Hospital admission for IV steroids to treat UCOral corticosteroids remain the mainstay of treatment for moderately active ulcerative colitis UC. In patients who fail to respond to oral corticosteroids, attempting the intravenous route before starting rescue therapies is an alternative, although no evidence supports this strategy. To evaluate clinical outcomes after a course of intravenous corticosteroids for moderate attacks of UC according to the failed oral corticosteroids or not. All ulceratice of active UC admitted to three university hospitals boost testosterone naturally bodybuilding January and December were identified and retrospectively reviewed. Only moderately active episodes treated with intravenous corticosteroids were intravenous steroids for ulcerative colitis.
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Oral corticosteroids remain the mainstay of treatment for moderately active ulcerative colitis UC. In patients who fail to respond to oral corticosteroids, attempting the intravenous route before starting rescue therapies is an alternative, although no evidence supports this strategy.
To evaluate clinical outcomes after a course of intravenous corticosteroids for moderate attacks of UC according to the failed oral corticosteroids or not. All episodes of active UC admitted to three university hospitals between January and December were identified and retrospectively reviewed.
Only moderately active episodes treated with intravenous corticosteroids were included. Treatment outcome was compared between episodes which failed to outpatient oral corticosteroids for the index flare and those directly treated by intravenous corticosteroids. Intravenous corticosteroids are efficient for inducing remission in moderately active UC unresponsive to oral corticosteroids, but almost half of these patients develop early steroid-dependency.
Alternative therapeutic strategies should be assessed in this clinical setting. Ulcerative colitis UC is a chronic inflammatory condition of the colon that usually follows a relapsing-remitting course 1.
Within 5 years of diagnosis, most patients will have experienced several relapses regardless of disease extent, as reported in the recent population-based studies assessing the natural history of the disease 2. Medical therapy of acute UC flares depends mainly on their severity. To optimize clinical outcomes in these patients, response to any treatment should be assessed in a timely manner; in this sense, it is widely accepted that response to aminosalicylates should be evaluated in 2 to 4 weeks, whereas response to intravenous CS in severe attacks should be assessed in 3 to 5 days 4.
The approach to moderate flares is not so clear. Although oral aminosalicylates are also considered as the treatment of choice in this clinical setting 3 , many patients use these agents for maintenance treatment, and dose escalation in this situation has been poorly evaluated. An accepted alternative in these patients and in those not responding to oral aminosalicylates is oral CS therapy 3. The use of oral CS in moderately active UC is supported by the early British trials 5 — 7 , carried out in small samples and more than 60 years ago.
We now know that almost half of UC patients will require at least one course of CS in their lives mainly for moderate flares , and that this has not changed in the last six decades 2. We also know that CS requirements do not depend on the time from disease diagnosis or disease extent, and that the yearly proportion of patients treated with CS remains stable over time in a given UC cohort 8.
Unlike in mild and severe flares, there is no established timing for the assessment of response to oral CS 4 , although prospective data suggest that it can be predicted as simply and early as in severe flares 9. Despite the widespread use of oral CS in clinical practice, few RCTs including conventional oral CS for the treatment of moderately active UC have been performed 10 , Current recommendations advise initiation of anti-TNF agents, although tacrolimus or intravenous CSs are also considered potential alternatives to colectomy 3.
The aim of our study was to evaluate the utility of intravenous CS in patients who failed to respond to oral CS for a moderate flare of UC. Between January and December , all patients admitted for UC flares who received intravenous corticosteroids CSs were identified from the electronic records of three referral university hospitals. Patients were only included in the study if they had moderately active UC according to the Montreal classification of severity 12 at the time intravenous CSs were started, and patients with ulcerative proctitis were excluded.
Episodes of patients with more than one episode were only included if they did not meet steroid-dependency criteria defined by a clinical relapse during corticosteroid therapy or within the first 3 months after corticosteroid discontinuation.
Patients were grouped according to whether they had received oral prednisone for the same flare before admission. In the case of clinical response, CS tapering was started at discharge and the dose was reduced by 10 mg weekly until reaching 20 mg, and by 5 mg weekly thereafter until complete withdrawal. For the purposes of this study, we arbitrarily defined initial efficacy as mild activity or inactive disease according to the Montreal severity score, with no need for rescue treatment at day 7 after starting intravenous CS.
Patients were followed up until colectomy, death, or date of data collection September , and the occurrence of steroid-dependency criteria or colectomy during follow-up was also recorded. For each episode, every outcome was addressed until the end of follow-up, death or the occurrence of a new flare requiring corticosteroids. All statistical analyses were performed using SPSS Data are expressed as median and interquartile range IQR or absolute and relative frequencies.
Chi-square was used to compare dichotomous variables. Otherwise, Mann—Whitney U-test was used. Predictive factors of initial efficacy, colectomy, and steroid-dependency were initially univariately screened with the above-mentioned tests.
A total of episodes of intravenous CS therapy in patients with UC were recorded during the study period. Among these, episodes in 89 patients corresponded to moderate flares. No differences were found between patients who were directly treated with intravenous CS for a moderate flare and those who failed to oral CS for the index flare, except for a higher proportion of previous courses of systemic CS, a younger age, a higher proportion of maintenance therapy with mesalazine before the index flare but the same on thiopurines , and lower C-reactive protein levels among the latter Table 1.
Characteristics of episodes according to failed oral corticosteroids for the index flare or directly treatment with intravenous corticosteroids. Data expressed as absolute and relative frequencies and median interquartile range.
According to the Montreal classification of severity, all episodes had moderate activity at the onset of intravenous CS. Both study groups also had similar median levels of C-reactive protein at day 3 14 [3—61] vs.
We found no baseline factor associated with initial efficacy, and only those patients with a lesser disease activity at day 3 of intravenous CS therapy had a higher probability to achieve initial efficacy criteria Table 2. Three episodes required colectomy during hospital admission after a median time of 28 days from the beginning of intravenous CS IQR 20— Proportion of episodes achieving mild activity or inactive disease at day 3 or 7 of intravenous corticosteroids, stratified by failure of oral corticosteroids black bars or directly treatment with intravenous corticosteroids grey bars for the index flare.
Associated factors to initial efficacy. No differences regarding the incidence of short-term CS-related major side effects were found between the study groups. Seven episodes required insulin therapy during CS therapy and infections developed in nine episodes. One patient died because of an infectious complication. She was a year-old former smoker with distal UC who initially received intravenous UC for a moderate flare. She had a clinical response and CSs were discontinued 56 days later.
Two months after CS withdrawal, she died of acute pneumonia. Finally, 11 patients were colectomized after a median of 7 months from the index flare IQR 4—17 , but no associated factor was found on both the univariate and logistic regression analyses.
One patient died during follow-up. He was a year-old former smoker with longstanding distal UC who achieved response to intravenous CS, which could be successfully withdrawn. The patient relapsed 10 months later and was colectomized. He died of multiple non-infectious postoperative complications.
Outcomes during follow-up, stratified by failure of oral corticosteroids black bars or directly treatment with intravenous corticosteroids grey bars for the index flare. Associated factors to development of steroid-dependency during follow-up. Oral CSs are frequently used in UC. As mentioned before, oral prednisolone produces clinical remission at 4 weeks in about two-thirds of patients with moderate UC flares.
Although the oral route is recommended for moderate flares, intravenous administration is not unusual in clinical practice. Despite this, both routes of administration have never been compared in this clinical setting. No advantages of the intramuscular route were demonstrated, and clinical response was actually faster among patients treated via the oral route Therefore, at least one-third of the patients with moderately active UC treated with oral CS perhaps more if response to therapy is assessed within the first 3—5 days are potential candidates for treatment escalation.
Few alternatives to colectomy are available in this clinical scenario, and none has been specifically assessed in the controlled trials. It has also been repeatedly advised that the intravenous route should be attempted in this setting, although there is no clinical evidence to support this recommendation 3 , From a pharmacokinetic point of view, two studies carried out in the s in patients with severe UC reported that prednisolone absorption was delayed as compared with the healthy controls when administered orally 17 , When given intravenously, no difference was found between patients and controls.
In UC patients, plasma levels were persistently higher during the 8-hour study period after 20 mg given intravenously as a bolus or in continuous infusion vs. These findings led the authors to recommend the intravenous route, at least in severe attacks. From this perspective, trialling intravenous CS therapy is a particularly sound option in patients with poor or partial response to oral CS. Remission as defined by the resolution of symptoms together with a normal endoscopic appearance at sigmoidoscopy was achieved in However, this series is hardly comparable to ours as far as remission was not defined by means of time, and long-term outcomes were clearly influenced by the lack of maintenance therapy other than sulfasalazine or the prophylactic use of colectomy in long-lasting UC.
No clear rules are established for decision-making in moderate flares and even less after failure of oral CS , which is why we arbitrarily decided to use mild or inactive disease and no need for rescue therapy at day 7 of intravenous CS as the main efficacy endpoint.
This finding should stimulate the use of the intravenous route instead of calcineurin inhibitors or anti-TNF agents in patients failing to respond to oral CS. Disappointingly, the present investigation does not provide useful tools to improve treatment strategies in this clinical scenario. This is mainly due to the limitations of the study. First, due to its retrospective design, we cannot account for a propensity to use the intravenous route in patients previously treated or not previously treated with oral CS.
Second, we did not assess endoscopic findings, and endoscopic remission has demonstrated to be of outstanding relevance to predict better outcomes in patients with clinical response Moreover, faecal calprotectin levels were not available in our centres at the time of the study. The availability of serial faecal markers and endoscopic findings among patients with initial clinical response might have helped conceive an improved treatment algorithm in this clinical setting.
Therefore, prospective controlled trials comparing oral and intravenous CS for the treatment of moderate flares of UC are warranted. In summary, intravenous CSs are highly efficient in inducing clinical response in moderate UC flares, particularly when compared to the reported efficacy of oral CS in RCTs. In patients failing oral CS, attempting intravenous CS may be considered an alternative, with good initial efficacy but a high likelihood of early steroid-dependency.
Therefore, in patients with moderate flares, intravenous CS should be evaluated as a first-line treatment. Otherwise, in patients who failed to respond to oral CS, this strategy should be compared to other medical options such as calcineurin inhibitors and anti-TNF agents, particularly with respect to long-term outcomes. Naves designed the study, collected and analysed the data, and wrote the paper.
All authors approved the final version of the article, including the authorship list. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
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