0
selected
-
1.
Clinical significance of C-reactive protein levels in predicting responsiveness to iron therapy in patients with inflammatory bowel disease and iron deficiency anemia
Iqbal T, Stein J, Sharma N, Kulnigg-Dabsch S, Vel S, Gasche C
Digestive Diseases & Sciences. 2015;60((5)):1375-81.
Abstract
BACKGROUND Iron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD). In clinical practice, many patients receive initial treatment with iron tablets although intravenous (i.v.) iron supplementation is often preferable. AIM: This study investigated whether systemic inflammation at initiation of treatment (assessed by C-reactive protein [CRP] and interleukin-6 [IL-6] measurements) predicts response to iron therapy. METHODS Data from a previously published phase III trial were retrospectively analyzed after stratification of patients according to baseline CRP (>4 vs. <4 mg/L) and IL-6 (>6 vs. <6 pg/mL) levels. The study population consisted of patients with Crohn's disease or ulcerative colitis and IDA (Hb < 110 g/L and TSAT < 20 % or serum ferritin < 100 ng/mL), randomized to either oral (ferrous sulfate) or i.v. iron (ferric carboxymaltose). RESULTS A total of 196 patients were evaluated (oral iron: n = 60; i.v. iron: n = 136). Baseline CRP and IL-6 levels were independent of patients' initial Hb levels and iron status (serum ferritin and TSAT; all p > 0.05). Among iron tablet-treated patients, Hb increase was significantly smaller in the high- versus low-CRP subgroup (1.1 vs. 2.0, 2.3 vs. 3.1, and 3.0 vs. 4.0 g/dL at weeks 2, 4, and 8, respectively; all p < 0.05). Differences were less pronounced with stratification according to baseline IL-6. Response to i.v. iron was mainly independent of inflammation. CONCLUSIONS Patients with high baseline CRP achieved a lower Hb response with oral iron therapy. Our results suggest that CRP may be useful to identify IBD patients who can benefit from first-line treatment with i.v. iron to improve their IDA.
-
2.
Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: results from a phase-3 clinical trial program
Gasche C, Ahmad T, Tulassay Z, Baumgart DC, Bokemeyer B, Buning C, Howaldt S, Stallmach A
Inflammatory Bowel Diseases. 2015;21((3):):579-88.
-
-
Free full text
-
Abstract
BACKGROUND Iron deficiency anemia (IDA) is frequently seen in inflammatory bowel disease. Traditionally, oral iron supplementation is linked to extensive gastrointestinal side effects and possible disease exacerbation. This multicenter phase-3 study tested the efficacy and safety of ferric maltol, a complex of ferric (Fe) iron with maltol (3-hydroxy-2-methyl-4-pyrone), as a novel oral iron therapy for IDA. METHODS Adult patients with quiescent or mild-to-moderate ulcerative colitis or Crohn's disease, mild-to-moderate IDA (9.5-12.0 g/dL and 9.5-13.0 g/dL in females and males, respectively), and documented failure on previous oral ferrous products received oral ferric maltol capsules (30 mg twice a day) or identical placebo for 12 weeks according to a randomized, double-blind, placebo-controlled study design. The primary efficacy endpoint was change in hemoglobin (Hb) from baseline to week 12. Safety and tolerability were assessed. RESULTS Of 329 patients screened, 128 received randomized therapy (64 ferric maltol-treated and 64 placebo-treated patients) and comprised the intent-to-treat efficacy analysis: 55 ferric maltol patients (86%) and 53 placebo patients (83%) completed the trial. Significant improvements in Hb were observed with ferric maltol versus placebo at weeks 4, 8, and 12: mean (SE) 1.04 (0.11) g/dL, 1.76 (0.15) g/dL, and 2.25 (0.19) g/dL, respectively (P < 0.0001 at all time-points; analysis of covariance). Hb was normalized in two-thirds of patients by week 12. The safety profile of ferric maltol was comparable with placebo, with no impact on inflammatory bowel disease severity. CONCLUSIONS Ferric maltol provided rapid clinically meaningful improvements in Hb and showed a favorable safety profile, suggesting its possible use as an alternative to intravenous iron in IDA inflammatory bowel disease.
-
3.
Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial
Kulnigg-Dabsch S, Schmid W, Howaldt S, Stein J, Mickisch O, Waldhor T, Evstatiev R, Kamali H, Volf I, Gasche C
Inflammatory Bowel Diseases. 2013;19((8):):1609-16.
Abstract
BACKGROUND Secondary thrombocytosis is a common clinical feature. In patients with cancer, it is a risk factor for venous thromboembolic events. In inflammatory bowel disease (IBD), thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population. Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis. Here, we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis. METHODS We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L). Changes in platelet counts, hemoglobin, iron parameters, disease activity, megakaryopoietic growth factors, erythropoietin, and platelet activity were assessed. Patients received placebo or up to 1500 mg iron as FCM. Endpoints were evaluated at week 6. RESULTS A total of 26 patients were included in the study, 15 patients were available for the per protocol analysis. A drop in platelets >25% (primary endpoint) was observed in 4 of 8 (50%, iron group) and 1 of 7 patients (14%, placebo group, P = 0.143). Mean platelet counts dropped on FCM but not on placebo (536 G/L to 411 G/L versus 580 G/L to 559 G/L; P = 0.002). Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM. The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression. CONCLUSION FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.
-
4.
Rapid recurrence of IBD-associated anemia and iron deficiency after intravenous iron sucrose and erythropoietin treatment
Kulnigg S, Teischinger L, Dejaco C, Waldhör T, Gasche C
The American Journal of Gastroenterology. 2009;104((6):):1460-7.
Abstract
OBJECTIVES Anemia is a common complication of inflammatory bowel disease (IBD) and iron deficiency (ID) is its predominant cause. Therefore, oral and intravenous iron replacements are widely used. This study was performed to evaluate the frequency and timing of anemia and ID recurrence after a successful treatment cycle. METHODS Medical records of patients who had received iron sucrose with or without erythropoietin (EPO) in one of three prospective clinical trials that had been conducted at our center (Ann Intern Med 1997, Digestion 1999, and Am J Gastroenterol 2001) were analyzed for a 5-year follow-up period. The risk for recurrence of anemia (hemoglobin (Hb)<12/13 g per 100 ml) and ID (ferritin <30 microg/l) was evaluated by Kaplan-Meier analysis using the log-rank test. RESULTS Eighty-eight patients were available for analysis. Patients had received a mean iron dose of 2,500 mg (range 600-3,600 mg); 33 (37. 1%) patients had also received EPO. Anemia recurred in a median of 10 months (95% confidence interval (CI) 8-12) and ID recurred within 19 months (95% CI 11-28). The iron dose had no influence on recurrence of ID or anemia. ID (but not anemia) recurred faster in patients with a post-treatment ferritin level <100 microg/l (median 4 months, 95% CI 1-7) than in patients with ferritin level between 100 and 400 microg/l (median 11 months, 95% CI 6-16) and >400 microg/l (median 49 months, 95% CI 32-66; P<0. 001). CONCLUSIONS IBD-associated ID and anemia recur surprisingly fast, indicating that maintenance treatment may be needed in a portion of the patient population. Recurrence of ID (but not anemia) can be delayed by aiming for high post-treatment ferritin levels.
-
5.
A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial
Kulnigg S, Stoinov S, Simanenkov V, Dudar LV, Karnafel W, Garcia LC, Sambuelli AM, D'Haens G, Gasche C
The American Journal of Gastroenterology. 2008;103((5):):1182-92.
Abstract
BACKGROUND AIMS Anemia is a common complication of inflammatory bowel diseases (IBD) This multicenter study tested the noninferiority and safety of a new intravenous iron preparation, ferric carboxymaltose (FeCarb), in comparison with oral ferrous sulfate (FeSulf) in reducing iron deficiency anemia (IDA) in IBD. METHODS Two hundred patients were randomized in a 2:1 ratio (137 FeCarb:63 FeSulf) to receive FeCarb (maximum 1,000 mg iron per infusion) at 1-wk intervals until the patients' calculated total iron deficit was reached or FeSulf (100 mg b. i. d. ) for 12 wk. The primary end point was change in hemoglobin (Hb) from baseline to week 12. RESULTS The median Hb improved from 8. 7 to 12. 3 g/dL in the FeCarb group and from 9. 1 to 12. 1 g/dL in the FeSulf group, demonstrating noninferiority (P= 0. 6967). Response (defined as Hb increase of >2. 0 g/dL) was higher for FeCarb at week 2 (P= 0. 0051) and week 4 (P= 0. 0346). Median ferritin increased from 5. 0 to 323. 5 mug/L at week 2, followed by a continuous decrease in the FeCarb group (43. 5 mug/L at week 12). In the FeSulf group, a moderate increase from 6. 5 to 28. 5 mug/L at week 12 was observed. Treatment-related adverse events (AEs) occurred in 28. 5% of the FeCarb and 22. 2% of the FeSulf groups, with discontinuation of study medication due to AEs in 1. 5% and 7. 9%, respectively. CONCLUSIONS FeCarb is effective and safe in IBD-associated anemia. It is noninferior to FeSulf in terms of Hb change over 12 wk, and provides a fast Hb increase and a sufficient refill of iron stores.