CT-P13 subcutaneous infliximab in gastroenterology and rheumatology

Immunotherapy ◽  
2021 ◽  
Author(s):  
Mai Ahmed ◽  
Giulia Bankov ◽  
Dan Casey ◽  
Martin Edward Perry
Keyword(s):  
Rheumatoid Arthritis ◽  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Real World ◽  
Intravenous Therapy ◽  
Self Administration ◽  
Efficacy Data ◽  
Inflammatory Conditions ◽  
Therapy Choice ◽  
Cost Implications

The drug infliximab has been a key milestone in the treatment of inflammatory conditions such as Crohn's disease, ulcerative colitis, rheumatoid arthritis and the seronegative spondyloarthritides. Biosimilar drugs followed the originator, further improving access and diversity of therapy choice. Subcutaneous infliximab (CT-P13) holds potential for greater patient flexibility by self administration, reducing travel and hospital attendance for infusion, particularly relevant at a time of pandemic. We highlight the pharmacodynamic and pharmacokinetic basis of the subcutaneous device, clinical trials in rheumatology and gastroenterology and consider the safety and cost implications. Real-world switching data is required to confirm the efficacy data from clinical trials given the reduction in dosing flexibility compared with intravenous therapy.

scholarly journals Adverse events of special interest in clinical trials of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and psoriasis with 37 066 patient-years of tofacitinib exposure

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001595
Author(s):  
Gerd R Burmester ◽  
Peter Nash ◽  
Bruce E Sands ◽  
Kim Papp ◽  
Lori Stockert ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Special Interest ◽  
Phase 1 ◽  
Incidence Rates ◽  
Study Data ◽  
System Organ Class

ObjectivesTo analyse adverse events (AEs) of special interest across tofacitinib clinical programmes in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ulcerative colitis (UC) and psoriasis (PsO), and to determine whether the incidence rates (IRs; unique patients with events per 100 patient-years) of these events are consistent across diseases.MethodsThe analysis included data from patients exposed to ≥1 dose of tofacitinib in phase 1, 2, 3 or 3b/4 clinical trials and long-term extension (LTE) studies (38 trials) in RA (23 trials), PsA (3 trials), UC (5 trials) and PsO (7 trials). All studies were completed by or before July 2019, except for one ongoing UC LTE study (data cut-off May 2019). IRs were obtained for AEs of special interest.Results13 567 patients were included in the analysis (RA: n=7964; PsA: n=783; UC: n=1157; PsO: n=3663), representing 37 066 patient-years of exposure. Maximum duration of exposure was 10.5 years (RA). AEs within the ‘infections and infestations’ System Organ Class were the most common in all diseases. Among AEs of special interest, IRs were highest for herpes zoster (non-serious and serious; 3.6, 1.8, 3.5 and 2.4 for RA, PsA, UC and PsO, respectively) and serious infections (2.5, 1.2, 1.7 and 1.3 for RA, PsA, UC and PsO, respectively). Age-adjusted and sex-adjusted mortality ratios (weighted for country) were ≤0.2 across cohorts.ConclusionsThe tofacitinib safety profile in this analysis was generally consistent across diseases and with longer term follow-up compared with previous analyses.

scholarly journals A Comparison of the Randomized Clinical Trial Efficacy and Real-World Effectiveness of Tofacitinib for the Treatment of Inflammatory Bowel Disease: A Cohort Study

2019 ◽  
Author(s):  
Vivek A. Rudrapatna ◽  
Benjamin S. Glicksberg ◽  
Atul J. Butte
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Controlled Trials ◽  
Real World Data ◽  
Eligibility Criteria ◽  
Primary Endpoints ◽  
Three Phase

AbstractBackgroundReal-world data are receiving attention from regulators, biopharmaceuticals and payors as a potential source of clinical evidence. However, the suitability of these data to produce evidence commensurate with randomized controlled trials (RCTs) and the best practices in their use remain unclear. We sought to compare the real-world effectiveness of Tofacitinib in the treatment of IBD against efficacy rates published by corresponding RCTs.MethodsElectronic health records at the University of California, San Francisco (UCSF) were queried and reviewed to identify 86 Tofacitinib-treated IBD patients through 4/2019. The primary endpoint was treatment effectiveness. This was measured by time-to-treatment-discontinuation and by the primary endpoints of RCTs in Ulcerative Colitis (UC) and Crohn’s Disease (CD). Endpoints were measured and analyzed following a previously published protocol and analysis plan.Findings86 patients (68 with UC, 18 with CD) initiated Tofacitinib for IBD treatment. Most of the data needed to calculate baseline and follow-up disease activity indices were documented within the EHR(77% for UC, 91% for CD). Baseline characteristics of the UCSF and RCT cohorts were similar, except for a longer disease duration and 100% treatment failure of Tumor Necrosis Factor inhibitors in the former. None of the UCSF cohort would have met the RCT eligibility criteria due to multiple reasons.The rate of achieving the RCT primary endpoints were highly similar to the published rates for both UC(16%, P=0·5) and CD (38%, P=0·8). However, treatment persistence was substantially higher: 69% for UC (week 52) and 75% for CD (week 26).InterpretationAn analysis of routinely collected clinical data can reproduce published Tofacitinib efficacy rates, but also indicates far greater treatment durability than suggested by RCTs including possible benefit in CD. These results underscore the value of real-world studies to complement RCTs.FundingThe National Institutes of Health and UCSF Bakar InstituteResearch in ContextEvidence before this studyTofacitinib is the most recently approved treatment for Ulcerative Colitis. Data related to treatment efficacy for either IBD subtype is generally limited, whether from controlled trials or real-world studies. A search of clinicaltrials.gov was performed in January 2019 for completed phase 2 or 3, interventional, placebo-controlled clinical trials matching the terms “Crohn’s Disease” OR “Ulcerative Colitis” in the conditions field, and matching “Placebo” AND “Tofacitinib” OR “CP-690,550”) in the Interventions field. We identified three Phase 3 trials for UC (OCTAVE trials, all initially reported in a single article in 2016) and three Phase 2 trials of CD (two published in the same article in 2017, one reported in 2014). The Phase 3 UC trials reported 57·6% pooled clinical response rate in the Tofacitinib-assigned groups after 8 weeks (induction), and a 37·5% pooled remission rate among eligible induction trial responders in the Tofacitinib-assigned groups at 52 weeks. The 2017 CD trial reported a 70·8% pooled rate of response or remission in the Tofacitinib-assigned groups after 8 weeks, and a 47·6% pooled rate of response or remission among enrolled induction-trial responders at 26 weeks. A bias assessment of both UC and CD trials indicated a high risk of attrition bias and unclear risk of bias related to conflicts of interest. We also performed a search of pubmed.gov in January 2019 using search terms (“Colitis” OR “Crohn’s”) AND (“Tofacitinib” OR “CP-690,550”) OR “real-world” to identify cohort studies of Tofacitinib efficacy in routine clinical practice. No studies meeting these criteria were identified.Added value of this studyThis is one of the early studies to closely compare the results of clinical trials with the continuously-updated data captured in the electronic health records, and the very the first to assess the efficacy-effectiveness gap for Tofacitinib. We found that none of the patients treated at our center thus far would have qualified for the clinical trial based on published eligibility criteria. We found that the drug appeared to perform similarly to its efficacy when using the endpoints reported in clinical trials, but treatment persistence was significantly greater than would have been expected from the reported trial outcomes: 69% for UC at week 52 and 75% for CD at week 26.Implications of all the available evidenceTofacitinib is an effective treatment for the Ulcerative colitis and may be efficacious for Crohn’s disease. Controlled trials may not be representative of real-world cohorts, may not be optimally designed to identify efficacious drugs, and may not accurately predict patterns of use in clinical practice. Further studies using real-world data as well as methods to enable their proper use are needed to confirm and continuously monitor the efficacy and safety of drugs, both for on- and off-label use.

Salazopyrin en-tabs: an enteric-coated case that is hard to take

1987 ◽  
Vol 25 (14) ◽  
pp. 53.2-55
Keyword(s):  
Rheumatoid Arthritis ◽  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Enteric Coating ◽  
Disease Modifying ◽  
Enteric Coated ◽  
Established Treatment

Sulphasalazine (Salazopyrin - Pharmacia) has been an established treatment for ulcerative colitis (UC) for over 20 years. More recently its value as a disease-modifying drug in rheumatoid arthritis (RA) has become recognised again.1 All the clinical trials of the drug in RA have employed enteric-coated Salazopyrin EN-tabs rather than the plain tablets usually used in UC. The manufacturer emphasises that only this preparation (and not the plain tablets) ‘is indicated and approved for use in RA’. Why is the enteric coating essential in the treatment of RA but not in ulcerative colitis?

Vitamin B6 and immunity

2007 ◽  
Vol 269 ◽  
pp. 1-3
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Clinical Trials ◽  
Hiv Infection ◽  
Critically Ill ◽  
Vitamin B6 ◽  
Autoimmune Disorders ◽  
Vitamin B ◽  
Inflammatory Conditions

In a nutshellVitamin B6 levels are lower in inflammatory conditions and levels are linked with immune response, for example in the critically ill, in autoimmune disorders (such as rheumatoid arthritis) and possibly in HIV infection.As yet there have been too few clinical trials to tell whether there are specific indications to give B6 supplements in these conditions.

scholarly journals Update on the Safety Profile of Tofacitinib in Rheumatoid Arthritis from Clinical Trials to Real-World Studies: A Narrative Review

2020 ◽  
Author(s):  
Jose María Álvaro-Gracia ◽  
Jose Francisco García-Llorente ◽  
Mónica Valderrama ◽  
Susana Gomez ◽  
Maria Montoro
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Real World ◽  
Safety Profile ◽  
Narrative Review

Real-World Effectiveness and Safety of Tofacitinib in Patients With Ulcerative Colitis: Systematic Review With Meta-Analysis

2021 ◽  
Author(s):  
Carlos Taxonera ◽  
David Olivares ◽  
Cristina Alba
Keyword(s):  
Systematic Review ◽  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Real World ◽  
Meta Analysis ◽  
Mucosal Healing ◽  
Incidence Rates ◽  
Serious Adverse Events ◽  
The Real ◽  
Rate Of Response

Abstract Background Knowledge of the real-world effectiveness and safety of tofacitinib for ulcerative colitis (UC) is relevant to confirm the benefit observed in clinical trials. Methods This systematic review and meta-analysis evaluated the real-world effectiveness of tofacitinib for moderate to severely active UC. The primary outcome was clinical remission evaluated at week 8, weeks 12 to 16, and month 6. Secondary outcomes were response, corticosteroid-free remission, mucosal healing, colectomy, and safety. Results Seventeen studies with a total of 1162 patients with UC were included. Remission (11 studies) was achieved in 34.7% of patients at week 8 (95% confidence interval [CI], 24.4%-45.1%), 47% at weeks 12 to 16 (95% CI, 40.3%-53.6%), and 38.3% at month 6 (95% CI, 29.2%-47.5%) at month 6 duplicated. Response was achieved in 62.1%, 64.2%, 50.8%, and 41.8% of patients at week 8, weeks 12 to 16, month 6, and month 12, respectively. Corticosteroid-free remission (5 studies) was achieved in 38.4%, 44.3%, 33.6%, and 31% of patients at week 8, weeks 12 to 16, month 6, and month 12, respectively. Mucosal healing was achieved in 48.3% and 45.3% of patients at week 8 and weeks 12 to 16, respectively. Patients who were biologic-naïve (11.6%) had a significantly higher rate of response at week 8 (1.38; 95% CI, 1.03-1.84). The incidence rates of serious adverse events and herpes zoster was 8.9 and 6.9 per 100 patient-years, respectively. Conclusions This meta-analysis of real-world studies confirms the effectiveness of tofacitinib in a highly refractory population of patients with moderate to severely active UC. Tofacitinib showed an acceptable safety profile. These findings were consistent with clinical trials and further support the use of tofacitinib in UC.

scholarly journals Rheumatoid Arthritis Real-world Management Over 20 Years

2021 ◽  
pp. jrheum.201189
Author(s):  
Elena Nikiphorou ◽  
Fowzia Ibrahim ◽  
David L. Scott
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Cohort Studies ◽  
Prospective Study ◽  
Real World ◽  
Observational Studies ◽  
Patient Management ◽  
Routine Practice ◽  
Prospective Cohort Studies ◽  
A Prospective Study

Clinical trials show which treatments improve rheumatoid arthritis (RA), whereas observational studies show how patients are managed in routine practice. Prospective cohort studies give the most detailed information about what happens to patients, but being a part of a prospective study influences patient management because patients are no longer routine cases.

scholarly journals Real-world experience with tofacitinib in ulcerative colitis: a systematic review and meta-analysis

2021 ◽  
Vol 14 ◽  
pp. 175628482110640
Author(s):  
Laura A. Lucaciu ◽  
Nathan Constantine-Cooke ◽  
Nikolas Plevris ◽  
Spyros Siakavellas ◽  
Lauranne A.A.P. Derikx ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Clinical Response ◽  
Real World ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Safety Data ◽  
Janus Kinase ◽  
Random Effects Models

Background and aims: Tofacitinib is a Janus kinase inhibitor (JAKi) recently approved for the treatment of moderate to severe ulcerative colitis (UC) based on robust efficacy and safety data derived from OCTAVE clinical trials. Evidence on the outcomes of tofacitinib therapy in real-world UC patients is needed, as a number of these patients would be deemed ineligible for clinical trials. We have therefore summarised data derived from observational, real-world evidence (RWE) studies on the effectiveness and safety of tofacitinib in moderate to severe UC patients. Methods: We searched the PubMed, EMBASE, Scopus, Web of Science and Cochrane databases for observational studies on the use of tofacitinib in UC patients, published between 30 May 2018 and 24 January 2021. Pooled induction (8–14 weeks) and maintenance (16–26 weeks) clinical response and remission rates were calculated, as well as the proportion of reported adverse events using random effects models. Results: Nine studies were included, comprising 830 patients, of which 81% were previously treated with anti-tumour necrosis factor (TNF) and 57% with vedolizumab. Induction of clinical response and remission were achieved in 51% (95% confidence interval, 41–60%) and 37% (26–45%) of patients, after a median follow-up of 8 weeks. At the end of a median follow-up of 24 weeks, maintenance of clinical response and remission were met in 40% (31–50%) and 29% (23–36%) of patients, respectively. Thirty-two percent of the patients had at least one adverse event, the most commonly reported being mild infection (13%) and worsening of UC, requiring colectomy (13%). A third of the patients (35%) discontinued tofacitinib, most frequently due to primary non-response (51%). Conclusion: Tofacitinib is a safe and effective therapy in real-world UC patients, as previously reported by clinical trials.

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