Corticosteroids For Induction Of Remission Research Articles

DOP44 Tofacitinib versus corticosteroids for induction of remission in moderately active ulcerative colitis (ORCHID): A prospective randomized open-label pilot study

Abstract Background The exact positioning of tofacitinib in the therapeutic algorithm is still unclear. We evaluated the efficacy of tofacitinib in comparison to corticosteroids for induction of remission in patients with moderately active UC. Methods This was a randomized, parallel-group active-controlled pilot study comparing the efficacy and safety of corticosteroids and tofacitinib in inducing remission in adults with moderately active UC (defined as total Mayo clinic score 6-9). Patients were randomly assigned to receive corticosteroids (prednisolone, starting 40 mg daily and tapered by 5 mg every week over 8 weeks) or tofacitinib (10 mg twice daily) for 8 weeks. The primary endpoint was composite remission (defined as total Mayo clinic score≤2, with an endoscopic subscore of 0 and fecal calprotectin<100 mcg/g) at 8 weeks. Clinical remission (defined as Mayo clinic score ≤2) and clinical response (defined as a decrease of 30% in the Mayo clinic score from baseline or more and 3 or more points, along with either a rectal bleeding subscore of 0 or 1 or a decrease in the rectal bleeding subscore of 1 point or more) at week 8 were also evaluated. Follow-up assessments for efficacy and safety were done at weeks 2, 4, and 8. Results Seventy-eight patients (mean age 37.78±13.94 years, 42[53.84%] males; 43 assigned to tofacitinib and 35 to corticosteroids group) were enrolled. At week 8, there was no significant difference in the proportion of patients achieving composite remission in the two treatment groups (7 of 43, 16.28% in the tofacitinib group versus 3 of 35, 8.57% in the corticosteroid group; p=0.31). Clinical remission at week 8 was achieved in 18 of 43(41.86%) patients receiving tofacitinib and 13 of 35 (37.14%) patients receiving corticosteroids (p=0.67). Clinical response was seen in 28 of 43(65.12%) and 25 of 35(71.42%) patients in the tofacitinib and corticosteroid groups, respectively(p=0.55). No difference was observed in the median number of days required to achieve symptomatic remission between the two groups (10[IQR 7-18.75] and 10[IQR 5-12.5] days for tofacitinib and corticosteroids, respectively;p=0.25). One patient in the tofacitinib and corticosteroid group discontinued treatment due to the development of pulmonary tuberculosis and pustular acne, respectively. Another patient receiving tofacitinib developed herpes zoster. No serious adverse events or major adverse cardiovascular events were observed. Conclusion In patients with moderately active ulcerative colitis, there is no difference between the efficacy and safety of tofacitinib and corticosteroids for induction of remission. Tofacitinib can be used as a first-line therapy for inducing remission in moderately active UC. (CTRI Registration number: CTRI/2021/10/037641)

How does enteral nutrition compare with corticosteroids for induction of remission in Crohn's disease?

How does enteral nutrition compare with corticosteroids for induction of remission in Crohn's disease?

A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis

Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR=2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.

Systematic review: second‐generation vs. conventional corticosteroids for induction of remission in ulcerative colitis

Oral corticosteroids are the mainstay treatment for induction of ulcerative colitis remission in patients failing or intolerant to aminosalicylate therapy, but the poor tolerability profile of these drugs limits their usefulness. Second-generation, gut-selective corticosteroids may offer a safe alternative to systemic agents. To review the efficacy and safety of systemic and second-generation oral corticosteroids for the induction of remission in ulcerative colitis. The PubMed database was searched for randomised, controlled, and open-label trials of orally administered corticosteroids published between January 1950 and September 2015. Additional trials were identified from review of citation lists. Trials that compared oral corticosteroids with non-oral agents or in combination with agents other than aminosalicylates were excluded. Of the 240 studies identified, 21 were eligible for inclusion. Few trials directly compared oral systemic and second-generation corticosteroids (n = 4). Some second-generation corticosteroids had questionable efficacy vs. placebo or mesalazine (mesalamine), but beclomethasone dipropionate and budesonide MMX demonstrated a comparative benefit. Only beclomethasone dipropionate was similar to conventional corticosteroids for induction of remission and other clinical endpoints. Direct comparative trials for budesonide MMX were unavailable. Second-generation corticosteroids had an overall favourable safety profile, with minimal adverse effects on cardiovascular and metabolic parameters and a low incidence of adverse events. Beclomethasone dipropionate and budesonide MMX provide greater induction of remission in ulcerative colitis than placebo or mesalazine but additional active-comparator trials are needed to firmly establish the efficacy profile vs. systemic corticosteroids. Second-generation corticosteroids have a more favourable safety and tolerability profile than systemic corticosteroids.

Su1462 Oral Corticosteroids for Induction of Remission in Ulcerative Colitis: A Cochrane Review and Meta-Analysis

Su1462 Oral Corticosteroids for Induction of Remission in Ulcerative Colitis: A Cochrane Review and Meta-Analysis

Long-term Treatment of Patients With a History of Ulcerative Colitis Who Develop Gastritis and Pan-Enteritis After Colectomy

Ulcerative colitis (UC) is generally described as a superficial diffuse inflammation restricted to the colon and rectum. However, several case reports have described a distinct and rare type of UC-related pan-enteritis, typically occurring after colectomy. Corticosteroids are effective for induction of remission of this condition, but it is not clear how these patients should be managed long term. To further describe and define the entity of UC-related pan-enteritis and to investigate the efficacy of azathioprine for maintenance of remission. We describe 5 patients with superficial diffuse ulcerative inflammation of the stomach, small bowel, and pouch if present. Four of the 5 patients developed enteritis after colectomy for ulcerative pancolitis. Pathology showed severe mucosal inflammation with infiltration of neutrophils and plasma cells from the stomach to the ileum. Video capsule endoscopy in 1 patient confirmed the presence of mucosal inflammation throughout the small bowel. All patients were started on a standardized treatment with intravenous corticosteroids for induction of remission and azathioprine for maintenance therapy. The conditions of all the patients rapidly improved, and subsequently, 4 patients were in full remission on azathioprine monotherapy, despite failure of this UC therapy before surgery, whereas 1 patient continues to have a steroid-dependent disease. The outcomes of 5 cases of UC-related pan-enteritis as described in this report support a role for azathioprine in remission maintenance. Future research is needed to improve our understanding of this rare but distinct intestinal inflammatory disorder.

Oral Corticosteroids for Induction of Remission in Ulcerative Colitis

Purpose: Despite extensive use over many decades, regimens of steroids vary between clinicians. There is a lack of clarity of initial dosing, tapering pattern and duration of steroid treatment. Although most clinicians use once a day dosing, split dosing has been studied (Powell-Tuck 1987). Thus there is a need to clearly establish an evidence-based use of corticosteroids not only to maximise benefit but also reduce serious complications. In order to define its role further a Cochrane review will be undertaken. Methods: We included randomized controlled trials (RCTs) comparing oral corticosteroids versus placebo, administered to patients with confirmed ulcerative colitis. We searched 4 electronic databases and examined multiple sources of grey literature for eligible trials. Two independent investigators assessed trial eligibility and abstracted data. For each RCT we calculated the relative risk (RR) for each outcome and used a random effects model to pool the RRs. Results: Our search identified 9 citations that met our eligibility criteria. There were significantly greater rates of clinical (9 trials; 927 patients; RR 2.27; 95% CI 1.52-3.39; p=0.0001) and endoscopic (7 trials; 436 patients; RR 2.47; 95% CI 1.50-4.04; p=0.0003) remission with corticosteroids. Notably there was no significance increase in the occurrence of adverse events (3 trials, 218 patients; RR 2.74; 95% CI 0.31-23.85; p=0.36) and the withdrawal of patients due to adverse events (5 trials; 377 patients; RR 0.60; 95% CI 0.14-2.55; p=0.49). Conclusion: Our meta-analysis showed a significantly higher rates of clinical and endoscopic remission. There was no significant increase in the occurrence of adverse events and the withdrawal of patients secondary to adverse events.

768 Exclusive Enteral Nutrition in Paediatric Crohn's Disease

Background: The British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) guidance (October 2008) advocates the use of Exclusive Enteral Nutrition (EEN) as an alternative first line treatment to oral corticosteroids for induction of remission in paediatric Crohn's disease. Compared to steroids, EEN is not known to produce any harmful consequences. Aims: To assess whether EEN was being offered at two neighbouring district general hospitals (DGHs) in accordance with BSPGHAN standards and whether EEN courses were producing a remission rate similar to that in the literature. Methods: All patients on the Crohn's Disease Register were included. Data was collected from medical and dietician records and analysed using Microsoft Excel. Results: 95% children were offered and tolerated a full course of EEN. 83% EEN courses lasted 6-8 weeks. Remission was acheived in 78% overall (consistent with the literature). The length of period for food reintroduction was much more variable. Average number of dietician consultations for induction of remission and food reintroduction were also variable. 71% of those patients who achieved complete remission with EEN had a relapse ( 3 years). Conclusions: EEN was widely used in both the DGH settings. It was tolerated well and proved to be an effective treatment acheiving complete remission in 78% of patients. Our findings support the use of EEN as a first line treatment for paediatric crohn's disease. There is a need for more collabortive research and regular audits into the care of paediatric Crohn's disease patients.

Nutritional status and nutritional therapy in inflammatory bowel diseases

Underweight and specific nutrient deficiencies are frequent in adult patients with inflammatory bowel disease (IBD). In addition, a significant number of children with IBD, especially Crohn's disease (CD) have impaired linear growth. Nutrition has an important role in the management of IBD. In adults with CD, enteral nutrition (EN) is effective in inducing clinical remission of IBD, although it is less efficient than corticosteroids. Exclusive EN is an established primary therapy for pediatric CD. Limited data suggests that EN is as efficient as corticosteroids for induction of remission. Additional advantages of nutritional therapy are control of inflammation, mucosal healing, positive benefits to growth and overall nutritional status with minimal adverse effects. The available evidence suggests that supplementary EN may be effective also for maintenance of remission in CD. More studies are needed to confirm these findings. However, EN supplementation could be considered as an alternative or as an adjunct to maintenance drug therapy in CD. EN does not have a primary therapeutic role in ulcerative colitis. Specific compositions of enteral diets-elemental diets or diets containing specific components-were not shown to have any advantage over standard polymeric diets and their place in the treatment of CD or UC need further evaluation. Recent theories suggest that diet may be implicated in the etiology of IBD, however there are no proven dietary approaches to reduce the risk of developing IBD.

Predicting the Need for Azathioprine at First Presentation in Children With Inflammatory Bowel Disease

Although azathioprine usually is reserved for inflammatory bowel disease that proves difficult to control, routine early use has recently been advocated for children with Crohn disease. However, this practice carries with it an increased risk of adverse reactions. The objective of this study was to look for characteristics at first presentation that may identify those likely to benefit from early azathioprine. Study setting was a tertiary pediatric gastroenterology department. Retrospective cohort study of 156 children (93 Crohn disease, 47 ulcerative colitis, 16 indeterminate colitis), comparing characteristics at presentation in those who did and did not eventually require azathioprine. Azathioprine was reserved for patients with frequent relapses and steroid dependence/resistance. Twenty variables were examined, including patient and disease characteristics and initial treatment response. These were analysed using Kaplan-Meier survival curves, log-rank tests, and Cox proportional hazard regression. Median follow-up was 3.9 years (range 0.5-10.6 years). Azathioprine was used in 36% with Crohn disease and 40% with ulcerative colitis. Median time to commencing azathioprine was 14 months (range 3-77.5 months). Multifactorial analysis revealed an association with endoscopic colitis severity in Crohn disease (P < 0.02). However, only 50% with severe Crohn colitis actually needed azathioprine. There was an association with need for intravenous corticosteroids for induction of remission in Crohn disease (P < 0.006) and ulcerative colitis (P < 0.05). Of these patients, 75% required azathioprine. These findings support the early use of azathioprine in children who require intravenous corticosteroids to induce initial remission. No other characteristics examined were of clinical utility in predicting need for azathioprine.

Traditional corticosteroids for induction of remission in Crohn's disease

Historically, corticosteroids have been the most commonly used class of medication for induction of remission in Crohn's disease (CD). Corticosteroids down regulate production of inflammatory cytokines and interfere with NF-kappaB production, thereby blunting inflammatory response. The primary objective was to systematically review the efficacy and safety of traditional corticosteroids (given orally or intravenously) for induction of remission in CD. The following electronic databases were searched: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders (IBD/FBD) Group Specialized Trial Register, and ClinicalTrials.gov. No language restrictions were applied. Reference lists of trials and review articles, as well as recent proceedings from major gastroenterology meetings were manually searched. Randomized, controlled clinical trials of traditional, systemic corticosteroids for the induction of remission of active CD were included in this review. Control groups included patients receiving either placebo or 5-aminosalicylates (5-ASA). The study population included patients of any age with active CD (as defined by the study authors or validated clinical activity indices), receiving any formulation of systemically available corticosteroid by any oral or parenteral methods of delivery. The primary outcome was induction of remission of CD. Secondary outcomes included clinical response, change in mean CDAI, adverse events and the proportion of patients withdrawing due to adverse events. Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad's criteria. A random or fixed effects model was chosen based on an assessment of heterogeneity, and studies were weighted using the DerSimonian & Laird or the Mantel-Haenszel method accordingly. Meta-analysis was performed using RevMan 4.2.10 software. Two studies compared corticosteroids to placebo and six studies compared corticosteroids to 5-ASA. Corticosteroids were found to be significantly more effective than placebo at inducing remission in CD (RR 1.99; 95% CI 1.51 to 2.64; P < 0.00001). Corticosteroids were found to be more effective than 5-ASA at inducing remission in studies with long follow-up duration (i.e. > 15 weeks; RR 1.65; 95% CI 1.33 to 2.03; P < 0.00001). Corticosteroids induced adverse events in a higher proportion of patients than placebo (RR 4.89; 95% CI 1.98 to 12.07; P = 0.0006), or low-dose 5-ASA (RR 2.38; 95% CI 1.34 to 4.25; P = 0.003). No difference existed in the proportion of patients experiencing adverse events when steroids were compared to high-dose 5-ASA. Steroids did not induce more study withdrawals due to adverse events than either placebo or 5-ASA. Corticosteroids are effective for induction of remission in patients with CD, particularly when used for more than 15 weeks. Although corticosteroids cause more adverse events than either placebo or low-dose 5-ASA, these adverse events did not lead to increased study withdrawal in the included studies. Further information is required to determine the optimal duration of treatment and tapering protocol to maximize the efficacy of treatment with corticosteroids. Additionally, further study is required to determine whether corticosteroids are more effective in patients with certain phenotypes or when administered intravenously.

Traditional corticosteroidsfor induction of remission in Crohn disease

Traditional corticosteroidsfor induction of remission in Crohn disease

Traditional corticosteroids for induction of remission in Crohn disease: a systematic review and meta-analysis

Historically, despite common adverse effects, corticosteroids have been the most commonly used class of medication to induce clinical remission in Crohn's disease (CD). They downregulate production of inflammatory cytokines and interfere with NF-κB production, thereby blunting inflammatory response. This review and meta-analysis examined the efficacy and toxicity of corticosteroids in induction of remission in CD. The following electronic databases were searched: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trial Register, and ClinicalTrials.gov. Reference lists of trials and review articles, as well as recent proceedings from major gastroenterology meetings were manually searched. Randomized, controlled clinical trials of traditional, systemic corticosteroids for the induction of remission of active CD were included in this review. Control groups included patients receiving either placebo or 5-aminosalicylates (5-ASA). The study population included patients of any age with active CD (as defined by the study authors or validated clinical activity indices), receiving any formulation of traditional corticosteroid orally or parenterals. The primary outcome was induction of clinical remission of CD. Secondary outcomes were change in mean CDAI, adverse effects of the medications and withdrawal from the study due to adverse effects or drug intolerance. Two independent investigators reviewed studies for eligibility, and extracted the data. For the meta-analysis, a random or fixed effects model was chosen based on an assessment of heterogeneity, and studies were weighted using the DerSimonian & Laird or the Mantel-Haenszel method accordingly. Two studies compared corticosteroids to placebo and six studies compared corticosteroids to 5-ASA. When induction of clinical remission was assessed >15 weeks from start of treatment, corticosteroids proved more effective than placebo (RR 1.99, 95% CI 1.51 to 2.64, p < 0.00001) and than 5-ASA (RR 1.65, 95% CI 1.33 to 2.03, p < 0.00001). When likelihood of clinical remission was assessed earlier (at 4-6 weeks and at 10-12 weeks) corticosteroids were not found to be more effective than 5-ASA. Corticosteroids induced side effects in a higher proportion of patients compared to both placebo (RR 4.89, 95% CI 1.98 to 12.07, p = 0.0006), and to low-dose 5-ASA (RR 2.38, 95% CI 1.34 to 4.25, p = 0.003). No difference existed in the proportion of patients experiencing side effects comparing steroids to high-dose 5-ASA, nor did steroids induce more study withdrawals due to drug intolerance or adverse effects than either placebo or 5-ASA. Corticosteroids are effective at inducing remission in patients with CD, when used for more than 15 weeks with dosage taper. Although corticosteroids cause more side effects than either placebo or low-dose 5-ASA, these adverse effects did not lead to increased study withdrawals.

Oral corticosteroids for induction of remission in ulcerative colitis

Oral corticosteroids for induction of remission in ulcerative colitis

Interventions for growth failure in childhood Crohn's disease.

Crohn's disease in childhood is a chronic relapsing condition. Fifteen to forty per cent of children with Crohn's disease have growth retardation (Griffiths 1993a). Some treatment modalities including corticosteroids have been implicated in growth failure but it is thought mainly to be secondary to uncontrolled disease activity (Motil 1993; Markowitz 1993). Growth is fundamental to the practice of pediatrics, so by taking growth as the primary outcome measure we address issues important to both patients, their families and pediatricians. To evaluate the effectiveness of the different modalities available for the treatment of childhood Crohn's disease with regard to the reversal of growth failure and the promotion of normal growth. Searches were made of the following databases using the Collaborative Review Group Search Strategy: EMBASE (1984-2004), MEDLINE (1966-2004), The Cochrane Central Register of Controlled Trials, The Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register and the Science Citation Index. Abstracts from the major gastrointestinal research meetings and references from published articles were also reviewed. Randomized controlled trials pertaining to children less than 18 years of age with Crohn's disease were selected. Those with growth as an outcome measure were included in the review. Data extraction and assessment of the methodological quality of each trial was independently reviewed by two reviewers. Only one good quality randomized controlled trial was included in the review and therefore no statistical analysis was possible. Three randomized controlled trials were identified. One was of good methodological quality (Markowitz 2000). This study looked at the use of 6-mercaptopurine (6-MP) as a steroid sparing agent. No difference in linear growth was observed between the intervention and placebo groups, although the total steroid dose received over the 18 month follow up period was reduced in the group receiving 6-MP. The two remaining randomized controlled trials (Sanderson 1987; Thomas 1993a) consider the use of enteral feeding versus corticosteroids for induction of remission, with height velocity standard deviation score at 6 months as an outcome measure. Although of less rigorous methodological quality, the results of these studies are discussed in detail in the review. In both studies height velocity standard deviation scores were significantly increased in the enteral feeding group compared with the corticosteroid group. In addition to these randomized controlled trials, a body of lower quality evidence does exist relevant to two other important interventions; the use of supplemental enteral nutrition (Morin 1980; Belli 1988; Israel 1995) and the judicious use of surgical interventions in pre-pubertal children with refractory disease (Alperstein 1985; Lipson 1990; McLain 1990). Newer treatments, such as infliximab, are now becoming more widely used and may offer advantages in promoting growth. These effects are as yet unstudied. This review highlights the need for large, multi centre studies of the different treatment options in paediatric Crohn's disease and the importance of standardised measurements of growth, such as height velocity standard deviation scores and height standard deviation scores as outcome measures.

Rectal corticosteroids for induction of remission in ulcerative colitis

Rectal corticosteroids for induction of remission in ulcerative colitis