Research

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16 pages, 1374 KiB

Open AccessArticle

Adalimumab Persistence and Its Biosimilar in Inflammatory Bowel Disease: A Real-World Study

by María Carmen Fernández-Cano, Antonio Jesús Fernández-Cano, María Mar Martín-Rodríguez, Antonio Damián Sánchez-Capilla, María José Cabello-Tapia and Eduardo Redondo-Cerezo

J. Clin. Med. 2024, 13(2), 556; https://doi.org/10.3390/jcm13020556 - 18 Jan 2024

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Abstract

Adalimumab biosimilar experience is still recent. Interchangeability differences could reduce persistence times. Our goal was to compare biosimilar persistence differences with a reference. A retrospective observational study was performed in three groups divided according to the adalimumab received. The primary outcome measure was [...] Read more.

Adalimumab biosimilar experience is still recent. Interchangeability differences could reduce persistence times. Our goal was to compare biosimilar persistence differences with a reference. A retrospective observational study was performed in three groups divided according to the adalimumab received. The primary outcome measure was persistence, represented with Kaplan–Meier analysis, and we secondarily evaluated security, efficacy, and biomarkers. We obtained approval from the regional ethical committee, and the study was conducted following the Helsinki Declaration as revised in 2013. Data from 104 patients were collected: 50 received the biosimilar, 29 received the reference, and 25 switched from the original to the biosimilar. After a follow-up of 12 months, the biosimilar’s persistence was higher, without differences in mild adverse events per group. In contrast, there were differences in severe events, with the switched group’s frequency being higher. Biomarkers were reduced at similar proportions in all groups, and 43% had a clinical response at week 20 without differences. Adalimumab biosimilars are a valuable option for IBD based on clinical equivalence that are less expensive than the original drug. Their use does not have a detrimental influence on disease, although there are a few nuances in terms of interchangeability. These results support increasing confidence in using biosimilars, thus promoting the better sustainability of health systems. Full article

(This article belongs to the Special Issue Optimizing Present and Future Therapeutic Choices for Treatment and Management of Chronic Inflammatory Bowel Diseases)

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12 pages, 1613 KiB

Open AccessArticle

Safety and Effectiveness of Vedolizumab and Ustekinumab in Elderly Patients with Inflammatory Bowel Disease: A Real-Life Multicentric Cohort Study

by Tom Holvoet, Marie Truyens, Cara De Galan, Harald Peeters, Francisco Mesonero Gismero, Ainara Elorza, Paola Torres, Liv Vandermeulen, Aranzazu Jauregui-Amezaga, Rocio Ferreiro-Iglesias, Yamile Zabana, Laia Peries Reverter, Jeroen Geldof and Triana Lobatón

J. Clin. Med. 2024, 13(2), 365; https://doi.org/10.3390/jcm13020365 - 09 Jan 2024

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Abstract

Background: Data on ustekinumab and vedolizumab in the elderly inflammatory bowel disease (IBD) population are limited. The aim of the current study was to assess the safety and effectiveness of both in an elderly real-life population. Methods: A multicentric retrospective study was performed [...] Read more.

Background: Data on ustekinumab and vedolizumab in the elderly inflammatory bowel disease (IBD) population are limited. The aim of the current study was to assess the safety and effectiveness of both in an elderly real-life population. Methods: A multicentric retrospective study was performed on IBD patients who started vedolizumab or ustekinumab between 2010 and 2020. Clinical and endoscopic remission rates and (serious) adverse events (AE) were assessed. Results: A total of 911 IBD patients were included, with 171 (19%) aged above 60 (111 VDZ, 60 UST). Elderly patients treated with vedolizumab or ustekinumab had an increased risk for non-IBD hospitalization (10.5% vs. 5.7%, p = 0.021) and malignancy (2.3% vs. 0.5%, p = 0.045) compared to the younger population. Corticosteroid-free clinical (50% vs. 44%; p = 0.201) and endoscopic remission rates (47.9% vs. 31%, p = 0.07) at 1 year were similar. Comparing vedolizumab to ustekinumab in the elderly population, corticosteroid-free (47.9% vs. 31%, p = 0.061) and endoscopic remission rates (66.7% vs. 64.4%, p = 0.981) were similar. Vedolizumab- and ustekinumab-treated patients had comparable infection rates (13.5% vs. 10.0%, p = 0.504), IBD flare-ups (4.5% vs. 5%, p = 1.000), the occurrence of new EIMs (13.5% vs. 10%, p = 0.504), a risk of intestinal surgery (5.4% vs. 6.7%, p = 0.742), malignancy (1.8% vs. 3.3%, p = 0.613), hospitalization (9.9% vs. 11.7%, p = 0.721), and mortality (0.9% vs. 1.7%, p = 1.000). AE risk was associated only with corticosteroid use. Conclusions: Ustekinumab and vedolizumab show comparable effectiveness and safety in the elderly IBD population. Elderly IBD patients have an increased risk for non-IBD hospitalizations and malignancy compared to the younger IBD population, with corticosteroid use as the main risk factor. Full article

(This article belongs to the Special Issue Optimizing Present and Future Therapeutic Choices for Treatment and Management of Chronic Inflammatory Bowel Diseases)

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9 pages, 741 KiB

Open AccessArticle

Incidence of Myelotoxicity and Other Adverse Effects Related to Thiopurine Starting in Patients with Inflammatory Bowel Disease: Retrospective Observational Study in a Third-Level Hospital

by Gerard Grau, Eduard Brunet-Mas, Laura Patricia Llovet, Patricia Pedregal, Albert Villoria, Luigi Melcarne, Anna Puy, Belen Garcia-Sague, Luis Enrique Frisancho, María José Ramírez-Lázaro, Sergio Lario and Xavier Calvet

J. Clin. Med. 2023, 12(20), 6571; https://doi.org/10.3390/jcm12206571 - 17 Oct 2023

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Abstract

Background and objectives: Thiopurines are an effective treatment for the maintenance of remission in inflammatory bowel disease (IBD). They can present adverse effects (AEs), with myelotoxicity being the most relevant. This study aims to determine the incidence of AEs related to the starting [...] Read more.

Background and objectives: Thiopurines are an effective treatment for the maintenance of remission in inflammatory bowel disease (IBD). They can present adverse effects (AEs), with myelotoxicity being the most relevant. This study aims to determine the incidence of AEs related to the starting of thiopurines in our centre. Methodology: Retrospective study. The AEs in patients that were started on thiopurines between January 2016 and June 2020 were registered, with a two-year follow-up. The mean and standard deviation were used to describe the quantitative variables, and percentages and confidence intervals were used for the qualitative variables. The statistical significance was set at a p-value < 0.05. Results: 98 patients were included, with 64 AEs detected in 48 patients (49%). Most of the AEs appeared in the first 6 months. The most relevant were: 21 neutropenia (21.4%), 19 hypertransaminasemia (19.4%), 13 digestive intolerances (13.2%), 6 acute pancreatitis (6.12%), 3 phototoxicity (3%), and 2 unknown origin fevers (2%). In 29 patients (29.4%) the treatment had to be suspended due to AEs. In 11 cases (11.2%), azathioprine (AZA) was switched to 6-mercaptopurine (6 MP) as 5 showed tolerance and 6 patients needed suspension due to AEs. Eight patients required hospital admission, but none of them needed intensive care unit admission. There were no fatal adverse effects. Conclusions: Thiopurines are a safe drug with few AEs, especially after the first months of treatment. These results suggest that periodic analytic follow-up may not be necessary after the initial period of treatment. Full article

(This article belongs to the Special Issue Optimizing Present and Future Therapeutic Choices for Treatment and Management of Chronic Inflammatory Bowel Diseases)

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10 pages, 841 KiB

Open AccessArticle

Response to Ustekinumab Therapy Is Associated with an Improvement of Nutritional Status in Patients with Crohn’s Disease

by Lorenzo Bertani, Claudia D’Alessandro, Marco Fornili, Francesca Coppini, Federico Zanzi, Luca Carmisciano, Francesca Geri, Giovanni Baiano Svizzero, Emma Maria Rosi, Alice De Bernardi, Linda Ceccarelli, Maria Gloria Mumolo, Laura Baglietto, Massimo Bellini, Nicola De Bortoli and Francesco Costa

J. Clin. Med. 2023, 12(19), 6118; https://doi.org/10.3390/jcm12196118 - 22 Sep 2023

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Abstract

The presence of sarcopenia has been associated with the worst outcome of Crohn’s disease (CD). At present, no studies have evaluated the impact of ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate [...] Read more.

The presence of sarcopenia has been associated with the worst outcome of Crohn’s disease (CD). At present, no studies have evaluated the impact of ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate whether UST treatment could modify the parameters of body composition as assessed by bioelectrical impedance assay (BIA) in patients with CD. We prospectively enrolled consecutive patients with CD treated with UST, evaluating the therapeutic outcome at week 48 in terms of clinical remission and mucosal healing. BIA was performed at baseline and at week 48, assessing body cellular mass, total body water, phase angle, and body mass index. Out of 44 patients enrolled, 26 (59%) were in clinical remission and 22 (50%) achieved mucosal healing at the end of follow up. No significant differences were observed at baseline in all the BIA parameters between responders and non-responders. Phase angle increased over time in responders, while this was not observed in non-responders (test for the interaction between time and outcome, p-value = 0.009 and 0.007 for clinical remission and mucosal healing, respectively). The same differential increase was observed for body cellular mass (test for the interaction between time and outcome, p-value = 0.03 and 0.05 for clinical remission and mucosal healing, respectively). Total body water and BMI increased homogenously over time regardless of the outcomes (tests for the association with time, p-values of 0.01). To conclude, responsiveness to UST therapy seems to be associated with body composition modifications in patients with CD. In particular, the increase in phase angle in responders suggests that a significant improvement of nutritional status occurred in these patients. Full article

(This article belongs to the Special Issue Optimizing Present and Future Therapeutic Choices for Treatment and Management of Chronic Inflammatory Bowel Diseases)

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Review

Jump to: Research

26 pages, 936 KiB

Open AccessReview

Management of Post-Operative Crohn’s Disease: Knowns and Unknowns

by Matteo Spertino, Roberto Gabbiadini, Arianna Dal Buono, Anita Busacca, Gianluca Franchellucci, Giulia Migliorisi, Alessandro Repici, Antonino Spinelli, Cristina Bezzio and Alessandro Armuzzi

J. Clin. Med. 2024, 13(8), 2300; https://doi.org/10.3390/jcm13082300 - 16 Apr 2024

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Abstract

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by relapsing–remission phases. CD often requires surgical intervention during its course, mainly ileo-cecal/ileo-colonic resection. However, surgery in CD is not curative and post-operative recurrence (POR) can happen. The management of [...] Read more.

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by relapsing–remission phases. CD often requires surgical intervention during its course, mainly ileo-cecal/ileo-colonic resection. However, surgery in CD is not curative and post-operative recurrence (POR) can happen. The management of CD after surgery presents challenges. Ensuring timely, effective, and safe therapy to prevent POR is essential but difficult, considering that approximately 20–30% of subjects may not experience endoscopic POR and that 40–50% will only exhibit intermediate lesions, which carry a low risk of mid- and long-term clinical and surgical POR. Currently, there are two accepted intervention strategies: early post-operative prophylactic therapy (systematically or based on the patient’s risk of recurrence) or starting therapy after confirming endoscopic POR 6–12 months after surgery (endoscopy-driven prophylactic therapy). The risk of overtreatment lies in exposing patients to undesired adverse events, along with the costs associated with medications. Conversely, undertreatment may lead to missed opportunities to prevent bowel damage and the necessity for additional surgery. This article aims to perform a comprehensive review regarding the optimal strategy to reduce the risk of POR in CD patients and the current therapeutic options. Full article

(This article belongs to the Special Issue Optimizing Present and Future Therapeutic Choices for Treatment and Management of Chronic Inflammatory Bowel Diseases)

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13 pages, 624 KiB

Open AccessReview

Current Approaches for Monitoring of Patients with Inflammatory Bowel Diseases: A Narrative Review

by Alessandro Vitello, Marcello Maida, Endrit Shahini, Fabio Salvatore Macaluso, Ambrogio Orlando, Mauro Grova, Daryl Ramai, Gaetano Serviddio and Antonio Facciorusso

J. Clin. Med. 2024, 13(4), 1008; https://doi.org/10.3390/jcm13041008 - 09 Feb 2024

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Abstract

Background: Patients with inflammatory bowel diseases (IBD) require proactive monitoring both during the active phase to evaluate therapeutic response and during the remission phase to evaluate relapse or colorectal cancer surveillance. However, monitoring may vary between patients with ulcerative colitis (UC) and Crohn’s [...] Read more.

Background: Patients with inflammatory bowel diseases (IBD) require proactive monitoring both during the active phase to evaluate therapeutic response and during the remission phase to evaluate relapse or colorectal cancer surveillance. However, monitoring may vary between patients with ulcerative colitis (UC) and Crohn’s disease (CD), with distinct tools and intervals. Methods: This narrative review aims to focus on modern approaches to IBD monitoring, considering international guidelines and expert consensus. Results: The most recent European diagnostic guidelines advocate a combination of clinical, laboratory, endoscopic, and radiological parameters to evaluate the disease course of patients with IBD. Unfortunately, the conventional symptom-based therapeutic approach does not improve long-term outcomes and there is no single ideal biomarker available. Endoscopy plays a key role in evaluating response to therapy as well as monitoring disease activity. Recently, bedside intestinal ultrasound (IUS) has gained increasing interest and diffusion as it appears to offer several advantages including the monitoring of therapeutic response. Conclusion: In light of growing clinical advances, we present a schematic evidence-based monitoring algorithm that can be easily applied in clinical practice which combines all major monitoring modalities, including noninvasive tools such as IUS and video-capsule endoscopy. Full article

(This article belongs to the Special Issue Optimizing Present and Future Therapeutic Choices for Treatment and Management of Chronic Inflammatory Bowel Diseases)

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18 pages, 609 KiB

Open AccessReview

Predictors of Efficacy of Janus Kinase Inhibitors in Patients Affected by Ulcerative Colitis

by Giuseppe Cuccia, Giuseppe Privitera, Federica Di Vincenzo, Lucia Monastero, Laura Parisio, Luigi Carbone, Franco Scaldaferri and Daniela Pugliese

J. Clin. Med. 2024, 13(3), 766; https://doi.org/10.3390/jcm13030766 - 29 Jan 2024

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Abstract

Personalised medicine and the identification of predictors of the efficacy of specific drugs represent the ultimate goal for the treatment of ulcerative colitis (UC) in order to break the current therapeutic ceiling. JAK inhibitors are a new class of advanced therapies, orally administered, [...] Read more.

Personalised medicine and the identification of predictors of the efficacy of specific drugs represent the ultimate goal for the treatment of ulcerative colitis (UC) in order to break the current therapeutic ceiling. JAK inhibitors are a new class of advanced therapies, orally administered, showing a good profile of efficacy and safety in both randomised controlled trials (RCTs) and real-world studies. Unfortunately, to date, it is not possible to draw the ideal profile of a patient maximally benefiting from this class of drugs to guide clinicians’ therapeutic choices. Baseline clinical activities and inflammatory biomarkers, as well as their early variation after treatment initiation, emerged as the main predictors of efficacy from post hoc analyses of RCTs with tofacitinib. Similar findings were also observed in the real-life studies including mainly patients with a history of pluri-refractoriness to biological therapies. At last, a few new biomarkers have been explored, even though they have not been validated in large cohorts. This paper provides a review of the current knowledge on clinical variables and biomarkers predicting response to JAK inhibitors in UC. Full article

(This article belongs to the Special Issue Optimizing Present and Future Therapeutic Choices for Treatment and Management of Chronic Inflammatory Bowel Diseases)

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12 pages, 3303 KiB

Open AccessReview

Racial Disparities in Infliximab Efficacy for Ulcerative Colitis: Evidence Synthesis and Effect Modification Assessment

by Stefanos Bonovas, Andreas G. Tsantes, Rozeta Sokou, Argirios E. Tsantes, Georgios K. Nikolopoulos and Daniele Piovani

J. Clin. Med. 2024, 13(2), 319; https://doi.org/10.3390/jcm13020319 - 05 Jan 2024

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Abstract

An increasing amount of research explores the role of race in clinical phenotypes and outcomes in ulcerative colitis (UC). We aimed to investigate racial differences in infliximab (IFX) treatment efficacy in UC. We used aggregate data from IFX trials and evidence synthesis methods [...] Read more.

An increasing amount of research explores the role of race in clinical phenotypes and outcomes in ulcerative colitis (UC). We aimed to investigate racial differences in infliximab (IFX) treatment efficacy in UC. We used aggregate data from IFX trials and evidence synthesis methods to generate race-specific efficacy estimates. Then, we tested the effect modification by race by comparing the race-specific estimates derived from independent evidence syntheses. We computed ratios of relative risks (RRRs) and performed tests of statistical interaction. We analyzed data from five randomized, placebo-controlled trials evaluating IFX as induction and maintenance therapy for adults with moderate-to-severe UC (875 participants; 45% Asians). We found no substantial evidence of racial differences concerning the efficacy of IFX in inducing clinical response (RRR = 0.89, 95% CI: 0.66–1.20; p = 0.44), clinical remission (RRR = 0.58, 95% CI: 0.24–1.44; p = 0.24), and mucosal healing (RRR = 0.99, 95% CI: 0.69–1.41; p = 0.95), or maintaining clinical remission (RRR = 0.81, 95% CI: 0.46–1.42; p = 0.45) and mucosal healing (RRR = 0.84, 95% CI: 0.48–1.46; p = 0.53), between Asian and Caucasian populations. Future clinical studies should expand the participation of racial minorities to comprehensively assess potential racial differences in the effectiveness of advanced therapies, including IFX, in the context of treating UC. Full article

(This article belongs to the Special Issue Optimizing Present and Future Therapeutic Choices for Treatment and Management of Chronic Inflammatory Bowel Diseases)

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