Ludzkie koronawirusy - autor: Krzysztof Pyrć z Zakładu Mikrobiologii, Wydział Biochemii, Biofizyki i Biotechnologii, Uniwersytet Jagielloński, Kraków

Zastanawiasz się, jak wydać pracę doktorską, habilitacyjną lub monografię? Chcesz dokonać zmian w stylistyce i interpunkcji tekstu naukowego? Nic prostszego! Zaufaj Wydawnictwu Borgis – wydawcy renomowanych książek i czasopism medycznych. Zapewniamy przede wszystkim profesjonalne wsparcie w przygotowaniu pracy, opracowanie dokumentacji oraz druk pracy doktorskiej, magisterskiej, habilitacyjnej. Dzięki nam nie będziesz musiał zajmować się projektowaniem okładki oraz typografią książki.

Poniżej zamieściliśmy fragment artykułu. Informacja nt. dostępu do pełnej treści artykułu tutaj
© Borgis - Postępy Nauk Medycznych 3/2014, s. 197-201
*Anna Wiernicka, Maciej Dądalski, Monika Szychta, Grzegorz Oracz, Jarosław Kierkuś
Leczenie biologiczne wrzodziejącego zapalenia jelita grubego u dzieci
Biological therapy for pediatric ulcerative colitis
Department of Gastroenterology, Hepatology and Feeding Disorders, Children’s Memorial Health Institute, Warszawa
Head of Department: prof. Józef Ryżko, MD, PhD
Streszczenie
Wrzodziejące zapalenie jelita grubego jest przewlekłą chorobą zapalną jelit o nieznanej etiologii. Obecnie główną rolę w patogenezie przypisuje się cytokinom prozapalnym, główną z nich jest czynnik martwicy nowotworów (TNF-α). Postępy w zrozumieniu patogenezy choroby doprowadziły do wprowadzenia nowych opcji terapeutycznych, mianowicie leków biologicznych. Amerykańska Agencja Żywności i Leków (FDA) do dnia dzisiejszego zarejestrowała trzy przeciwciała monoklonalne skierowane przeciwko TNF-α do leczenia pacjentów dorosłych ze średnio ciężką i ciężką postacią wrzodziejącego zapalenia jelita grubego, którzy niedostatecznie odpowiedzieli na standardowe leczenie lub leczenie jest źle tolerowane bądź istnieją przeciwwskazania do konwencjonalnej terapii. Należą do nich infliximab, adalimumab i golimumab. Jedynie infliximab został zarejestrowany przez agencję do leczenia pacjentów pediatrycznych, pomimo to adalimumab również jest wykorzystywany w terapii u dzieci z wrzodziejącym zapaleniem jelita grubego. Celem poniższej pracy jest podsumowanie aktualnej wiedzy na temat leków biologicznych mających zastosowanie w terapii wrzodziejącego zapalenia jelita grubego u dzieci. Obecnie przeciwciała monoklonalne stanowią integralną część algorytmu leczniczego i prawdopodobnie wraz z czasem coraz częściej będą wykorzystywane w terapii.
Summary
Ulcerative colitis is a chronic inflammatory bowel disease of unknown etiology. Actually, the main pathogenic role is attributed to pro-inflammatory cytokines, the major one is Tumour Necrosis Factor alpha (TNF-α). The advances in understanding the pathogenesis of inflammatory bowel disease have led to the introduction of new therapeutic options, biological agents. Till now U.S. Food and Drug Administration (FDA) approved three monoclonal antibodies against TNF-α to treat adults with moderate to severe ulcerative colitis with an inadequate response to conventional therapy, or who are intolerant, or have medical contraindications for such therapy. These are: infliximab, adalimumab and golimumab. Only infliximab has been approved by the agency to treat children, nonetheless adalimumab is also used in treatment of pediatric patients with ulcerative colitis. The purpose of this review is to summarize the current knowledge on the use of biologics in pediatric ulcerative colitis. Currently, this new therapeutic options are the integral part of the pediatric ulcerative colitis treatment algorithm and with time probably will be used more extensively.
Ulcerative colitis (UC) is an idiopathic chronic disease associated with inflammation in gastrointestinal tract. Genetic, environmental and immunologic factors are considered to take part in the etiology. Actually, the main pathogenic role is attributed to pro-inflammatory cytokines such as TNF-α, IL-1β, IL-8, IL-12. Pediatric UC is characterized by a variable clinical course ranging from mild to severe, unresponsive to conventional therapy. Diarrhea, hemochezia and abdominal pain are the most common signs of the illness, likewise the constipation can be an early symptom (1, 2). In children compared to adult patients the distribution of disease is more extensive, most of them (over 80%) have pancolitis (1, 3). Diagnosis of the disease in the early childhood is associated with more aggressive clinical course, which is often refractory to corticosteroid treatment, requiring intensification of therapy (4-6). Treatment strategy depends mainly on disease severity. Pediatric UC treatment comprises use of corticosteroids, 5-amionosalicylates 5-ASA (mesalazine, sulfasalazine), immunomodulators: thiopurines (azatioprine AZA, mercaptopurine 6-MP), calcineurin inhibitors (ciclosporin, tacrolimus), antibiotics, probiotics and biological agents. Finally, colectomy is always a viable option that must be discussed whenever treatment escalation is considered.
The latest advances in understanding the pathogenesis of inflammatory bowel disease have led to the introduction of new therapeutic options, namely biological agents. Currently U.S. Food and Drug Administration (FDA) approved three monoclonal antibodies against pro-inflammatory cytokine Tumour Necrosis Factor alpha (TNF-α) to treat adults with moderate to severe ulcerative colitis. These are: infliximab, adalimumab and golimumab. Only infliximab has been approved by the agency to treat children 6 years and older, however, adalimumab is used out of label in pediatric patients by drawing on data from adults. The aim of this paper is to review the biologics used in the treatment of ulcerative colitis in children.
The first anti-TNF antibody approved for use in adults was infliximab (Remicade, Janssen Biotech). It is a chimeric monoclonal antibody consisting of 3/4 human and 1/4 murine sequences. It binds to both circulating and cell-bound forms of the proinflammatory cytokine TNF-α, thereby neutralizing TNF-α and causing apoptosis of activated lymphocytes (7, 8). Historically, indications for this medication have been extended from treatment of refractory Crohn’s disease in adults only to induction and maintenance therapy in luminal and fistulizing Crohn’s disease in adults and children, as well as treatment of adults and now (since 2011) children with moderate-to-severe ulcerative colitis unresponsive to conventional treatment (9-11). According to actual ECCO and ESPGHAN evidence-based consensus guidelines about management of pediatric ulcerative colitis infliximab should be considered for treatment of children with persistently active, or steroid-dependent UC, uncontrolled by 5-ASA and thiopurines and may be considered for steroid-refractory (oral or intravenous) disease (12). In Poland, the drug is approved for the treatment of severely active ulcerative colitis in children and adolescents aged 6 to 17 years with an inadequate response to conventional therapies, including corticosteroids and 6-MP or AZA, or who are intolerant, or have medical contraindications for such therapies. The medication is given as an intravenous infusion, the recommended dose is 5 mg/kg (3 induction infusions in scheme 0, 2, 6 weeks, then if patient responded to the treatment subsequent infusions every 8 weeks for maintenance). In some cases, especially when a patient has lost response it is recommended to increase the dosage to 10 mg/kg or to reduce the interval between doses (13). To optimize the treatment it is advisable to measure infliximab level and antibodies to infliximab (14). If there are low levels and negative antibodies, then dose escalation may be indicated. Undetectable infliximab levels in the presence of antibodies may indicate loss of response and the need for dose escalation or switching to a different drug. Normal infliximab level suggests primary nonresponse or an alternative diagnosis as a cause of symptoms.
The definitive evidence for the efficacy of infliximab in adult UC was provided by two randomized, double--blind, placebo-controlled studies the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2) in 2005 (15). In each study, 364 patients were randomized to receive either infliximab (5 or 10 mg/kg intravenously) or placebo at weeks 0, 2, and 6, then every 8 weeks for a total of 46 weeks in ACT 1 or 22 weeks in ACT 2. At week 8 in ACT 1, 69.4% of patients in the group receiving infliximab 5 mg/kg and 61.5% of patients in the group receiving 10 mg of infliximab had had a clinical response, as compared with 37.2 percent of patients in the placebo group and in ACT 2 64.5% of patients in the group receiving lower dose of infliximab and 69.2% of patients in the group receiving higher dose of medication had had a clinical response, as compared with 29.3% of patients in the placebo group. Furthermore, in the infliximab group more patients sustained this clinical response, demonstrated mucosal healing, and had greater decreases in their median daily corticosteroid dose. The pooled data analysis of two studies also showed improvement in the quality of life of patients treated with infliximab, reduction in the number of hospitalizations due to ulcerative colitis and the number of surgical procedures. Colectomy was performed in 11.6% of patients treated with infliximab at a lower dose, in 7.4% of patients who received the drug in higher doses and in patients receiving placebo in 14.8% of cases. A systematic review of seven randomized controlled trials (RCTs) published in 2006 also evaluating the efficacy of infliximab concluded that it was effective for inducing clinical remission, clinical response, promoting mucosal healing, and reducing the need for colectomy in the short term in patients with moderate to severe UC refractory to corticosteroids and/or immunomodulators (16). Gisbert et al. one year later in 2007 performed a systematic review and meta-analysis on the efficacy and tolerance of infliximab in ulcerative colitis. Only randomized clinical trials comparing the efficacy of infliximab vs. placebo or steroids in patients with UC were included. According to that analysis infliximab is more effective than placebo, with an NNT from 3 to 5, for the treatment of moderate-to--severe UC, achieving clinical remission in 40% of the patients at approximately 9 months of follow-up (17).

Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.

Płatny dostęp do wszystkich zasobów Czytelni Medycznej

Aby uzyskać płatny dostęp do pełnej treści powyższego artykułu oraz WSZYSTKICH około 7000 artykułów Czytelni, należy wprowadzić kod:

Kod (cena 30 zł za 30 dni dostępu) mogą Państwo uzyskać, przechodząc na tę stronę.
Wprowadzając kod, akceptują Państwo treść Regulaminu oraz potwierdzają zapoznanie się z nim.

Piśmiennictwo
1. Sawczenko A, Sandhu BK: Presenting feature of inflammatory bowel disease in Great Britan and Ireland. Arch Dis Child 2003; 88(11): 995-1000.
2. Hyams J, Davis P, Lerer T et al.: Clinical outcome of ulcerative proctitis in children. J Pediatr Gastroenterol Nutr 1997; 25(2): 149-152.
3. Van Limbergen J, Russel RK, Drummond E et al.: Definition of phenotypic characteristics of childhood – onset inflammatory bowel disease. Gastroenterology 2008; 135: 1114-1122.
4. Griffiths AM: Specificities of inflammatory bowel disease in childhood. Best Pract Res Clin Gastroenterol 2004; 18: 509-523.
5. Goodhand J, Dawson R, Hefferon M et al.: Inflammatory bowel disease in young people: the case for transitional clinics. Inflamm Bowel Dis 2010; 16: 947-952.
6. Uchida K, Araki T, Toiyama Y et al.: Preoperative steroid-related complications in Japanese pediatric patients with ulcerative colitis. Dis Colon Rectum 2006; 49(1): 74-79.
7. Caviglia R, Boskoski I, Cicala M: Maintenance treatment with infliximab for the management of Crohn’s disease in adults. Biologics 2009; 3: 39-49.
8. Papa A, Mocci G, Bonizzi M et al.: Use of infliximab in particular clinical settings: management based on current evidence. Am J Gastroenterol 2009; 104(6): 1575-1586.
9. Turner D, Mack D, Leleiko N et al.: Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology 2010; 138: 2282-2291.
10. Mahadevan U, Cucchiara S, Hyams JS et al.: The London Position Statement of the World Congress of Gastroenterology on biological therapy for IBD with the European Crohn’s and Colitis Organisation: pregnancy and pediatrics. Am J Gastroenterol 2011; 106: 214-223.
11. Lichtenstein GR, Abreu MT, Cohen R, Tremaine W: American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006; 130: 935-939.
12. Turner D, Levine A, Escher JC et al.: Management of Pediatric Ulcerative Colitis: Joint ECCO and ESPGHAN Evidence-based Consensus Guidelines JPGN 2012; 55: 340-361.
13. Chaparro M, Guerra I, Munoz-Linares P et al.: Systematic review: antibodies and anti-TNF-alpha levels in inflammatory bowel disease. Aliment Pharmacol Ther 2012; 35: 971-986.
14. AfifW, Loftus EV Jr, Faubion WA et al.: Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol 2010; 105: 1133-1139.
15. Rutgeerts P, Sandborn WJ, Feagan BG et al.: Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005; 353: 2462-2476.
16. Lawson MM, Thomas AG, Akobeng AK: Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2006; CD005112.
17. Gisbert JP, González-Lama Y, Matè J: Systematic review: Infliximab therapy in ulcerative colitis. Aliment Pharmacol Ther 2007 Jan 1; 25(1): 19-37.
18. Mamula P, Markowitz JE, Brown KA et al.: Infliximab as a novel therapy for pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr 2002; 34(3): 307-311.
19. Mamula P, Markowitz JE, Cohen LJ et al.: Infliximab in pediatric ulcerative colitis: two-year follow-up. J Pediatr Gastroenterol Nutr 2004; 38(3): 298-301.
20. Russell GH, Katz AJ: Infliximab is effective in acute but not chronic childhood ulcerative colitis. J Pediatr Gastroenterol Nutr 2004; 39(2): 166-170.
21. Eidelwein AP, Cuffari C, Abadom V, Oliva-Hemker M: Infliximab efficacy in pediatric ulcerative colitis. Inflamm Bowel Dis 2005; 11(3): 213-218.
22. Fanjiang G, Russell GH, Katz AJ: Short- and long-term response to and weaning from infliximab therapy in pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr 2007; 44(3): 312-317.
23. Cucchiara S, Romeo E, Viola F et al.: Infliximab for pediatric ulcerative colitis: a retrospective Italian multicenter study. Dig Liver Dis 2008; 40 (suppl. 2): S260-S264.
24. McGinnis JK, Murray KF: Infliximab for ulcerative colitis in children and adolescents. J Clin Gastroenterol 2008; 42(8): 875-879.
25. Tiemi J, Komati S, Sdepanian VL: Effectiveness of infliximab in Brazilian children and adolescents with Crohn disease and ulcerative colitis according to clinical manifestations, activity indices of inflammatory bowel disease, and corticosteroid use. J Pediatr Gastroenterol Nutr 2010; 50(6): 628-633.
26. Hyams J, Damaraju L, Blank M et al.: Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol 2012; 10: 391-399.
27. Turner D, Griffiths AM: Acute severe ulcerative colitis in children: a systematic review. Inflamm Bowel Dis 2011; 17: 440-449.
28. HUMIRA (adalimumab) subcutaneous injection (product monograph). IL: Abbott Laboratories, Ltd, North Chicago 2012.
29. Burness CB, Keating GM: Adalimumab: A Review of Its Use in the Treatment of Patients with Ulcerative Colitis. BioDrugs 2013 Apr 12.
30. Reinisch W, Sandborn WJ, Hommes DW et al.: Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut 2011; 60: 780-787.
31. Sandborn WJ, van Assche G, Reinisch W et al.: Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2012 Feb; 142(2): 257-265.e1-3. doi: 10.1053/j.gastro.2011.10.032. Epub 2011 Nov 4.
32. Afif W, Leighton JA, Hanauer SB et al.: Open-label study of adalimumab in patients with ulcerative colitis including those with prior loss of response or intolerance to infliximab. Inflamm Bowel Dis 2009; 15(9): 1302-1307.
33. Hudis N, Rajca B, Polyak S et al.: The outcome of active ulcerative colitis treated with adalimumab. Gastroenterology 2009; 136 (5 suppl. 1): A661.
34. Gies N, Kroeker KI, Wong K, Fedorak RN: Treatment of ulcerative colitis with adalimumab or infliximab: long-term follow-up of a single-centre cohort. Aliment Pharmacol Ther 2010; 32(4): 522-528.
35. Taxonera C, Estellès J, Fernández-Blanco I et al.: Adalimumab induction and maintenance therapy for patients with ulcerative colitis previously treated with infliximab. Aliment Pharmacol Ther 2011; 33(3): 340-348.
36. McDermott E, Murphy S, Keegan D et al.: Efficacy of Adalimumab as a long term maintenance therapy in ulcerative colitis. J Crohns Colitis 2013 Mar; 7(2): 150-153.
37. Feagan BG, Sandborn WJ, Lazar A et al.: Adalimumab Therapy is Associated with Reduced Risk of Hospitalization in Patients with Ulcerative Colitis. Gastroenterology 2013 Sep 22. pii: S0016-5085(13)01360-7.
38. Italian Group for the Study of Inflammatory Bowel Disease: Adalimumab in active ulcerative colitis: A “real-life” observational study. Dig Liver Dis 2013 Sep; 45(9): 738-743.
39. Armuzzi A, Pugliese D, Nardone OM et al.: Management of difficult-to-treat patients with ulcerative colitis: focus on adalimumab. Drug Des Devel Ther 2013 Apr 8; 7: 289-296.
40. Russell RK, Wilson ML, Loganathan S et al.: A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33: 946-953.
41. Noe JD, Pfefferkorn M: Short-term response to adalimumab in childhood inflammatory bowel disease. Inflamm Bowel Dis 2008; 14(12): 1683-1687.
42. Sandborn WJ, Feagan BG, Marano C et al.: Subcutaneous Golimumab Induces Clinical Response and Remission in Patients with Moderate-To-Severe Ulcerative Colitis. Gastroenterology 2013 Jun 1. pii: S0016-5085(13)00846-9.
43. Danese S: IBD: Golimumab in ulcerative colitis: a “mènage à trois” of drugs. Nat Rev Gastroenterol Hepatol 2013 Sep; 10(9): 511-512.
44. Bousvaros A: Use of immunomodulators and biologic therapies in children with inflammatory bowel disease. Expert Rev Clin Immunol 2010; 6(4): 659-666.
45. Bradley GM, Oliva-Hemker M: Pediatric ulcerative colitis: current Treatment approaches including role of infliximab. Biologics: Targets and Therapy 2012; 6: 125-134.
46. de Bie CI, Escher JC, de Ridder L: Antitumor necrosis factor treatment for pediatric inflammatory bowel disease. Inflamm Bowel Dis 2012 May; 18(5): 985-1002. doi: 10.1002/ibd.21871. Epub 2011 Sep 20.
47. Dignass A, Lindsay JO, Sturm A et al.: Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis 2012; 6(10): 991-1030.
48. Danese S: New therapies for inflammatory bowel disease: from the bench to the bedside. Gut 2012; 61(6): 918-932.
49. Parikh A, Leach T, Xu J, Feagan B: P235. Long-term clinical experience with vedolizumab (VDZ) in patients with mild to moderate ulcerative colitis (UC). J Crohns Colitis 2012; 6 (suppl. 1): S103.
50. Feagan B, Rutgeerts P, Sands J et al.: 943b Induction therapy for ulcerative colitis: results of GEMINI I, a randomised placebo-controlled, double-blind, multicentre phase 3 trial. Gastroenterology 2012; 142(5): S160-S161.
51. Rutgeerts PJ: Vedolizumab induction therapy for ulcerative colitis: results of GEMINI I, a randomized, placebo-controlled, double-blind, multicentre phase 3 trial. Gut 2012; 2012 (suppl. 3): A65.
52. Rutgeerts PJ, Fedorak RN, Hommes DW et al.: A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis. Gut 2012 Jun 20. (Epub ahead of print).
otrzymano: 2013-12-20
zaakceptowano do druku: 2014-02-06

Adres do korespondencji:
*Anna Wiernicka
Department of Gastroenterology,
Hepatology and Feeding Disorders
Children’s Memorial Health Institute
Al. Dzieci Polskich 20, 04-730 Warszawa
tel. +48 (22) 815-73-84
a.janowska@czd.pl

Postępy Nauk Medycznych 3/2014
Strona internetowa czasopisma Postępy Nauk Medycznych