Degree project, 30 ECTS [2019-06-12]
The comparative efficacy of biologics in patients
with Crohn´s disease and Ulcerative Colitis
Version 2
Author: Elan Adel Khalaf, MB
School of Medical Sciences Örebro University Örebro Sweden
Supervisor: Daniel Sjöberg, MD PhD
Centre for Clinical Research Falu Hospital Falun Sweden Word count Abstract: [247] Manuscript: [2839]
Abstract
Introduction
The fundamental concept for modern inflammatory bowel disease (IBD) treatment algorithm is an early induction of mucosal healing and its maintenance. Biological therapies are
becoming mainstays of IBD therapy. It is however still unclear if there is a difference between Crohn’s disease (CD) and Ulcerative Colitis (UC) in time from diagnosis to stable maintenance treatment when biological treatment is introduced.
Aim
To investigate the comparative efficacy of biological agents in CD and UC by studying the time course when biological treatment is introduced.
Methods
Retrospective study of patients suffering from IBD at Falu Hospital, receiving a new start with biologics between 2015-01-01 and 2016-12-31. Remission rate after 3 months of
induction therapy was analyzed. Subsequently, when 6 months passed without active disease, it was considered a stable remission.
Results
Through database extraction 58 patients were identified. A total of 52 % patients fulfilled the criteria for remission. Of patients with CD 49 % got in remission, whereof 33 % had
treatment with infliximab, 48 % adalimumab and 19 % vedolizumab. Of patients with UC 60 % got in remission, whereof 33 % had treatment with infliximab and 67 % with adalimumab. Log rank test showed no significant difference in efficacy of biologics in patients suffering from CD or UC in time from diagnosis respective after initiation with biologics to stable maintenance treatment.
Conclusions
In this study patients with CD and UC responded equally to biological treatment.
Key words
Abbreviations
5-ASA 5-aminosalicylic acid
ADA Adalimumab
CC Collagenous Colitis
CD Crohn´s disease
GI Gastrointestinal
IBD Inflammatory Bowel Disease
ICD International Classification of Diseases
IFX Infliximab
IQR Interquartile range
TNF-α Tumor necrosis factor- alpha UC Ulcerative colitis
Introduction
Inflammatory Bowel Disease (IBD) is a group of inflammatory diseases characterized by progressive chronic and relapsing inflammation of the gastrointestinal (GI) tract [1,2]. IBD affects people in their most productive period of life [3]. The two main diseases within this group include Crohn´s disease (CD) and Ulcerative Colitis (UC). The inflammation site in CD can be in every part of the GI tract unlike UC where the inflammation is mainly limited to the rectal and colonic mucosa [1,2]. The progression of the inflammation over time results in irreversible mucosal damage, disability and increases the incidence of colitis-associated neoplasia [4–6]. Consequently, this leads to high costs to the medical system [7–10].
There is no internationally accepted gold standard scoring system or criteria for the diagnosis of IBD. Therefore, the diagnosis is based on clinical and laboratory findings in combination of endoscopic, histological and radiological changes [1,2]. Also the etiopathology is not fully understood but it is generally accepted that the inflammation is caused from a multifactorial process involving a stimulation of a dysfunctional immune system by a trigger in the
environment in a genetically predisposed individual [11–13]. Accumulating evidence suggest that an overexpression of proinflammatory cytokines, especially tumor necrosis factor-α (TNF-α), is the central mediation of systemic inflammation [14,15].
The most potent medical therapies for IBD are currently the biologics [9]. They are
monoclonal antibodies with an activity directed against specific critical targets involved in the inflammatory pathway, allowing selective but highly potent regulation of the
inflammation [7,16]. The anti-TNF-α agents are often first-line biologics but the biologic agent selected for treatment is depending on financial considerations and patient-specific factors [7,17].
The biologics are effective for both induction and maintenance therapy [18]. The treatment results in nearly 40 % remission rates at one year [19]. A randomized, double-blind trial demonstrated that corticosteroid-free clinical remission rate in patients with CD who were treated with infliximab monotherapy or infliximab in combination with azathioprine was significantly higher compared to patients who received azathioprine monotherapy [20]. The risk of infections is the most important safety concern [21,22]. Another common adverse effect is increased risk of malignancy but the potential risk for serious infections and
malignancies is relatively low in younger patients without co-existing medical conditions [23,24].
Even if biological therapies are becoming mainstays of IBD therapy, their efficacy to alter disease course has not been clearly defined. Prior studies have reported that treatment with biologics are more effective when initiated early in the disease course. In a post-hoc analyses of the CHARM trial of adalimumab in CD a shorter disease duration was identified as a significant predictor for higher remission rate. The remission rate at week 56 was
significantly greater among patients receiving adalimumab early after diagnosis (43% for<2 years; 30% for 2 to <5 years; 28% for ≥5 years) [25]. A post-hoc analyses of the PRECISE 2 trial of certolizumab in CD demonstrated similar findings. At week 26, 82 % of patients with a disease duration less than two years had a response, compared with 59 % among patients with a disease duration longer than two years. In the placebo subgroups the response and remission rate did not differ significantly by disease duration [26].
In contrast to the growing literature on the advantages of early intervention in CD with biologics, the early intervention with biologics in UC is vague. Consequently, we performed this study in purpose to investigate if there is a difference between CD and UC in time from diagnosis to stable remission among patients treated with biologics at the county hospital of Falun. Since patients with UC have the advantage of efficient treatment with 5-ASA, our hypothesis is that patients with CD will receive remission later in the disease course in comparison with patients with UC.
Aim
The aim for this trial was to investigate the comparative efficacy of biologics in patients with CD and UC by studying the time course when biological treatment is introduced.
Material and Methods
Study design
This is a retrospective cohort study where patients were included consecutively.
Participants
Patients were included in the study if they met the following criteria: a confirmed diagnosis of CD or UC based on ICD coding at the Department of Internal Medicine, Falu Hospital, Sweden, who received initiation with biological agents between 2015-01-01 and 2016-12-31. The biological agents of interest were infliximab (Remicade®/Remsima®), adalimumbab
were excluded. Participants were followed until 2019-01-31. The collection of data was made between February 2019 and March 2019.
Variables
Data on variables of relevance were collected including patients characteristics (age, gender, diagnosis, date of diagnosis), disease characteristics (disease phenotype classified according to the Montreal classification) and treatment history (date of initiation with biologic agents; duration of use; indication for discontinuation).
Outcome
The primary outcome was time from diagnosis to stable maintenance treatment with biologics. Secondary outcome was time from start with biological treatment to stable remission. The clinical response and remission rate after 3 months of first-time exposure to biologics in patients suffering from IBD was analyzed. After the follow-up visit the medical records were investigated in order to determine the date where the patients fulfilled the criteria for remission. Hence when 6 months passed without active disease, it was considered a stable remission.
There is no internationally accepted definition of remission, therefore we used the clinical definition which is: 1) lack of dose escalation; 2) absence of systemic steroid treatment; and 3) absence of symptoms ((≥ 4 diarrhea/day, active inflammation on endoscopy, blood in the stool, calprotectin ≥400 mg/kg). We defined dose escalation as: 1) increase of adalimumab from 40 mg every other week to 80 mg every other week or 40 mg weekly; 2) doubling dose infliximab compared to starting dose or adjusting the interval between the infusions from 8 weeks to 4 weeks; or 3) adjusting the interval for vedolizumab from 8 weeks to 4 weeks. Systemic steroid therapy included treatment with prednisolone or betamethasone
continuously. Oral budesonide or rectal steroid treatments were not considered.
Statistical analysis
All data analyses in the study were performed using the statistical software IBM SPSS Statistics 25. Data collection was performed in Microsoft Excel 2016 from the medical records system TakeCare. Continuous variables are presented as median and interquartile range (IQR). The difference between groups were evaluated using Chi-Square test in regard of gender and biologic agent. Mann-Whitney U test was used for evaluating the difference between groups regarding age and disease duration. Plots of patients with CD and UC introduced to biological agents were constructed using Kaplan-Meier analysis and log-rank tests. P-values < 0.05 were considered statistically significant. All tests were 2-sided.
Ethical considerations
This study was classified as a regular activity monitoring at the clinic and accordingly no approval from the Ethics Committee was required. Since the study was retrospective and therefor did not cause any inconvenience to the patient in form of additional return visits or intervention no consent was needed from the patients. The study was conducted with
professional confidentiality as well as deidentification and had approval from the operations manager at the medical clinic at the hospital in Falun. The patient lists with identification numbers have been restricted to the author of the thesis and supervisor. Only data relevant to the study was presented aggregated to avoid individual patients to be recognized. The journal review entailed a certain intrusion into the integrity, but we believed that the benefits was greater than the risks, as this study can contribute to optimization of future patients’ drug treatment.
Results
Patients
A total of 116 patients were identified by database through the medical chart TakeCare during the inclusion period when stratified by introduction to medical treatment with biologics. After duplicates had been removed from the patient list a total of 109 patients remained. Fifty-one patients did not fulfil the criteria for the study and were excluded. One of the patients excluded did not have CD or UC but Collagenous Colitis (CC). The main reason however for the patients excluded from the study was being exposed to the biological agent in question before the date 2015-01-01.
The Table 1 summarizes the baseline demographics including disease phenotype according to Montreal classification and the pharmaceutical biological agents the patients received during the inclusion period. The median age of the whole study population was 39.0 (28.0-56.8). Patients with CD were 11 years younger than patients with UC (median age 38.0 vs 49.0). In this study the population composed of more patients with CD than UC at a ratio of 3:1. A total of 51.7 % (n=30) of the study population were women and 48.3 % (n=28) men. The median years of disease duration, which is the date of diagnosis till the day 2019-01-31 for the whole population was 7,7 years (4.8-13.9).
There was no statistically significant difference between the two groups regarding age, gender, disease duration and treatment with biologics.
Table 1. Demography and medication. Crohn´s disease (n=43) Ulcerative Colitis (n=15) P-value
Median age, years (IQR) 38 (28-53) 49 (27-60) 0.46
Gender, women, n (%) 24 (56) 6 (40) 0.29
Gender, men, n (%) 19 (44) 9 (60) 0.29
Extent, n (%) Proctitis (E1) 2 (13)
Left sided colitis (E2) 0 (0) Extensive (E3) 13 (87) Location Ileal (L1) 18 (42) Colonic (L2) 23 (53) Ileocolonic (L3) 2 (5) Disease duration, median years (IQR)
8.8 (5.0-14) 5.4 (4.4-13) 0,19
Treatment Infliximab, n 23 12 0.07
Adalimumab, n 27 11 0.46
Vedolizumab, n 10 2 0.41
Medical treatment
Figure 1 presents the use of pharmaceutical therapy in each patient included in the study after
diagnosis. The figure shows that patients diagnosed recently with IBD are more likely receive treatment with biologics early in the disease course. With treatment with biologics a total of 51.7 % (n=30, (n=21 CD; n=7 UC)) patients fulfilled the criteria for remission. Of patients with CD 49 % got in remission, whereof 33 % (n=7) had treatment with infliximab, 48 % (n=10) adalimumab and 19 % (n=4) vedolizumab. Of patients with UC 60 % got in remission, whereof 33 % (n=3) had treatment with infliximab and 67 % (n=6) with adalimumab.
Thirty-five patients were introduced to infliximab during the inclusion period. Eleven patients (8 CD; 3 UC) had ongoing treatment with infliximab at the end of the study. Of the 24 patients who no longer received infliximab five patients experienced side effects, eleven patients had no therapeutic effect and one patient ended the treatment due to long-term
remission. The reason for the remaining seven patients not receiving therapy with infliximab was either unclear or due to other disorders/factors.
A total of 38 patients were exposed to adalimumab. Eighteen patients (11 CD; 7 UC) had ongoing treatment. Of the 20 patients who stopped treatment with adalimumab eight patients experienced side effects, eight patients had no therapeutic effect and one patient had long-term remission. The reason for the remaining two patients not receiving adalimumab was either unclear or due to other factors/disorders. In one patient the treatment was stopped due to non-compliance.
Twelve patients were treated with vedolizumab during the inclusion period. Six patients had ongoing treatment at the end of the study and all of them suffered from CD. Among the six patients who no longer received adalimumab one experienced side effects, four patients had no therapeutic effect and one patient stopped due to an unclear reason.
The hypothesis test by log rank test and Kaplan-Meier plots did not show a significant difference in remission rate in patients suffering from CD and UC in time from diagnosis to stable maintenance treatment respective after introduction to biologics (Figure 2 and 3). Multivariate analysis was not performed due to the small sample size.
Figure 2. Kaplan-Meier plot of patients with CD and UC showing time after diagnosis to stable remission. Log
Figure 3. Kaplan-Meier plot showing time from start with biological treatment to stable remission in patients
with CD and UC. Log rank test not significant (p-value=0.24).
Discussion and Conclusions
An association between disease duration and maintenance of clinical remission or response derived from initiating biologic therapy in patients with IBD has been identified in other studies. To the best of our knowledge this is the first study investigating the comparative efficacy of biologics in patients in CD and UC by studying the time course when initiating biologic therapy. Previous similar studies are based on either CD or UC, not both diagnoses in the same study. Our study result is consistent with these prior studies in showing the efficacy of biologics in treatment for IBD.
CD and UC are progressive conditions, causing disease complications, high morbidity, impaired quality of life in a relatively young patient population and high costs to the medical system due to the chronic inflammation [1–3,7–9]. The growing availability of effective biological therapies has been revolutionary in IBD care. Patients diagnosed recently with IBD are more likely to receive treatment with biologics early in the disease course that conform with our study result.
Based on previous studies biologics and in particular anti-TNF antibodies lead to a
when initiated in the first two years after diagnosis of IBD. A systematic review demonstrated that anti-TNF biologics reduced the odds of hospitalization by 50 % and surgery by 33-77 % in both CD and UC when comparing three biologics and one
immunomodulator with placebo in a total of seven randomized controlled trials (5 CD; 2 UC) [27].
In a multicenter consortium study similar finding have been found regarding on early intervention in CD with vedolizumab. Within 6 months introduction of treatment with vedolizumab a significant higher proportion of patients with early-stage CD (≤2 years duration), vs later-stage CD (>2 years duration) achieved clinical remission (38 % vs 23 %), corticosteroid-free remission (43 % vs 14 %), and endoscopic remission (29 % vs 13 %). In contrast, the result in that study did not show a beneficial correlation between UC and early TNF antagonist medications. There were no significant differences in outcomes between early and longer disease duration groups [28].
Several studies with similar findings are published. Mandel et al found no significant decrease in hospitalization rate in UC after initiation of TNF antagonist therapy within 3 years from diagnosis as opposed to CD. In CD the hospitalization rate decreased significantly and there was a trend towards a decreased need for surgical intervention with anti-TNF exposure during median 2 years, although the latter was not statistically significant. They also reported a difference between early and late initiation of anti-TNF exposure. When initiation of anti-TNF agents within 3 years from diagnosis the need for hospitalization decreased significantly[29].
At present it is unclear why the response of patients with CD and UC to biologics differs, stratified by disease duration. However, the growing literature on this topic however
accumulating demonstrates improved outcomes with early intervention of biologics in CD. In UC the benefits of early intervention are to date uncertain.
To the extent of our knowledge this is the first trail to study the time course when biological treatment is introduced with effect on the intestinal inflammation in patient with Chron´s disease and Ulcerative Colitis in the same study. Yet due to limits in time the study
population was too small and thereby the study was underpowered. Further limitations of the present analysis include that is was retrospective and patients were not randomized on the basis of disease duration. In addition, we could not examine the effects of biologics
depending on disease phenotype, biochemical or genetic predictors of response or failure and previous treatment experience with concomitant IBD-related medications due to the small sample size. The study can however be used as a pilot study for further research on this topic. Also, since the aetiology of IBD is unknown and probably multifactorial more variables and factors such as comorbidities, other medications, surgery, socioeconomic factors should be considered. There is an urgent need for future similar, preferably prospective and randomized controlled, studies in order to optimize and individualize the therapy for these complex and progressively disabling diseases.
In conclusion, this retrospective study could not state a significant difference in efficacy of biologics in patients suffering from CD or UC in time from diagnosis to stable maintenance treatment. Neither was a difference found in remission rate after introductions with biologics between the two groups.
Acknowledgment
First and foremost, I would like to express my special gratitude and thanks to my supervisor, Dr Daniel Sjöberg, for his constant fruitful guidance, support as well as for providing
necessary information and directions throughout the project. Thank you for being the best supervisor possible! Ever since the start of this project you have always been supportive and convenient. For that I am very grateful. I also thank all the health personnel at the
Department of Gastroenterology, Falu hospital, for welcoming me and helping me in carrying out this project.
Furthermore, I would like to pay tribute to my friends for your support and encouragement. Finally, I would like to express my deepest appreciation to my family for you love, support and belief in me.
References
1. Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohns Colitis.
2016;11(1):3–25.
2. Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, et al. Third European evidence-based consensus on diagnosis and management of
pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis. 2017;11(6):649–70.
3. Sairenji T, Collins KL, Evans DV. An Update on Inflammatory Bowel Disease. Prim Care Clin Off Pract. 2017 Dec 1;44(4):673–92.
4. Atreya R, Neurath MF. Current and future targets for mucosal healing in inflammatory bowel disease. Visc Med. 2017;33(1):82–8.
5. Neumann H, Neurath MF, Mudter J. New endoscopic approaches in IBD. World J Gastroenterol WJG. 2011 Jan 7;17(1):63–8.
6. Pariente B, Cosnes J, Danese S, Sandborn WJ, Lewin M, Fletcher JG, et al. Development of the Crohn’s disease digestive damage score, the Lemann score. Inflamm Bowel Dis. 2010;17(6):1415–1422.
7. Guno TH, Simadibrata M. The Role of Biologics Agent in the Treatment of
Inflammatory Bowel Disease. Indones J Gastroenterol Hepatol Dig Endosc. 2018 Mar 5;18(3):184–96.
8. Yu AP, Cabanilla LA, Wu EQ, Mulani PM, Chao J. The costs of Crohn’s disease in the United States and other Western countries: a systematic review. Curr Med Res Opin. 2008 Feb 1;24(2):319–28.
9. Cohen RD, Yu AP, Wu EQ, Xie J, Mulani PM, Chao J. Systematic review: the costs of ulcerative colitis in Western countries. Aliment Pharmacol Ther. 2010;31(7):693–707. 10. Ramos GP, Papadakis KA. Mechanisms of Disease: Inflammatory Bowel Diseases.
Mayo Clin Proc. 2019 Jan 1;94(1):155–65.
11. Paramsothy S, Rosenstein AK, Mehandru S, Colombel J-F. The current state of the art for biological therapies and new small molecules in inflammatory bowel disease. Mucosal Immunol. 2018;1.
12. Cargiolli M, Miranda A, Bottiglieri ME. Inflammatory bowel disease: gender difference. Ital J Gend-Specif Med. 2017 Jan 1;3(1):23–8.
13. Bamias G, Nyce MR, De La Rue SA, Cominelli F. New Concepts in the Pathophysiology of Inflammatory Bowel Disease. Ann Intern Med. 2005 Dec 20;143(12):895.
14. Braegger C p., Nicholls S. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet. 1992 Jan 11;339(8785):89.
15. Tumour necrosis factor‐alpha and interferon‐gamma production measured at the single cell level in normal and inflamed human intestine - MACDONALD - 1990 - Clinical & Experimental Immunology - Wiley Online Library [Internet]. [cited 2019 Apr 14]. Available from:
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2249.1990.tb03334.x
16. Cohen LB, Nanau RM, Delzor F, Neuman MG. Biologic therapies in inflammatory bowel disease. Transl Res. 2014 Jun 1;163(6):533–56.
17. Danese S, Vuitton L, Peyrin-Biroulet L. Biologic agents for IBD: practical insights. Nat Rev Gastroenterol Hepatol. 2015 Sep;12(9):537–45.
18. Denmark V. Safety and Immunogenicity of Biologic Therapy in Inflammatory Bowel Disease. Hosp Med Clin. 2017 Jul 1;6(3):425–35.
19. Hirten RP, Iacucci M, Shah S, Ghosh S, Colombel J-F. Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders. Clin Gastroenterol Hepatol. 2018 Sep 1;16(9):1374–84.
20. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, et al. Infliximab, Azathioprine, or Combination Therapy for Crohn’s Disease. N Engl J Med. 2010 Apr 15;362(15):1383–95.
21. Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Price S, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREATTM registry. Am J Gastroenterol. 2012 Sep;107(9):1409–22. 22. Rodríguez de Santiago E, Albillos Martínez A, López-Sanromán A. Infections in
inflammatory bowel disease. Med Clínica Engl Ed. 2017 May 10;148(9):415–23. 23. Stallmach A, Hagel S, Bruns T. Adverse effects of biologics used for treating IBD. Best
Pract Res Clin Gastroenterol. 2010 Apr 1;24(2):167–82.
24. Bonovas S, Fiorino G, Allocca M, Lytras T, Nikolopoulos GK, Peyrin-Biroulet L, et al. Biologic Therapies and Risk of Infection and Malignancy in Patients With
Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis. Clin Gastroenterol Hepatol. 2016 Oct 1;14(10):1385-1397.e10.
25. Schreiber S, Reinisch W, Colombel JF, Sandborn WJ, Hommes DW, Robinson AM, et al. Subgroup analysis of the placebo-controlled CHARM trial: Increased remission rates through 3 years for adalimumab-treated patients with early Crohn’s disease. J Crohns Colitis. 2013 Apr 1;7(3):213–21.
26. Schreiber S, Colombel J-F, Bloomfield R, Nikolaus S, Schölmerich J, Panés J, et al. Increased response and remission rates in short-duration Crohn’s disease with
subcutaneous certolizumab pegol: an analysis of PRECiSE 2 randomized maintenance trial data. Am J Gastroenterol. 2010 Jul;105(7):1574–82.
27. Mao EJ, Hazlewood GS, Kaplan GG, Peyrin‐Biroulet L, Ananthakrishnan AN. Systematic review with meta‐analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalisation and surgery in Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther. 2017;45(1):3–13.
28. Faleck DM, Winters A, Chablaney S, Shashi P, Meserve J, Weiss A, et al. Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn’s Disease But Not Ulcerative Colitis. Clin Gastroenterol Hepatol. 2019;
29. Mandel MD, Balint A, Golovics PA, Vegh Z, Mohas A, Szilagyi B, et al. Decreasing trends in hospitalizations during anti-TNF therapy are associated with time to anti-TNF therapy: Results from two referral centres. Dig Liver Dis. 2014 Nov 1;46(11):985–90.
Populärvetenskaplig sammanfattning
Inflammatorisk tarmsjukdom är ett samlingsbegrepp som innefattar flera sjukdomar som karakteriseras av kronisk inflammation i tarmslemhinnan, där Crohns sjukdom och ulcerös kolit utgör de två vanligaste. Etiologin till sjukdomarna är ofullständigt klarlagd men anses vara av multifaktoriell genes, där både genetiken och miljön har betydelse för
sjukdomsuppkomsten.
Behandlingsriktlinjerna för inflammatorisk tarmsjukdom har förändrats de sista årtiondena då biologiska läkemedel har introducerats. Den ledande aktuella behandlingsprincipen är tidigt insatt aktiv behandling för att undvika skada på tarmen, bibehålla hälsorelaterad livskvalité och minska symtombördan. Ackumulerade data från tidigare studier visar att insatt
behandling med biologiska läkemedel inom 2 år från diagnos ökar sannolikheten att behandlingen fungerar, åtminstone för Crohns sjukdom. Det är oklart om patienter med ulcerös kolit svarar på biologiska läkemedel i samma grad som patienter med Crohns sjukdom i nuläget.
Syftet med denna retrospektiva studie var att studera tidsförloppet när biologiska läkemedel sätts in under tidsperioden 2015-01-01 till och med 2016-12-31 hos patienter med Crohns sjukdom och ulcerös kolit vid magtarmmottagningen Falu lasarett. Utfallet var tid från diagnos till stabil underhållsbehandling.
Enligt vårt studieresultat föreligger det inte skillnader mellan Crohns sjukdom och ulcerös kolit i tid från diagnos till stabil underhållsbehandling. Men eftersom studiepopulationen var liten behövs ytterligare större studier med samma studieupplägg för bekräftelse.
Cover letter
Elan Adel Khalaf, MBBS Department of Gastroenterology/Hepatology Falu Hospital Falun Sweden 2019-05-27
Dear Editor of the Journal of Gastroenterology and Hepatology,
We wish to submit an original research article entitled “The comparative efficacy of biologics in patient with Crohn´s disease and Ulcerative Colitis in time from diagnosis to stable
maintenance treatment” for consideration by Journal Gastroenterology and Hepatology.
We confirm that this work is original and has not been published, nor is it currently under consideration for publication elsewhere.
In this paper, we report on the comparative efficacy of biological agents in Crohns´s disease and Ulcerative Colitis by studying the time course when biological treatment is introduced. This is significant because biological therapies are becoming mainstays of IBD therapy, but their ability to alter disease course in Crohn´s disease and Ulcerative Colitis is unclear.
We believe that this manuscript is appropriate for publication by Journal of Gastroenterology and Hepatology because it provides crucial information on optimization of therapy for IBD with biologics as well as opportunity for new research area.
We have no conflicts of interest to disclose.
Please address all correspondence concerning this manuscript to the author at elan_khalaf@outlook.com.
Thank you for your consideration of this manuscript. Sincerely,
Etiska överväganden
Denna studie klassificerades som en ordinarie verksamhetsuppföljning på kliniken och således behövdes inget godkännande av etisk kommitté. Det fanns inget behov av samtycke från patienterna som inkluderades, eftersom data endast samlades in genom
journalgenomgång och då metoden inte medförde besvär för patienterna i form av ytterligare återbesök eller intervention.
Studien har skett med sekretess samt avidentifiering och har godkännande från
verksamhetschefen på medicinkliniken vid Falu Lasarett. Tillgång till en från journalsystemet utskriven patientlista med personnummer har begränsats till författaren av studien samt handledaren. En datafil upprättades med avidentifierade löpnummer för analysarbetet.
Endast data som var relevanta för studien registrerades. Data har presenterats aggregerat och inga enskilda patienter kan identifieras i resultatet. Journalgenomgången innebär ett visst intrång i patientintegriteten, men vi bedömer att nyttan är större än riskerna då denna studie kan bidra till optimering av framtida patienters läkemedelsbehandling.
