Biologics in Focus: A Comprehensive Review of the Current Biological Therapies for Ulcerative Colitis in the United Arab Emirates (UAE)
Abstract
:1. Introduction
2. Results
3. Methods
4. Discussion
4.1. Anti-Tumor Necrosis Factors
4.2. Infliximab (Remicade®)
4.2.1. Efficacy
4.2.2. Safety
4.3. Adalimumab (Humira®)
4.3.1. Efficacy
4.3.2. Safety
4.4. Golimumab (Simponi®)
4.4.1. Efficacy
4.4.2. Safety
4.5. Anti-Integrin
4.5.1. Vedolizumab (Entyvio®)
4.5.2. Efficacy
4.5.3. Safety
4.6. Anti-Interleukin
4.6.1. Ustekinumab (Stelara®)
4.6.2. Efficacy
4.6.3. Safety
4.7. Janus Kinase Inhibitors
4.7.1. Tofacitinib (Xeljanz®)
4.7.2. Efficacy
4.7.3. Safety
4.7.4. Upadacitinib (Rinvoq®)
4.7.5. Efficacy
4.7.6. Safety
4.8. Biosimilars
4.9. Considerations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Fakhoury, M.; Negrulj, R.; Mooranian, A.; Al-Salami, H. Inflammatory bowel disease: Clinical aspects and treatments. J. Inflamm. Res. 2014, 7, 113–120. [Google Scholar] [CrossRef] [PubMed]
- Sood, A.; Midha, V. Epidemiology of inflammatory bowel disease in Asia. Indian J. Gastroenterol. 2007, 26, 285–289. [Google Scholar] [PubMed]
- Wang, Y.F.; Zhang, H.; Ouyang, Q. Clinical manifestations of inflammatory bowel disease: East and West differences. J. Dig. Dis. 2007, 8, 121–127. [Google Scholar] [CrossRef] [PubMed]
- Imhann, F.; Vila, A.V.; Bonder, M.J.; Fu, J.; Gevers, D.; Visschedijk, M.C.; Spekhorst, L.M.; Alberts, R.; Franke, L.; van Dullemen, H.M.; et al. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut 2018, 67, 108–119. [Google Scholar] [CrossRef] [PubMed]
- Lamb, C.A.; Kennedy, N.A.; Raine, T.; Hendy, P.A.; Smith, P.J.; Limdi, J.K.; Hayee, B.; Lomer, M.C.E.; Parkes, G.C.; Selinger, C.; et al. British Society of Gastroenterology consensus guide-lines on the management of inflammatory bowel disease in adults. Gut 2019, 68, s1–s106. [Google Scholar] [CrossRef]
- European Crohn’s and Colitis Organisation. ECCO-EFCCA Patient Guidelines on Ulcerative Colitis (UC); European Federation of Crohn’s & Ulcerative Colitis Associations: Brussels, Belgium, 2017; Available online: http://www.efcca.org/sites/default/files/Ulcerative Colitis Patient Guidelines.pdf (accessed on 6 January 2020).
- Alkhatry, M.; Al-Rifai, A.; Annese, V.; Georgopoulos, F.; Jazzar, A.N.; Khassouan, A.M.; Koutoubi, Z.; Nathwani, R.; Taha, M.S.; Limdi, J.K. First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases: A 2020 Delphi consensus. World J. Gastroenterol. 2020, 26, 6710–6769. [Google Scholar] [CrossRef]
- Rutgeerts, P.; Sandborn, W.J.; Feagan, B.G.; Reinisch, W.; Olson, A.; Johanns, J.; Travers, S.; Rachmilewitz, D.; Hanauer, S.B.; Lichtenstein, G.R.; et al. Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis. N. Engl. J. Med. 2005, 353, 2462–2476. [Google Scholar] [CrossRef]
- Sands, B.E.; Tremaine, W.J.; Sandborn, W.J.; Rutgeerts, P.J.; Hanauer, S.B.; Mayer, L.; Targan, S.R.; Podolsky, D.K. Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: A pilot study. Inflamm. Bowel Dis. 2001, 7, 83–88. [Google Scholar] [CrossRef]
- Probert, C.S.J.; Hearing, S.D.; Schreiber, S.; Kühbacher, T.; Ghosh, S.; Arnott, I.D.R.; Forbes, A. Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: A randomised controlled trial. Gut 2003, 52, 998–1002. [Google Scholar] [CrossRef] [PubMed]
- Järnerot, G.; Hertervig, E.; Friis-Liby, I.; Blomquist, L.; Karlén, P.; Grännö, C.; Vilien, M.; Ström, M.; Danielsson, Å.; Verbaan, H.; et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: A randomized, placebo-controlled study. Gastroenterology 2005, 128, 1805–1811. [Google Scholar] [CrossRef] [PubMed]
- Reinisch, W.; Sandborn, W.J.; Hommes, D.W.; D’Haens, G.; Hanauer, S.; Schreiber, S.; Panaccione, R.; Fedorak, R.N.; Tighe, M.B.; Huang, B.; 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. [Google Scholar] [CrossRef]
- Sandborn, W.J.; van Assche, G.; Reinisch, W.; Colombel, J.; D’haens, G.; Wolf, D.C.; Kron, M.; Tighe, M.B.; Lazar, A.; Thakkar, R.B. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2012, 142, 257–265.e3. [Google Scholar] [CrossRef] [PubMed]
- Colombel, J.-F.; Sandborn, W.J.; Ghosh, S.; Wolf, D.C.; Panaccione, R.; Feagan, B.; Reinisch, W.; Robinson, A.M.; Lazar, A.; Kron, M.; et al. Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: Data from ULTRA 1, 2, and 3. Am. J. Gastroenterol. 2014, 109, 1771–1780. [Google Scholar] [CrossRef] [PubMed]
- Suzuki, Y.; Motoya, S.; Hanai, H.; Hibi, T.; Nakamura, S.; Lazar, A.; Robinson, A.M.; Skup, M.; Mostafa, N.M.; Huang, B.; et al. Four-year maintenance treatment with adalimumab in Jap-anese patients with moderately to severely active ulcerative colitis. J. Gastroenterol. 2017, 52, 1031–1040. [Google Scholar] [CrossRef] [PubMed]
- Travis, S.; Feagan, B.G.; Peyrin-Biroulet, L.; Panaccione, R.; Danese, S.; Lazar, A.; Robinson, A.M.; Petersson, J.; Pappalardo, B.L.; Bereswill, M.; et al. Effect of adalimumab on clinical outcomes and health-related quality of life among patients with ulcerative colitis in a clinical practice setting: Results from InspirADA. J. Crohn’s Colitis 2017, 11, 1317–1325. [Google Scholar] [CrossRef]
- Sandborn, W.J.; Feagan, B.G.; Marano, C.; Zhang, H.; Strauss, R.; Johanns, J.; Adedokun, O.J.; Guzzo, C.; Colombel, J.-F.; Reinisch, W.; et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2014, 146, 85–95. [Google Scholar] [CrossRef]
- Sandborn, W.J.; Feagan, B.G.; Marano, C.; Zhang, H.; Strauss, R.; Johanns, J.; Adedokun, O.J.; Guzzo, C.; Colombel, J.F.; Reinisch, W.; et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2014, 146, 96–109.e1. [Google Scholar] [CrossRef]
- Hibi, T.; Imai, Y.; Senoo, A.; Ohta, K.; Ukyo, Y. Efficacy and safety of golimumab 52-week maintenance therapy in Japanese patients with moderate to severely active ulcerative colitis: A phase 3, double-blind, randomized, placebo-controlled study-(PURSUIT-J study). J. Gastroenterol. 2017, 52, 1101–1111. [Google Scholar] [CrossRef]
- Telesco, S.E.; Brodmerkel, C.; Zhang, H.; Kim, L.L.-L.; Johanns, J.; Mazumder, A.; Li, K.; Baribaud, F.; Curran, M.; Strauss, R.; et al. Gene expression signature of prediction of golimumab response in a phase 2a open-label trial of patients with ulcerative colitis. Gastroenterology 2018, 155, 1008–1011.e8. [Google Scholar] [CrossRef]
- Feagan, B.G.; Rutgeerts, P.; Sands, B.E.; Hanauer, S.; Colombel, J.-F.; Sandborn, W.J.; Van Assche, G.; Axler, J.; Kim, H.-J.; Danese, S.; et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 2013, 369, 699–710. [Google Scholar] [CrossRef]
- Sands, B.E.; Peyrin-Biroulet, L.; Loftus, E.V.; Danese, S.; Colombel, J.-F.; Törüner, M.; Jonaitis, L.; Abhyankar, B.; Chen, J.; Rogers, R.; et al. Vedolizumab versus adalimumab for mod-erate-to-severe ulcerative colitis. N. Engl. J. Med. 2019, 381, 1215–1226. [Google Scholar] [CrossRef]
- Sandborn, W.J.; Su, C.; Sands, B.E.; D’haens, G.R.; Vermeire, S.; Schreiber, S.; Danese, S.; Feagan, B.G.; Reinisch, W.; Niezychowski, W.; et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 2017, 376, 1723–1736. [Google Scholar] [CrossRef] [PubMed]
- Sands, B.E.; Sandborn, W.J.; Panaccione, R.; O’brien, C.D.; Zhang, H.; Johanns, J.; Adedokun, O.J.; Li, K.; Peyrin-Biroulet, L.; Van Assche, G.; et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 2019, 381, 1201–1214. [Google Scholar] [CrossRef]
- Danese, S.; Vermeire, S.; Zhou, W.; Pangan, A.L.; Siffledeen, J.; Greenbloom, S.; Hébuterne, X.; D’Haens, G.; Nakase, H.; Panés, J.; et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: Results from three phase 3, multicentre, double-blind, randomised trials. Lancet 2022, 399, 2113–2128, Correction in Lancet 2022, 400, 996. [Google Scholar] [CrossRef] [PubMed]
- Jørgensen, K.K.; Olsen, I.C.; Goll, G.L.; Lorentzen, M.; Bolstad, N.; Haavardsholm, E.A.; Lundin, K.E.A.; Mørk, C.; Jahnsen, J.; Kvien, T.K.; et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): A 52-week, randomised, double-blind, non-inferiority trial. Lancet 2017, 389, 2304–2316. [Google Scholar] [CrossRef]
- Kaniewska, M.; Moniuszko, A.; Rydzewska, G. The efficacy and safety of the biosimilar product (Inflectra®) compared to the reference drug (Remicade®) in rescue therapy in adult patients with ulcerative colitis. Prz. Gastroenterol. 2017, 12, 169–174. [Google Scholar] [CrossRef]
- Shin, D.; Kim, Y.; Kim, Y.S.; Körnicke, T.; Fuhr, R. A randomized, phase I pharmacokinetic study comparing SB2 and infliximab ref-erence product (Remicade®) in healthy subjects. BioDrugs 2015, 29, 381–388. [Google Scholar] [CrossRef]
- Shin, D.; Kim, Y.; Kim, H.S.; Fuhr, R.; Körnicke, T. A phase I pharmacokinetic study comparing SB5, an adalimumab biosimilar, and adalimumab reference product (Humira®) in healthy subjects. Ann. Rheum. Dis. 2015, 74, 459–460. [Google Scholar] [CrossRef]
- Wang, Y.; Gao, Z.; Liu, Z.; Liu, G.; Qu, X.; Chen, J.; Ren, X.; Xu, Z.; Yang, H. A randomized, double-blind, single-dose, two-way, parallel phase I clinical study comparing the pharmacokinetics and safety of adalimumab injecta and Humira® in healthy Chinese male volunteers. Expert Opin. Biol. Ther. 2022, 22, 225–234. [Google Scholar] [CrossRef]
- Pugliese, D.; Felice, C.; Papa, A.; Gasbarrini, A.; Rapaccini, G.L.; Guidi, L.; Armuzzi, A. Anti TNF-α therapy for ulcerative colitis: Current status and prospects for the future. Expert Rev. Clin. Immunol. 2017, 13, 223–233. [Google Scholar] [CrossRef]
- Schroeder, K.W.; Tremaine, W.J.; Ilstrup, D.M. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. N. Engl. J. Med. 1987, 317, 1625–1629. [Google Scholar] [CrossRef]
- Wang, Q.; Wen, Z.; Cao, Q. Risk of tuberculosis during infliximab therapy for inflammatory bowel disease, rheumatoid arthritis, and spondyloarthropathy: A meta-analysis. Exp. Ther. Med. 2016, 12, 1693–1704. [Google Scholar] [CrossRef] [PubMed]
- Rutgeerts, P.; Feagan, B.G.; Marano, C.W.; Padgett, L.; Strauss, R.; Johanns, J.; Adedokun, O.J.; Guzzo, C.; Zhang, H.; Colombel, J.; et al. Randomised clinical trial: A placebo-controlled study of intravenous golimumab induction therapy for ulcerative colitis. Aliment. Pharmacol. Ther. 2015, 42, 504–514. [Google Scholar] [CrossRef] [PubMed]
- Lord, J.D.; Long, S.A.; Shows, D.M.; Thorpe, J.; Schwedhelm, K.; Chen, J.; Kita, M.; Buckner, J.H. Circulating integrin alpha4/beta7+ lymphocytes targeted by vedolizumab have a pro-inflammatory phenotype. Clin. Immunol. 2018, 193, 24–32. [Google Scholar] [CrossRef] [PubMed]
- Vermersch, P.; Kappos, L.; Gold, R.; Foley, J.; Olsson, T.; Cadavid, D.; Bozic, C.; Richman, S. Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy. Neurology 2011, 76, 1697–1704. [Google Scholar] [CrossRef]
- Benson, J.M.; Peritt, D.; Scallon, B.J.; Heavner, G.A.; Shealy, D.J.; Giles-Komar, J.M.; Mascelli, M.A. Discovery and mechanism of ustekinumab: A human monoclonal antibody targeting interleukin-12 and interleukin-23 for treatment of immune-mediated disorders. mAbs 2011, 3, 535–545. [Google Scholar] [CrossRef] [PubMed]
- Food and Drug Administration. STELARA® (Ustekinumab)—Highlights of Prescribing Information; Food and Drug Administration: Silver Spring, MD, USA, 2019. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761044s003lbl.pdf (accessed on 6 January 2020).
- European Medicines Agency. STELARA® (Ustekinumab)—Summary of Product Characteristics; European Medicines Agency: Amsterdam, The Netherlands, 2019; Available online: https://www.ema.europa.eu/en/documents/product-information/stelara-epar-product-information_en.pdf (accessed on 6 January 2020).
- Sabino, J.; Verstockt, B.; Vermeire, S.; Ferrante, M. New biologics and small molecules in inflammatory bowel disease: An update. Therap. Adv. Gastroenterol. 2019, 12, 1756284819853208. [Google Scholar] [CrossRef]
- Recommendations|Upadacitinib for Treating Moderately to Severely Active Ulcerative Colitis|Guidance|NICE. Available online: https://www.nice.org.uk/guidance/ta856/chapter/1-Recommendations (accessed on 6 January 2020).
- Danese, S.; Grisham, M.; Hodge, J.; Telliez, J.-B. JAK inhibition using tofacitinib for inflammatory bowel disease treatment: A hub for multiple inflammatory cytokines. Am. J. Physiol.-Gastrointest. Liver Physiol. 2016, 310, G155–G162. [Google Scholar] [CrossRef] [PubMed]
- Wollenhaupt, J.; Silverfield, J.; Lee, E.B.; Curtis, J.R.; Wood, S.P.; Soma, K.; Nduaka, C.I.; Benda, B.; Gruben, D.; Nakamura, H.; et al. Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies. J. Rheumatol. 2014, 41, 837–852. [Google Scholar] [CrossRef]
- Bachelez, H.; van de Kerkhof, P.C.M.; Strohal, R.; Kubanov, A.; Valenzuela, F.; Lee, J.-H.; Yakusevich, V.; Chimenti, S.; Papacharalambous, J.; Proulx, J.; et al. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: A phase 3 randomised non-inferiority trial. Lancet 2015, 386, 552–561. [Google Scholar] [CrossRef]
- Wasserbauer, M.; Hlava, S.; Drabek, J.; Stovicek, J.; Minarikova, P.; Nedbalova, L.; Drasar, T.; Zadorova, Z.; Dolina, J.; Konecny, S.; et al. Adalimumab biosimilars in the therapy of Crohn´s disease and ulcerative colitis: Prospective multicentric clinical monitoring. PLoS ONE 2022, 17, e0271299. [Google Scholar] [CrossRef] [PubMed]
Trial (Study Weeks) | Intervention | No. of Patients | % Remission * (p vs. Placebo) | % Adverse Events ** | % Infections ** | Most Common Adverse Event (%) |
---|---|---|---|---|---|---|
ACT1 2005 [8] (30) | Placebo | 121 | 14.9 | 85.1 | 38.8 | UC exacerbation (33.1) |
Infliximab 5 mg/kg | 121 | 38.8 (p < 0.001) | 87.6 | 43.8 | UC exacerbation (19.0) | |
Infliximab 10 mg/kg | 122 | 32.0 (p < 0.002) | 91.0 | 49.2 | UC exacerbation (21.3) | |
ACT2 2005 [8] (54) | Placebo | 123 | 5.7 | 73.2 | 23.6 | UC exacerbation (16.3) |
Infliximab 5 mg/kg | 121 | 33.9 (p < 0.001) | 81.8 | 27.3 | Headache (15.7) | |
Infliximab 10 mg/kg | 120 | 27.5 (p < 0.001) | 80.0 | 28.3 | Headache (21.7) | |
Sands et al., 2001 [9] (12) | Placebo | 3 | 0 | 100 | - | UC exacerbation (66.7) |
Infliximab 5 mg/kg | 3 | 66.7 # | 100 | - | Cellulitis (33.3) | |
Infliximab 10 mg/kg | 3 | 33.3 # | 100 | - | Headache (66.7) | |
Infliximab 20 mg/kg | 2 | 50 # | 100 | - | Pruritus (50.0) | |
Probert et al., 2003 [10] (6) | Placebo | 40 | 30 | 5 (SAE) | - | Sepsis/colectomy |
Infliximab 5 mg/kg | 41 | 39 (p = 0.76) | 0 (SAE) | - | - | |
Järnerot et al., 2005 [11] (12) | Placebo | 21 | 37.5 | 61.9 | 4.7 | Sepsis (8.3) |
Infliximab 5 mg/kg | 24 | 100 # | 54.1 | 8.3 | Arthralgia (14.3) | |
ULTRA1 2011 [12] (8) | Placebo | 130 | 9.2 | 48.4 | 15.7 | ISR (3.1) |
Adalimumab 160/80/40 mg | 130 | 18.5 (p = 0.031) | 50.2 | 14.3 | ISR (5.8) | |
ULTRA2 2012 [13] (52) | Placebo | 246 | 8.5 | 83.8 | 39.6 | ISR (3.8) |
Adalimumab 160/80/40 mg | 248 | 17.3 (p = 0.004) | 82.9 | 45.1 | ISR (12.1) | |
ULTRA3 2014 [14] (208) | Open-label, Adalimumab 40 mg weekly/fortnightly | 588 | 24.7 | 17.7 (E/100) | 344.6 (E/100) | UC exacerbation (25.2 E/100) |
Suzuki et al., 2017 [15] (196) | Open-label, Adalimumab 40 mg or 80 mg fortnightly | 126 | 19.2 | 431.5 (E/100) | 137.5 (E/100) | UC exacerbation (11.7 E/100) |
InspirADA 2017 [16] (26) | Open-label, adalimumab 160/80/40 mg | 463 | 48 | 74.3 | 29.6 | ISR (9.9) |
PURSUIT-SC 2014 [17] (6) | Placebo | 331 | 6.4 | 38.2 | 12.1 | Headache (5.2) |
Golimumab 200/100 mg | 331 | 17.8 (p = 0.0437) | 37.5 | 11.8 | Nasopharyngitis (3.3) | |
Golimumab 400/200 mg | 331 | 17.9 (p = 0.0008) | 38.9 | 12.3 | Headache (4.5) | |
PURSUIT-M 2014 [18] (54) | Placebo | 156 | 15.6 | 66 | 28.2 | UC exacerbation (18.6) |
Golimumab 50 mg | 151 | 23.2 (p = 0.122) | 72.7 | 39.0 | UC exacerbation (17.5) | |
Golimumab 100 mg | 151 | 27.8 (p = 0.004) | 73.4 | 39.0 | UC exacerbation (15.6) | |
PURSUIT-J 2017 [19] (52) | Placebo | 31 | 6.5 | 71 | 35.5 | Nasopharyngitis (22.6) |
Golimumab 100 mg | 32 | 50 # | 96.9 | 65.6 | Nasopharyngitis (53.1) | |
PROgECT 2018 [20] (50) | Open-label golimumab 200 mg/100 mg | 103 | 13.1 | 67 | 24.3 | UC exacerbation |
GEMINI-I Induction 2013 [21] (6) | Placebo | 149 | 5.4 | 46 | 15 | UC exacerbation (5) and headache (5) |
Double-blind vedolizumab 300 mg | 225 | 16.9 (p = 0.001) | 40 | 14 | Headache (7) | |
Open-label Vedolizumab 300 mg | 521 | - | 47 | 14 | Headache (8) | |
GEMINI-1 Maintenance 2013 [21] (52) | Placebo | 126 | 15.9 | 84 | 71 | Nasopharyngitis (12) |
Vedolizumab 300 mg every 4 weeks | 125 | 44.8 (p < 0.001) | 81 | 71 | Nasopharyngitis (14) | |
Vedolizumab 300 mg every 8 weeks | 122 | 41.8 (p < 0.001) | 82 | 71 | Nasopharyngitis (16) | |
VARSITY 2019 [22] (52) | Vedolizumab | 383 | 31.3 | 62.7 | 23.4 | UC exacerbation (11.5) |
Adalimumab | 386 | 22.5 (p = 0.006) ^ | 69.2 | 34.6 | UC exacerbation (16.3) | |
OCTAVE Induction 1 2017 [23] (8) | Placebo | 598 | 8.2 | 59.8 | 15.6 | Nasopharyngitis (7.4) |
Tofacitinib 10 mg | - | 18.5 (p = 0.007) | 56.5 | 23.3 | Headache (7.8) | |
OCTAVE Induction 2 2017 [23] (8) | Placebo | 541 | 3.6 | 52.7 | 15.2 | Headache (8.0) |
Tofacitinib 10 mg | - | 16.6 (p < 0.001) | 54.1 | 18.2 | Headache (7.7) | |
OCTAVE Sustain 2017 [23] (52) | Placebo | 593 | 11.1 | 75.3 | 24.2 | UC exacerbation (35.9) |
Tofacitinib 5 mg | - | 34.3 (p < 0.001) | 72.2 | 35.9 | UC exacerbation (18.2) | |
Tofacitinib 10 mg | - | 40.6 (p < 0.001) | 79.6 | 39.8 | UC exacerbation (14.8) | |
UNIFI Induction 2019 [24] (8) | Placebo | 319 | 5.3 | 48 | 15.4 | UC exacerbation (5.6) |
Ustekinumab 130 mg | 320 | 15.6 (p < 0.001) | 41.4 | 15.9 | Headache (6.9) | |
Ustekinumab 6 mg/kg | 322 | 15.5 (p < 0.001) | 50.6 | 15.9 | Headache (4.1) | |
UNIFI Maintenance 2019 [24] (52) | Placebo | 175 | 24 | 78.9 | 46.3 | UC exacerbation (28.6) |
Ustekinumab 90 mg every 12 weeks | 172 | 38.4 (p = 0.002) | 69.2 | 33.7 | Nasopharyngitis (18) | |
Ustekinumab 90 mg every 8 weeks | 176 | 43.8 (p < 0.001) | 77.3 | 48.9 | Nasopharyngitis (14.8) | |
U-ACCOMPLISH Induction [25] 2022 (8) | Placebo | 177 | 4.1 | 39.5 | 4 | Headache (5.1) |
Upadacitinib 45 mg | 345 | 33.5 (p < 0.0001) | 52.9 | 9 | Acne (7) | |
U-ACHIEVE Induction [25] 2022 (8) | Placebo | 155 | 5 | 62 | 5.2 | UC exacerbation (13.5) |
Upadacitinib 45 mg | 319 | 26.1 (p < 0.0001) | 56.4 | 6.9 | Neutropenia (5) Creatinine kinase elevation (5) | |
U-ACHIEVE Maintenance [25] 2022 (52) | Placebo | 149 | 12 | 76 | 18 | UC exacerbation (30) |
Upadacitinib 15 mg | 148 | 30.7 (p < 0.0001) | 78 | 25 | UC exacerbation (13) | |
Upadacitinib 30 mg | 154 | 39 (p < 0.0001) | 79 | 27 | Nasopharyngitis (14) |
Biologic | Biosimilar | Investigators | Design | Cohort | Outcome |
---|---|---|---|---|---|
Infliximab | Inflectra | Jørgensen et al., 2017 [26] | Phase IV, randomized, double-blind study | Adult patients on stable treatment with Infliximab >6 months | Rate of remission at 52 weeks higher for inflectra compared to infliximab (93% vs. 88%). Frequency of adverse events was similar |
Kaniewska et al., 2017 [27] | Phase III, open-label study | Acute severe UC | Similar rates of remission compared to infliximab (42% vs. 32%). No significant differences in safety | ||
Remicade | Shin et al., 2015 [28] | Phase I, randomized, single-blind study | Healthy subjects | Pharmacokinetic equivalence was demonstrated | |
Imraldi | Shin et al., 2015 [29] | Phase I study | Healthy subjects | Pharmacokinetic bioequivalence | |
Hyrimoz | Jaun-Lembach et al., 2017 [30] | Phase I study | N/A | Highly similar structure, purity, and biological activity |
Drug Name | Mechanism of Action | Trial identifier | Current Status |
---|---|---|---|
Adrilumab | α4β7 integrin antagonist | NCT01694485 | Phase II study |
Etrolizumab | α4β7 integrin antagonist | NCT02118584 | Phase III study |
Risankizumab | α4β7 integrin antagonist | NCT03398148 | Phase II/III study |
Mirikizumab | IL-23 inhibitor | NCT03518086 | Phase III study |
Spesolimab | IL-36 inhibitor | NCT03482635 | Phase II/III study |
Ontamalimab | MAdCAM-1 antagonist | NCT03290781 | Phase III study |
PF-00547659 | MAdCAM-1 antagonist | NCT01620255 | Phase II study |
Bertililumab | Chemokine CCL11 inhibitor | NCT01671956 | Phase II study |
Neihulizumab | PSGL-1/CD162 antagonist | NCT03298022 | Phase II study |
KHK4083 | OX40 receptor antagonist | NCT02647866 | Phase II study |
‘inflammatory bowel disease’, ‘IBD’, ‘ulcerative colitis’, ‘biologics’, ‘biosimilars’, ‘tumour necrosis factor’, ‘integrin’, ‘interleukin’, ‘Janus kinase’, ‘Adalimumab’, ‘Infliximab’, ‘Golimumab’, ‘Vedolizumab’, ‘Ustekinumab’, ‘Upadacitinib’, ‘Tofacitinib’ |
Parameter | Clinical Evaluation (One Option) | Score |
---|---|---|
| Normal number of stools | 0 |
1–2 stools more than normal | 1 | |
3–4 stools more than normal | 2 | |
≥5 stools more than normal | 3 | |
| No blood seen | 0 |
Streaks of blood with stool less than half the time | 1 | |
Obvious blood with stool most of the time | 2 | |
Blood alone passes | 3 | |
| Normal mucosa or inactive disease | 0 |
Mild disease (erythema, decreased vascular pattern, mild friability) | 1 | |
Moderate disease (marked erythema, absent vascular pattern, friability, erosions) | 2 | |
Severe disease (spontaneous bleeding, ulceration) | 3 | |
| Normal | 0 |
Mild disease | 1 | |
Moderate disease | 2 | |
Severe disease | 3 |
Score | Interpretation |
---|---|
0–2 | Remission (if one subscore = 2 and the other three = 0, this is classified as mild activity) |
3–5 | Mild activity |
6–10 | Moderate activity |
>10 | Severe activity |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
El-Sayed, A.; Oztumer, C.; Richards, C.; Salim, O.-A.; Sivakumar, M.; Alrubaiy, L. Biologics in Focus: A Comprehensive Review of the Current Biological Therapies for Ulcerative Colitis in the United Arab Emirates (UAE). Gastrointest. Disord. 2024, 6, 241-256. https://doi.org/10.3390/gidisord6010018
El-Sayed A, Oztumer C, Richards C, Salim O-A, Sivakumar M, Alrubaiy L. Biologics in Focus: A Comprehensive Review of the Current Biological Therapies for Ulcerative Colitis in the United Arab Emirates (UAE). Gastrointestinal Disorders. 2024; 6(1):241-256. https://doi.org/10.3390/gidisord6010018
Chicago/Turabian StyleEl-Sayed, Ahmed, Ceyhun Oztumer, Camellia Richards, Omar-Adam Salim, Mathuri Sivakumar, and Laith Alrubaiy. 2024. "Biologics in Focus: A Comprehensive Review of the Current Biological Therapies for Ulcerative Colitis in the United Arab Emirates (UAE)" Gastrointestinal Disorders 6, no. 1: 241-256. https://doi.org/10.3390/gidisord6010018