

A Retrospective Study of the Combination of Rituximab, Cyclophosphamide and Dexamethasone for the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia.

The combination of rituximab, cyclophosphamide, and dexamethasone (RCD) is highly effective in the treatment of warm autoimmune hemolytic anemia (WAIHA) associated with chronic lymphocytic leukemia (CLL). We treated a cohort of patients with relapsed/refractory WAIHA, without CLL, with RCD. The primary objective was to evaluate the overall response (OR) of RCD therapy. Complete response (CR) was defined as a hemoglobin (Hgb) ≥12 g/dL. Partial response (PR) was defined as Hgb 10-11.9 g/dL or ≥2 g/dL increase in Hgb. Sustained response was defined as Hgb ≥10 g/dL with no treatment changes. A total of 16 patients with relapsed/refractory WAIHA received RCD (7 primary WAIHA, 9 secondary WAIHA) for a median of 4 cycles (range: 2-6). The median pretreatment Hgb was 10.0 g/dL (range: 4.3-12.2). The median best Hgb achieved was 12.5 g/dL (range: 10.6-15.1) with a median of 2 cycles until best Hgb response. The OR was 94% (11 CR, 4 PR). Two immunocompromised patients were admitted for infections during RCD treatment. There were no deaths during the treatment or follow-up period. Following a response to RCD, 4 patients received noncorticosteroid immune modulation therapy and 4 patients continued on corticosteroid therapy. Seven patients received no additional treatment.

Ethnic and racial difference in Helicobacter pylori infection in patients with immune thrombocytopenia treated at a major urban medical center.

Immune thrombocytopenia (ITP) is an autoimmune disorder with a complex immunopathology and pathogenesis characterized by thrombocytopenia and bleeding manifestations. The disorder is separated into primary (idiopathic) ITP and secondary ITP, when associated with other immune or lymphoproliferative disorders and certain chronic infections. Helicobacter pylori (H. pylori) is a recognized bacterial cause of ITP. In regions with high prevalence of infection, bacterial eradication has resulted in improvement in platelet count. However, the prevalence of H. pylori infection and response to antimicrobial therapy in North American ITP patients is reportedly low. We evaluated the prevalence of H. pylori infection in ITP patients diagnosed and treated at a large urban medical center. Eighty-two patients were screened for H. pylori, by stool antigen (n = 54), H. pylori breath test (n = 11), and H. pylori antibodies (n = 16), of which 15 (18.3%) were white non-Hispanic (WNH), 55 (67%) Hispanic (H), 8 (9.8%) Asian (A), and 4 (4.9%) African-American (AA). Of the screened patients, 36/82 (43.9%) tested positive for H. pylori. The prevalence of H. pylori infection within the represented ethnic groups was 2/15 (13%) WNH, 29/55 (52.7%) H, 3/8 (37.5%) A, and 2/4 (50%) AA. There was a significant difference in prevalence of infection comparing WNH and H patients (p = 0.007). There were 36 treated patients, with H. pylori eradication documented in 26 patients. Fifteen of the 26 patients were evaluable for response with 8 of 15 (53%) having clinical responses, 6 complete responses, and 2 partial responses. Our study demonstrates an increased prevalence of H. pylori infection in the Hispanic ITP population with a reasonable platelet response among patients with H. pylori eradication.

Autoimmune Hemolytic Anemia.

Autoimmune hemolytic anemia is an acquired autoimmune disorder resulting in the production of antibodies directed against red blood cell antigens causing shortened erythrocyte survival. The disorders can present as a primary disorder (idiopathic) or secondary to other autoimmune disorders, malignancies, or infections. Treatment involves immune modulation with corticosteroids and other agents.

Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria.

BACKGROUND: Eculizumab, a humanized monoclonal antibody against complement protein C5 that inhibits terminal complement activation, has been shown to prevent complications of paroxysmal nocturnal hemoglobinuria (PNH) and improve quality of life and overall survival, but data on the use of eculizumab in women during pregnancy are scarce. METHODS: We designed a questionnaire to solicit data on pregnancies in women with PNH and sent it to the members of the International PNH Interest Group and to the physicians participating in the International PNH Registry. We assessed the safety and efficacy of eculizumab in pregnant patients with PNH by examining the birth and developmental records of the children born and adverse events in the mothers. RESULTS: Of the 94 questionnaires that were sent out, 75 were returned, representing a response rate of 80%. Data on 75 pregnancies in 61 women with PNH were evaluated. There were no maternal deaths and three fetal deaths (4%). Six miscarriages (8%) occurred during the first trimester. Requirements for transfusion of red cells increased during pregnancy, from a mean of 0.14 units per month in the 6 months before pregnancy to 0.92 units per month during pregnancy. Platelet transfusions were given in 16 pregnancies. In 54% of pregnancies that progressed past the first trimester, the dose or the frequency of use of eculizumab had to be increased. Low-molecular-weight heparin was used in 88% of the pregnancies. Ten hemorrhagic events and 2 thrombotic events were documented; both thrombotic events occurred during the postpartum period. A total of 22 births (29%) were premature. Twenty cord-blood samples were examined for the presence of eculizumab; the drug was detected in 7 of the samples. A total of 25 babies were breast-fed, and in 10 of these cases, breast milk was examined for the presence of eculizumab; the drug was not detected in any of the 10 breast-milk samples. CONCLUSIONS: Eculizumab provided benefit for women with PNH during pregnancy, as evidenced by a high rate of fetal survival and a low rate of maternal complications. (ClinicalTrials.gov number, NCT01374360.).