EUROPEAN REGISTRY ON HELICOBACTER PYLORI MANAGEMENT (HP-EUREG): ANALYSIS OF 2,254 EMPIRICAL RESCUE THERAPIES ON THIRD AND SUBSEQUENT LINES

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Introduction

Helicobacter pylori treatment´s effectiveness decreases as treatment eradication attempts fail.

Aims & Methods

To evaluate the use and effectiveness of empirical rescue therapies on third and subsequent lines, in Europe.
Sub-study of the the European Registry on H. pylori Management (Hp-EuReg), an international, multicenter, prospective, non-interventionist registry starting in 2013 aiming to evaluate the decisions and outcomes of H. pylori management by European gastroenterologists (38 countries, 400 researchers). All infected adult patients were systematically registered at AEG-REDCap e-CRF until December 2023, all cases with three or more eradication attempts were extracted. Only the empirically prescribed therapies were considered. Effectiveness was analysed by modified intention-to-treat (mITT) and per protocol (PP). Data were subject to quality review.

Results

In total, 3,351 rescue treatments were included: 2,349, 688, 228 and 86 in third-, fourth-, fifth- and sixth-line treatments, respectively. Mean age was 51 years, 68% of patients were women and 5.3% were allergic to penicillin. Sixty-eight different treatment schemes were used, being the three-in-one single-capsule bismuth quadruple therapy the most commonly prescribed (Table). Overall effectiveness was 73% by mITT, and 74% by PP analyses. Bismuth quadruple therapy as single-capsule provided the highest mITT overall cure rate (84%) and achieved 87% when optimised with high-dose PPIs (p>0.05). Quadruple PPI-bismuth-tetracycline-metronidazole achieved optimal eradication rate (91% by mITT), only when high-dose PPIs and 14-day prescriptions were used. The use of doxycycline instead of tetracycline was associated with lower eradication rates in classical bismuth quadruple therapies (p<0.05).

Table 1. Effectiveness of the most frequently prescribed empirical therapies on third and subsequent treatment lines.
mITT, modified intention-to-treat; PP, per-protocol; N, total number of patients analysed; 95% CI - confidence interval; PPI, Proton Pump Inhibitor; A, amoxicillin; B, bismuth; C, clarithromycin; D, doxycycline; L, levofloxacin; M, metronidazole; Tc, tetracycline; R, rifabutin; *, achieved over 90% effectiveness when optimised (high-dose PPIs and 14-days length).
		Modified intention-to-treat		Per-protocol
Rescue therapy	Use, N (%)	n	Effectiveness, % (95% CI)	n	Effectiveness, % (95% CI)
PPI-Single capsule B-Tc-M Triple PPI-A-L Triple PPI-A-R Quadruple PPI-A-L-B Quadruple PPI-B-Tc-M Quadruple PPI-C-A-M Quadruple PPI-B-D-M Triple PPI-C-A Triple PPI-A-M Overall	796 (25%) 486 (15%) 363 (11%) 275 (8.7%) 243 (7.7%) 147 (4.7%) 120 (3.8%) 75 (2.4%) 68 (2.2%) 3,161 (100%)	741 380 317 246 230 137 116 66 61 2,964	84 (81-87) 80 (76-84) 70 (65-75) 74 (69-80) 68 (62-74)* 65 (57-73) 63 (54-72) 59 (46-72) 59 (46-72) 73 (71-74)	718 374 309 239 222 134 112 64 59 2,875	85 (83-88) 81 (77-85) 71 (66-76) 75 (70-81) 69 (63-75) 66 (57-74) 63 (54-73) 59 (47-72) 59 (46-73) 74 (72-76)

Conclusion

Empirical rescue treatments in third and subsequent lines obtain, in general, suboptimal eradication rates in Europe; however, bismuth quadruple therapy as single-capsule obtained encouraging results. Only the optimised bismuth quadruple therapy achieved ≥90% effectiveness.

Disclosure

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from: Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé and Biocodex.
Olga P. Nyssen received research funding from: Mayoly, Allergan/Abbvie, Richen, Juvisé and Biocodex.

PRESCRIPTIONS AND EFFECTIVENESS OF 3,351 EMPIRICAL RESCUE THERAPIES ON THIRD AND SUBSEQUENT LINES: DATA FROM THE EUROPEAN REGISTRY ON HELICOBACTER PYLORI MANAGEMENT (HP-EUREG)

Olga P. Nyssen 1, Matteo Pavoni 2, Ana Garre 1, Doron Boltin 3, Ángeles Pérez-Aísa 4, Luis Ricardo Rodrigo Sáez 5, Laimas Jonaitis 6, Perminder S. Phull 7, Samuel J Martínez-Domínguez 8, Ian Beales 9, Jesús Barrio 10, Luis Bujanda Fernández de Piérola 11, Vladimir Milivojevic 12, Alfredo J. Lucendo 13, Jose Maria Huguet 14, Bojan Tepes 15, Frode Lerang 16, Manuel Pabon-Carrasco 17, Giuseppe Losurdo 18, Miguel Areia 19, Manuel Castro-Fernández 17, Pavel Bogomolov 20, Judith Gomez-Camarero 21, Javier Tejedor-Tejada 22, Maja Denkovski 23, Antonio Gasbarrini 24, Blas José Gómez Rodríguez 25, Pilar Mata-Romero 26, Fernando Bermejo 27, D. Martin-Holgado 26, György Miklós Buzás 28, Alma Keco-Huerga 17, Manuel Domínguez Cajal 29, Monica Perona 30, Oscar Núñez Martínez 31, Irina Voynovan 32, Sotirios Georgopoulos 33, Luis Hernández Villalba 34, Juozas Kupcinskas 6, Ricardo Pinto 35, Dmitry S. Bordin 36, Veronika Papp 37, Marcis Leja 38, Theodore Rokkas 39, Anna Cano Català 40, Pablo Parra 1, Leticia Moreira Ruiz 41, Francis Mégraud 42, Colm O'Morain 43, Javier Gisbert 1

1 Department of Gastroenterology, Hospital Universitario de La Princesa, IIS-Princesa, Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

2 Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi University Hospital, Bologna, Italy

3 Department of Gastroenterology, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel

4 Department of Gastroenterology, Hospital Universitario Costa del Sol, Redes de Investigación Cooperativa Orientada a Resultados en Salud (RICORS), Marbella, Spain

5 Department of Gastroenterology, Universidad de Oviedo, Oviedo, Spain

6 Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania

7 Department of Digestive Disorders, Aberdeen Royal Infirmary, Aberdeen, United Kingdom

8 Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, IIS Aragón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain

9 Norwich Medical School, University of East Anglia, Norwich, United Kingdom

10 Department of Gastroenterology, Hospital Universitario Río Hortega, Gerencia Regional de Salud de Castilla y León (SACYL), Valladolid, Spain

11 Department of Gastroenterology, Biodonostia Health Research Institute, Department of Medicine, Universidad del País Vasco (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), San Sebastián, Spain

12 Clinical Center of Serbia and School of Medicine, University of Belgrade, Belgrade, Serbia

13 Department of Gastroenterology, Hospital General de Tomelloso, IIS-Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Tomelloso, Spain

14 Department of Gastroenterology, Hospital General Universitario de Valencia, Valencia, Spain

15 Department of Gastroenterology, DC Rogaska, Rogaska Slatina, Slovenia

16 Østfold Hospital Trust, Grålum, Norway

17 Department of Gastroenterology, Hospital Universitario Virgen de Valme, Sevilla, Spain

18 Department of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, Bari, Italy

19 Department of Gastroenterology, Portuguese Oncology Institute of Coimbra, Faculty of Medicine of the University of Porto (FMUP), Center for Health Technology and Services Research (CINTESIS), Coimbra, Portugal

20 Universal Clinic Private Medical Center, Moscow, Russian Federation

21 Department of Gastroenterology, Hospital Universitario de Burgos, Burgos, Spain

22 Department of Gastroenterology, Hospital Universitario de Cabueñes, Gijón, Spain

23 Interni oddelek, Diagnostic Centre, Bled, Slovenia

24 Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

25 Department of Gastroenterology, Hospital Universitario Virgen Macarena, Sevilla, Spain

26 Department of Gastroenterology, Hospital Universitario de Cáceres, Cáceres, Spain

27 Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain

28 Department of Gastroenterology, Ferencváros Health Center, Budapest, Hungary

29 Department of Gastroenterology and Hepatology, Hospital Universitario San Jorge, Huesca, Spain

30 Department of Gastroenterology, Hospital Quirón Marbella, Marbella, Spain

31 Department of Gastroenterology, Hospital Universitario Sanitas La Moraleja, Madrid, Spain

32 A.S. Loginov Moscow Clinical Scientific Center, Moscow, Russian Federation

33 Athens Medical, P. Faliron General Hospital, Athens, Greece

34 Department of Gastroenterology, Hospital Santos Reyes, Aranda de Duero, Spain

35 Gastroenterology Department, Centro Hospitalar do Porto, Universidade do Porto, Instituto De Ciências Biomédicas de Abel Salazar, Center for Research in Health Technologies and Information Systems (CINTESIS), Porto, Portugal

36 Department of Pancreatic, Biliary and upper digestive tract disorders, A. S. Loginov Moscow clinical scientific center, Department of outpatient therapy and family medicine, Tver State Medical University, Moscow, Russian Federation

37 Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary

38 Department of Gastroenterology, Digestive Diseases Centre, Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia

39 Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece

40 Gastrointestinal Oncology, Endoscopy and Surgery (GOES) research group, Althaia Xarxa Assistencial Universitària de Manresa, Institut de Recerca i Innovació en Ciències de la Vida i de la Salut de la Catalunya Central (IRIS-CC), Manresa, Spain

41 Department of Gastroenterology, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelon

42 INSERM U1312, Université de Bordeaux, Bordeaux, France

43 School of Medicine, Trinity College Dublin, Dublin, Ireland

Conference

UEG Week Vienna 2024

Topics

Stomach & H. Pylori

Submission format

Abstract

Session

H.pylori treatment: Part 1 (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Introduction

After a first eradication attempt, approximately 10-20% of patients will fail to achieve H. pylori eradication.

Aims & Methods

To evaluate the effectiveness of second-line empirical treatment.
A systematic, prospective, registry of the clinical practice of European gastroenterologists (38 countries) on H. pylori management was established. All infected adult patients were systematically registered at AEG-REDCap e-CRF until December 2023. Modified intention-to-treat (mITT) and per-protocol (PP) analyses were performed.

Results

Overall, 8,984 patients received a second-line empirical therapy. Mean age was of 50 years, 66% were women, and 5% had penicillin allergy. Most frequent treatment indications were dyspepsia (70%) and gastroduodenal ulcer (15%). Overall effectiveness was 83% (both by mITT and PP). Over 96.5% of patients were compliant. Adverse events were reported in 23% of the cases, most of them mild. Most frequent second-line prescriptions and their effectiveness by region is shown in table 1. None of the European regions achieved an optimal effectiveness. However, in those patients receiving optimised therapy (i.e., 14-days and high dose PPIs), triple regimens containing levofloxacin and bismuth quadruple therapies either with metronidazole-tetracycline or clarithromycin-amoxicillin, as well as quadruple therapy with clarithromycin-amoxicillin-metronidazole, showed optimal effectiveness. Also, 10-day bismuth quadruple therapy as single-capsule achieved over 90% cure rates when prescribed with standard PPI doses. After failure of first-line clarithromycin-containing therapy, optimal eradication was only obtained with moxifloxacin-containing triple therapy (92%). Quadruple therapy with clarithromycin-amoxicillin-metronidazole and bismuth quadruple therapies either with clarithromycin-amoxicillin, amoxicillin-levofloxacin or the single-capsule provided encouraging results (>85%).

Table 1. Second-line empirical treatment prescriptions and effectiveness by treatment scheme and geographical region.
95% CI –confidence interval; mITT: modified intention-to-treat; PP: per-protocol, N: total number of patients analysed; C – clarithromycin; M – metronidazole; A – amoxicillin; L – levofloxacin; B – bismuth salts; Tc – tetracycline; R – rifabutin; Mx – moxifloxacin; Other – Other second-line empirical treatments with less than 150 patients treated in each category; East – Ukraine, Serbia, Bulgaria, Turkey, Russia , Romania, Albania, North Macedonia; East-Centre – Croatia, Poland, Hungary, Latvia, Lithuania, Greece, Slovenia, Czech Rep, Azerbaijan, Slovakia, Malta; South-West – Portugal, Spain; West-Centre – France, Austria, Belgium, Germany, Italy; North – United Kingdom, Finland, The Netherlands, Ireland, Israel, Norway, Switzerland, Sweden, Denmark; three-in-one single-capsule containing metronidazole tetracycline and bismuth; *achieved over 90% effectiveness when optimised (high-dose PPIs and 14-days length in all schemes but the single-capsule optimised with standard-dose PPIs).
Treatment	N	Use (%)	mITT, N (%)	(95% CI)	PP, N (%)	(95% CI)
Triple-A+L Single-capsule* Quadruple-A+L+B Quadruple-C+A+M Triple-C+A Quadruple-M+Tc+B Quadruple-C+A+B Triple-A+M Triple-A+R Triple-A+Mx Other Overall Overall (optimised conditions)	2,212 1,783 1,170 560 525 451 370 225 212 153 1,013 8,674 2,005	25.5 20.6 13.5 6.5 6.1 5.2 4.3 2.6 2.4 1.8 11.5 100 23.1	1,959 (81) 1,659 (88) 929 (85) 534 (85) 424 (79) 405 (83) 251 (89) 198 (62) 189 (83) 147 (92) NA 7,563 (83) 1,747 (89)	(79-83) (86-89) (83-87) (82-88) (75-83) (79-87) (85-93) (55-69) (77-88) (87-97) NA (82-84) (87-90)	1,936 (81) 1,621 (89) 910 (85) 523 (85) 416 (79) 386 (85) 240 (90) 195 (63) 187 (83) 147 (92) NA 7,410 (83) 1,709 (89)	(79-83) (87-90) (83-88) (82-89) (75-83) (81-88) (86-94) (56-70) (77-89) (87-97) NA (83-84) (88-91)
East East-Centre South-West West-Centre North Total	1,425 1,625 4,190 1,103 631 8,974	15.9 18.1 46.7 12.3 7.0 100	1,159 (84) 1,160 (84) 3,973 (83) 979 (84) 547 (72) 7,803 (83)	(82-86) (82-86) (82-85) (82-87) (68-76) (82-84)	1,121 (84) 1,147 (84) 3,895 (84) 962 (85) 530 (73) 7,641 (83)	(82-87) (82-87) (83-85) (82-87) (69-77) (83-84)

Conclusion

In Europe, empirical second-line treatment achieves optimal effectiveness with bismuth quadruple therapy as single-capsule when prescribed standard doses of PPIs, and when regimens including triple therapy with levofloxacin, quadruple therapy with clarithromycin-amoxicillin-metronidazole and bismuth quadruple therapies with metronidazole-tetracycline or clarithromycin-amoxicillin are prescribed for 14 days and with high-dose PPIs. Many other second-line treatments evaluated achieved low eradication rates.

Disclosure

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from: Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé and Biocodex.
Olga P. Nyssen received research funding from: Mayoly, Allergan/Abbvie, Richen, Juvisé and Biocodex.

EMPIRICAL SECOND-LINE TREATMENTS IN EUROPE: DATA FROM 9,000 CASES FROM THE EUROPEAN REGISTRY ON HELICOBACTER PYLORI MANAGEMENT (HP-EUREG)

Olga P. Nyssen 1, Laimas Jonaitis 2, Ángeles Pérez-Aísa 3, Luis Ricardo Rodrigo Sáez 4, Samuel J Martínez-Domínguez 5, Bojan Tepes 6, Liudmila Vologzhanina 7, Ana Garre 1, Luis Bujanda Fernández de Piérola 8, Manuel Pabon-Carrasco 9, Manuel Castro-Fernández 9, Frode Lerang 10, Irina Voynovan 11, Alfredo J. Lucendo 12, Jose Maria Huguet 13, Javier Tejedor-Tejada 14, Renate Bumane 15, Jesús Barrio 16, Pavel Bogomolov 17, Matteo Pavoni 18, Vladimir Milivojevic 19, B. Velayos 20, Maja Denkovski 21, Blas José Gómez Rodríguez 22, Thomas Butler 23, Fernando Bermejo 24, Giuseppe Losurdo 25, Miguel Areia 26, Aiman Sarsenbaeva 27, Alma Keco-Huerga 9, Oscar Núñez Martínez 28, Antonio Gasbarrini 29, Rustam A Abdulkhakov 30, Doron Boltin 31, Georges Kamtoh 32, Ian Beales 33, Juozas Kupcinskas 2, Luis Hernández Villalba 34, Dmitry S. Bordin 35, Marcis Leja 15, Sinead Smith 36, Ricardo Pinto 37, Wojciech Marlicz 38, Perminder S. Phull 39, Anna Cano Català 40, Pablo Parra 1, Leticia Moreira Ruiz 41, Francis Mégraud 42, Colm O'Morain 36, Javier Gisbert 1

1 Department of Gastroenterology, Hospital Universitario de La Princesa, IIS-Princesa, Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

2 Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania

3 Department of Gastroenterology, Hospital Universitario Costa del Sol, Redes de Investigación Cooperativa Orientada a Resultados en Salud (RICORS), Marbella, Spain

4 Department of Gastroenterology, Universidad de Oviedo, Oviedo, Spain

5 Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, IIS Aragón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain

6 Department of Gastroenterology, DC Rogaska, Rogaska Slatina, Slovenia

7 Gastrocentr, Perm, Russian Federation

8 Department of Gastroenterology, Biodonostia Health Research Institute, Department of Medicine, Universidad del País Vasco (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), San Sebastián, Spain

9 Department of Gastroenterology, Hospital Universitario Virgen de Valme, Sevilla, Spain

10 Østfold Hospital Trust, Grålum, Norway

11 A.S. Loginov Moscow Clinical Scientific Center, Moscow, Russian Federation

12 Department of Gastroenterology, Hospital General de Tomelloso, IIS-Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Tomelloso, Spain

13 Department of Gastroenterology, Hospital General Universitario de Valencia, Valencia, Spain

14 Department of Gastroenterology, Hospital Universitario de Cabueñes, Gijón, Spain

15 Department of Gastroenterology, Digestive Diseases Centre, Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia

16 Department of Gastroenterology, Hospital Universitario Río Hortega, Gerencia Regional de Salud de Castilla y León (SACYL), Valladolid, Spain

17 Universal Clinic Private Medical Center, Moscow, Russian Federation

18 Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi University Hospital, Bologna, Italy

19 Clinical Center of Serbia and School of Medicine, University of Belgrade, Belgrade, Serbia

20 Department of Gastroenterology, Hospital Clínico de Valladolid, Valladolid, Spain

21 Interni oddelek, Diagnostic Centre, Bled, Slovenia

22 Department of Gastroenterology, Hospital Universitario Virgen Macarena, Sevilla, Spain

23 Clinical Medicine, Trinity College Dublin, Department of Gastroenterology, Tallaght University Hospital, Dublin, Ireland

24 Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain

25 Department of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, Bari, Italy

26 Department of Gastroenterology, Portuguese Oncology Institute of Coimbra, Faculty of Medicine of the University of Porto (FMUP), Center for Health Technology and Services Research (CINTESIS), Coimbra, Portugal

27 Department of Gastroenterology, Chelyabinsk Regional Clinical Hospital, Chelyabinsk, Russian Federation

28 Department of Gastroenterology, Hospital Universitario Sanitas La Moraleja, Madrid, Spain

29 Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

30 Department of Hospital Medicine, Kazan State Medical University, Kazan, Russian Federation

31 Department of Gastroenterology, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel

32 Hepatic Medical, Private Medical Center, Krakow, Poland

33 Norwich Medical School, University of East Anglia, Norwich, United Kingdom

34 Department of Gastroenterology, Hospital Santos Reyes, Aranda de Duero, Spain

35 Department of Pancreatic, Biliary and upper digestive tract disorders, A. S. Loginov Moscow clinical scientific center, Department of outpatient therapy and family medicine, Tver State Medical University, Moscow, Russian Federation

36 School of Medicine, Trinity College Dublin, Dublin, Ireland

37 Gastroenterology Department, Centro Hospitalar do Porto, Universidade do Porto, Instituto De Ciências Biomédicas de Abel Salazar, Center for Research in Health Technologies and Information Systems (CINTESIS), Porto, Portugal

38 Department of Gastroenterology, Pomeranian Medical University in Szczecin, The Centre for Digestive Diseases, Endoklinika, Szczecin, Poland

39 Department of Digestive Disorders, Aberdeen Royal Infirmary, Aberdeen, United Kingdom