Adalimumab for induction of remission in Crohn's disease

Abbass, Mohamad; Cepek, Jeremy; Parker, Claire E; Nguyen, Tran M; MacDonald, John K; Feagan, Brian G.; Khanna, Reena; Jairath, Vipul

doi:10.1002/14651858.cd012878.pub2

Cited by 12 publications

(8 citation statements)

References 47 publications

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“…In particular, the class of anti-TNFα antibodies, mostly used for the treatment of inflammatory rheumatic diseases, could be able to challenge COVID-19 by two main actions: the classical TNFα inhibition and a down-regulation of ACE2 expression resulting in decreased binding sites for SARS-CoV-2 [ 72 , 73 ]. Thus, anti-TNFα antibodies, and adalimumab in particular thanks to its excellent safety profile [ 74 ], could inhibit the basic mechanisms of COVID-19, and could be potentially useful in managing/preventing COVID-19-driven pneumonia[ 75 ]. As proof of this, a study evaluating adalimumab injection in COVID-19 patients has recently been registered in order to assess the role of this antibody in treating COVID-19 patients with severe pneumonia [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

SAveRUNNER: A network-based algorithm for drug repurposing and its application to COVID-19

et al. 2021

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The novelty of new human coronavirus COVID-19/SARS-CoV-2 and the lack of effective drugs and vaccines gave rise to a wide variety of strategies employed to fight this worldwide pandemic. Many of these strategies rely on the repositioning of existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we presented a new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug–disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Specifically, we applied SAveRUNNER on a panel of 14 selected diseases with a consolidated knowledge about their disease-causing genes and that have been found to be related to COVID-19 for genetic similarity (i.e., SARS), comorbidity (e.g., cardiovascular diseases), or for their association to drugs tentatively repurposed to treat COVID-19 (e.g., malaria, HIV, rheumatoid arthritis). Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments (e.g., chloroquine, hydroxychloroquine, tocilizumab, heparin), as well as a new combination therapy of 5 drugs (hydroxychloroquine, chloroquine, lopinavir, ritonavir, remdesivir), actually used in clinical practice. Furthermore, to maximize the efficiency of putative downstream validation experiments, we prioritized 24 potential anti-SARS-CoV repurposable drugs based on their network-based similarity values. These top-ranked drugs include ACE-inhibitors, monoclonal antibodies (e.g., anti-IFNγ, anti-TNFα, anti-IL12, anti-IL1β, anti-IL6), and thrombin inhibitors. Finally, our findings were in-silico validated by performing a gene set enrichment analysis, which confirmed that most of the network-predicted repurposable drugs may have a potential treatment effect against human coronavirus infections.

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Section: Discussionmentioning

confidence: 99%

SAveRUNNER: A network-based algorithm for drug repurposing and its application to COVID-19

et al. 2021

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Section: Discussionmentioning

confidence: 99%

“…Four other systematic reviews that assessed the efficacy and safety of ADA in CD patients were identified [45][46][47][48]. Abbass et al [45] assessed the efficacy and safety of ADA in patients with moderately to severely active CD, which included three RCTs and concluded that ADA was effective for achieving short-term clinical response or remission in CD participants [18,33,34]. Huang et al [46,47] also assessed the efficacy and safety of ADA in inducing and maintaining remission of participants with moderate-to-severe CD, which included four RCTs and concluded that ADA was effective and significantly improved the life quality of CD participants [18,33,49,50].…”

Section: Discussionmentioning

confidence: 99%

Adalimumab for induction of remission in patients with Crohn's disease: a systematic review and meta-analysis

Yin

Chen

et al. 2022

Eur J Med Res

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Purpose A large number of people with Crohn's disease (CD) fail to recover from conventional therapy or biological therapy. Some studies showed that adalimumab (ADA) may be an effective alternative therapy for these patients. The aim of this study was to evaluate the efficacy and safety of ADA in inducing CD remission. Methods We performed search of Pubmed/MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register, and several other databases. Randomized controlled trials (RCTs) comparing any dose of ADA with controls (placebo or active) in participants with active CD were included. The primary outcome was the failure to achieve clinical response/remission at 4 weeks. Several subgroup and sensitivity analyses were performed. Review Manager Software v5.3 was used. Results Four RCTs were included (n = 919), in which 553 participants received ADA and 366 participants received placebo. A meta-analysis of four studies showed that at 4 weeks, there were more people in the ADA group with clinical response/remission or symptom improvement compared with the placebo group. The rates of side effects, serious side effects, and study withdrawals due to side effects were lower in ADA participants than placebo ones. Conclusion This meta-analysis shows that ADA is superior to placebo in induction of clinical response/remission of CD patients, but no firm conclusions can be drawn on the safety of ADA in CD due to the low number of events. Graphical Abstract

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“…The study endpoints were to evaluate the improvements in HRQOL and work productivity with upadacitinib after Weeks IBDQ is a disease-specific instrument that has been validated and commonly used for CD [17][18][19][20][21]. IBDQ is composed of 32 items graded on a 7-point Likert scale, which contains four dimensional score domains: bowel, emotional, social, and systemic [17][18][19].…”

Section: Discussionmentioning

confidence: 99%

“…IBDQ is a disease-specific instrument that has been validated and commonly used for CD [ 17 – 21 ]. IBDQ is composed of 32 items graded on a 7-point Likert scale, which contains four dimensional score domains: bowel, emotional, social, and systemic [ 17 – 19 ].…”

Section: Methodsmentioning

confidence: 99%

Quality of Life and Work Productivity Improvements with Upadacitinib: Phase 2b Evidence from Patients with Moderate to Severe Crohn’s Disease

et al. 2021

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Introduction: In the phase 2 CELEST study, positive efficacy results were obtained with the Janus kinase 1 inhibitor upadacitinib for adult patients with moderate to severe Crohn's disease. We present the health-related quality of life and work productivity improvement results with upadacitinib from CELEST. Methods: CELEST (NCT02365649) was a double-blind study where patients were randomized 1:1:1:1:1:1 in the 16-week induction period to placebo or upadacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg BID, 24 mg BID, or 24 mg once daily (QD). Patients completing the induction period were re-randomized 1:1:1 to receive upadacitinib 3 mg BID, 12 mg BID, or 24 mg QD for 36 weeks or 3 mg BID, 6 mg BID, or 12 mg BID (after amendment). Inflammatory Bowel Disease Questionnaire (IBDQ), European Quality of Life-5 Dimensions visual analog scale (EQ-5D VAS), and Work Productivity and Activity Impairment (WPAI) questionnaire outcomes were assessed at baseline and Weeks 8, 16, and 52. Results: At Week 16, a significant percentage (P B 0.05) of patients receiving upadacitinib 6-mg BID dose or higher achieved IBDQ response (IBDQ score change C 16 points; 49%-57% for upadacitinib vs. 24% for placebo) and IBDQ remission, except 24 mg QD (IBDQ score C 170; 26%-39% for upadacitinib vs. 11% for placebo). Greater improvements in IBDQ total score, EQ-5D VAS, and activity impairment from baseline (P B 0.1) versus placebo were also observed. Larger improvements (P B 0.1) in IBDQ response and total score and EQ-5D VAS were observed at Week 8 with 6 and 24 mg BID versus placebo, with improvements for all dosages maintained or greater at Week 52 for IBDQ, EQ-5D VAS, and WPAI endpoints, in particular for the 12-mg BID group. Conclusion: Improvements in health-related quality of life and work productivity were achieved and sustained with upadacitinib in

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Adalimumab for induction of remission in Crohn's disease

Cited by 12 publications

References 47 publications

SAveRUNNER: A network-based algorithm for drug repurposing and its application to COVID-19

SAveRUNNER: A network-based algorithm for drug repurposing and its application to COVID-19

Adalimumab for induction of remission in patients with Crohn's disease: a systematic review and meta-analysis

Quality of Life and Work Productivity Improvements with Upadacitinib: Phase 2b Evidence from Patients with Moderate to Severe Crohn’s Disease

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