Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial

BACKGROUND & AIMS: We assessed the relationship between antibodies to infliximab (ATI) and the loss of response postinfliximab, infusion reactions and, in a randomized trial, investigated whether intravenous hydrocortisone premedication can reduce ATI. METHODS: Initially, we prospectively evaluated clinical response, adverse events, and ATI levels in 53 consecutive patients with Crohn's disease who received 199 infliximab (5 mg/kg) infusions. Subsequently, 80 patients with Crohn's disease were randomized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions. The primary endpoint was reduction in median ATI levels at week 16. Analysis was by intention to treat. RESULTS: Nineteen of our initial 53 patients (36%) developed ATI, including all 7 patients with serious infusion reactions (median ATI level, 19.6 microg/mL). Eleven of 15 patients (73%) who lost their initial response were ATI positive compared with none of 21 continuous responders, (8.9 vs. 0.7 microg/mL, P < 0.0001). Administering a second infusion within 8 weeks of the first (OR, 0.13; 95% CI, 0.03-0.5; P = 0.0007) or concurrent immunosuppressants (OR, 0.19; 95% CI, 0.04-1.03; P = 0.007) significantly reduced ATI formation. In the placebo-controlled trial, ATI levels were lower at week 16 among hydrocortisone-treated patients (1.6 vs. 3.4 microg/mL, P = 0.02), and 26% of hydrocortisone-treated patients developed ATI compared with 42% of placebo-treated patients, P = 0.06. CONCLUSIONS: Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level. Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation. Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions

Clinical experience with infliximab therapy in 100 patients with Crohn's disease

OBJECTIVE: The aim of this study was to assess our clinical experience with infliximab, a monoclonal antitumor necrosis factor antibody, following its approval for treatment of refractory Crohn's disease (CD). METHODS: We followed 100 consecutive patients with CD (53 women and 47 men; mean age, 41 yr) who received a total of 233 infliximab (5 mg/kg) infusions. Adverse events were noted and clinical response assessed every 2 wk for 6 months after each infusion using the Harvey Bradshaw Index (HBI) for active disease, the Perianal Disease Activity Index (PDAI) for fistulous disease, and steroid withdrawal rates for steroid-sparing efficacy. RESULTS: Indications for therapy were active disease (n = 57), perianal fistulous disease (n = 33), and steroid dependency (n = 10). Significant infusion reactions occurred in 16 patients (6.9% of infusions) including anaphylactic shock in one patient. Fourteen patients experienced infectious adverse events, 13 of whom were on concurrent steroids. Sixty percent of patients with active disease experienced > or = 50% HBI reduction at 2 wk; mean duration of response, 8.2 wk. Three of 26 first-time nonresponders with active disease (12%) responded to a second infusion. Sixty-nine percent of patients with fistulous disease experienced >50% reduction in their PDAI at 2 wk; mean duration of response, 10.9 wk. Four of 10 steroid-dependent patients (40%) discontinued steroid therapy, one of whom recommenced steroid therapy at 24 wk. CONCLUSIONS: Our clinical response rates mirror the efficacy reported in the controlled trials for active and fistulous disease. Steroid-sparing efficacy was seen in 40% of steroid-dependent patients. Concurrent steroids did not reduce the risk of significant infusion reactions (6.9%), but did increase the risk of infections

Safety and efficacy of E coli enterotoxin adjuvant for urease-based rectal immunization against Helicobacter pylori

Low dose E. coli heat-labile enterotoxin (LT), delivered orally or enterically, has been used as an adjuvant for Helicobacter pylori (H. pylori) urease in healthy adults. In this study we aim to test the safety and adjuvant efficacy of LT delivered rectally together with recombinant H. pylori urease. Eighteen healthy adults without present or past H. pylori infection were enrolled in a double blind, randomized, ascending dose study to receive either urease (60 mg), or urease (60 mg) + LT (5 or 25 microg). The immunization preparation was administered per rectum on days 0, 14 and 28. Serum, stool and saliva anti-urease and anti-LT IgG and IgA antibodies (Abs) were measured and urease-specific and LT-specific antigen secreting cells (ASCs) were counted in peripheral blood at baseline and 7 (ASC counts) or 14 days (antibody levels) after each dosing. Peripheral blood lymphoproliferation assays were also performed at baseline and at the end of the study.Rectally delivered urease and LT were well tolerated. Among the 12 subjects assigned to urease+LT, 2 (16.7%) developed anti-urease IgG Abs, 1 (8.3%) developed anti-urease IgA Abs, and 3 (25%) showed urease-specific IgA(+) ASCs. Immune responses to LT were more vigorous, especially in subjects exposed to 5 microg LT. In the urease+ 5 microg LT group, anti-LT IgG and IgA Abs developed in 60 and 80% of the subjects, respectively, while LT-specific IgG(+) and IgA(+) ASCs were detected in all subjects. The magnitude of the anti-LT response was much higher than the response to urease. No IgA anti-urease or anti-LT Abs were detected in stool or saliva and lymphocyte proliferative responses to urease were unsatisfactory. In conclusion, rectal delivery of 5 microg LT is safe and induces vigorous systemic anti-LT immune responses. Further studies are needed to determine if LT can be an effective adjuvant for rectally delivered antigens

Improving the Tolerance to Salinity Stress in Lettuce Plants (<i>Lactuca sativa</i> L.) Using Exogenous Application of Salicylic Acid, Yeast, and Zeolite

Salinity is among the most limiting factors of crop production worldwide. This study aims to investigate the influence of the exogenous application of zeolite, yeast, and salicylic acid in alleviating the negative effect of salt stress under field conditions. Lettuce plants (Lactuca sativa L. cv. Batavia) were tested in a split-plot arrangement replicated three times. The salt stress was applied as a whole-plot factor in the concentrations (0 mM, 50 mM, 100 mM, and 150 mM NaCl). After 28 days of sowing, the plants were sprayed twice during the foliage growth with (control, salicylic acid 0.02%, yeast extract 3%, and zeolite 0.5%) as a split-plot factor. The length of roots and shoots, the number and area of leaves, and the biomass accumulation (dry and fresh weights) were measured 50 days after sowing. The concentrations of total soluble sugars, proline, Chlorophylls a and b in leaves have also been quantified. Salt stress significantly reduced the growth and the total chlorophyll of the lettuce plants (p p p < 0.05) but with lower proline, sugar, and chlorophyll contents. In general, foliar spray of yeast extract may offer a good alternative source of nutrients through leaves, leading to a better tolerance of the high salt stress exerted on roots

Plant Growth-Promoting Potential of Entomopathogenic Fungus <i>Metarhizium pinghaense</i> AAUBC-M26 under Elevated Salt Stress in Tomato

Entomopathogenic fungi Metarhizium species are generally employed to manage the soil-dwelling stage of insect pests, and are known for their rhizocompetency property. Since this fungus is typically recommended for use in soil, it could potentially be investigated as a bioinoculant to reduce abiotic stress, such as salinity, along with improved plant growth promotion. Salt stress tolerance potential of native Metarhizium isolates was evaluated based on mycelial fresh weight, dry weight, and spore yield. All the isolates were found to tolerate NaCl concentrations (50 mM, 100 mM, 150 mM, 200 mM, 250 mM, and 300 mM) supplemented in the culture medium. Metarhizium anisopliae (AAUBC-M15) and Metarhizium pinghaense (AAUBC-M26) were found to be effective at tolerating NaCl stress up to 200 mM NaCl. These two isolates were analyzed in vitro for plant growth-promoting traits at elevated salt concentrations (100 and 200 mM NaCl). No significant effect on IAA production was reported with the isolate M. pinghaense (AAUBC-M26) (39.16 µg/mL) or in combination with isolate M. anisopliae (AAUBC-M15) (40.17 µg/mL) at 100 mM NaCl (38.55 µg/mL). The salinity stress of 100 mM and 200 mM NaCl had a significant influence on the phosphate solubilization activity, except in the co-inoculation treatment at 100 mM NaCl. The isolates were positive for ACC deaminase enzyme activity. An increase in salt concentration was accompanied by a steady and significant increase in chitinase enzyme activity. Total phenolics (149.3 µg/mL) and flavonoids (79.20 µg/mL) were significantly higher in the culture filtrate of Metarhizium isolates at 100 mM NaCl, and gradual decline was documented at 200 mM NaCl. M. pinghaense (AAUBC-M26) proved to be promising in reducing the salt stress in tomato seedlings during the nursery stage. In the pot culture experiment, the treatment comprising soil application + seedling root dip + foliar spray resulted in improved growth parameters of the tomato plant under salt stress. This study shows that Metarhizium, a fungus well known for controlling biotic stress brought on by insect pests, can also help plants cope with abiotic stress, such as salinity