Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi in Psoriasis and Psoriatic Arthritis, 2017
The risk for developing PML after treatment with natalizumab, an anti-α4 integrin used for multiple sclerosis, has been estimated to be approximately 2 in 1000 for patients treated for more than 2 years. The unexpected development of PML in patients treated with natalizumab triggered its voluntary withdrawal from the market in February 2005, but it returned in July 2006 under Tysabri Outreach: Unified Commitment to Health (TOUCH) monitoring because there were not many effective alternatives for MS. However, in the case of psoriasis, until 2009, four cases were described within a cohort of 6000 patients who had received efalizumab for psoriasis (i.e., incidence less than that for natalizumab), but it lead to voluntary withdrawal of efalizumab in 2009 partly because psoriasis has alternative treatments, unlike MS. A newer α4β7 heterodimer-specific integrin inhibitor, vedolizumab, is under trial for IBD, which has shown promise, as no PML cases have so far been described, although it was predicted to have similar PML frequency as natalizumab. Unfortunately, vedolizumab is so far thought to be useful for gut inflammation but not joint or skin inflammation. Vedolizumab, AMG181, and so forth, target the integrin heterodimer α4β7, thus blocking their interaction with MAdCAM1 in mucosa. Inspired by the success of these molecules, similar heterodimer target approaches are being attempted for other integrins. A synthetic peptide (“peptide 3.1,” CKSTHDRLC) with specificity for the human arthritic synovium has been putatively identified in similar ways.
Information on level of drugs into breastmilk
Wendy Jones in Breastfeeding and Medication, 2018
Infliximab, adalimumab, and golimumab are monoclonal antibodies that inhibit the pro-inflammatory cytokine, tumour necrosis factor alpha. They should be used under specialist supervision. They are options for the treatment of severe active Crohn’s disease, following inadequate response to conventional therapies or in those who are intolerant of or have contra-indications to conventional therapy. Vedolizumab is recommended as a treatment option for moderate to severely active Crohn’s disease when therapy with adalimumab or infliximab is unsuccessful, is contra-indicated or not tolerated. Adalimumab and infliximab can be used as monotherapy or combined with an immunosuppressant although there is uncertainty about the comparative effectiveness and long-term side-effects of therapy.
Inflammatory Bowel Disease
Vincenzo Berghella in Maternal-Fetal Evidence Based Guidelines, 2022
Vedolizumab: This is a humanized monoclonal IgG1 antibody approved for use in CD. There is limited data to support the safety of vedolizumab use in pregnancy [96, 97]. Similar to natalizumab, there are concerns regarding effects on the neonatal immune system response. To alleviate these concerns, consideration can be given to administer the last dose 6–10 weeks before delivery [97]. While vedolizumab appears to be compatible with breastfeeding, data is very limited and warrants careful counseling [96, 97]. Pediatric or neonatology consultation can be offered to discuss vaccination risks.
Special considerations for biologic medications in pediatric ulcerative colitis
Published in Expert Opinion on Biological Therapy, 2020
Logan Jerger, Jeffrey S. Hyams
Given its effectiveness in adults with IBD, this medication has been used in pediatric patients, including both Crohn’s disease and UC. One multicenter, retrospective study evaluated its use in pediatric IBD, and when stratifying data for pediatric UC, 76% of patients were found to be in clinical remission based on PUCAI [48]. In both Crohn’s disease as well as UC, this study found that in the pediatric population, patients with colon-only disease had higher rates of remission at multiple time points during the study. An additional discussion point worth noting here is that anti-TNF-naïve patients had statistically significantly higher rates of remission (100% vs. 45%; p = 0.04). During the study period, safety was also illustrated with a lack of serious adverse events. The results were also evidenced by smaller studies as well, including those with prior anti-TNF-α failure [49,50]. From this literature, the use of vedolizumab, particularly in colonic disease, has been suggested as beneficial with limited side effects noted as well. It is also worth mentioning that limited data support its use in those not responding to anti-TNF-α biologic medications. However, controlled trial data are lacking and further studies are needed.
Safety of drugs used for the treatment of Crohn’s disease
Published in Expert Opinion on Drug Safety, 2019
Aviv Pudipeddi, Viraj Kariyawasam, Craig Haifer, Brandon Baraty, Sudarshan Paramsothy, Rupert WL Leong
With an increasing choice of biological agents in the treatment of IBD, the newer biological agents vedolizumab and ustekinumab appear to be safer options in comparison to anti-TNF drugs. The main adverse event from vedolizumab is an upper respiratory tract infection/nasopharyngitis, however, there appears to be no serious risk of opportunistic infections or malignancy from this medication. It also appears to be well tolerated in the elderly population. PML continues to be monitored closely in those prescribed vedolizumab but without a logical reason, and real-world data have not shown vedolizumab use to be a risk factor for the development of PML. Given that HIV infection increases the risk of PML, however, we suggest performing baseline HIV serological testing prior to starting vedolizumab in the rare event of PML being diagnosed later.
Higher vedolizumab serum levels do not increase the risk of adverse events in patients with inflammatory bowel disease
Published in Scandinavian Journal of Gastroenterology, 2020
Neil K. Sengupta, Ahmad Azizov, Smita Halder, Ted Xenodemetropoulos, David Armstrong, Frances Tse, John K. Marshall, Neeraj Narula
No study to date has investigated the relationship of adverse reactions with respect to vedolizumab serum concentrations. The landmark studies [3,4] and subsequent real-world cohorts [8,21] have reported rates of adverse events with vedolizumab at approximately 25–30% of users, consistent with our findings. Gut selective alpha integrin inhibitors such as vedolizumab are generally thought to have favourable safety profiles compared to TNFα inhibitors. However, they may be associated with risk of certain adverse events, such as nasopharyngitis and infectious colitis [22]. The rates of serious adverse events are also higher with treatment using vedolizumab than to placebo [3,4]. However, recent work from the VICTORY study has suggested that vedolizumab adverse events may be as low as 6 in 1000 infusions [23]. The present study identified no significant difference in adverse events between the higher serum level cohort and the lower serum level cohort, and provides further evidence supporting the safety profile of vedolizumab.
Related Knowledge Centers
- Monoclonal Antibody
- Ulcerative Colitis
- Crohn's Disease
- Integrin
- Lpam-1
- Peyer'S Patch
- Protein Dimer
- Integrin Alpha 4
- Integrin Beta 7
- Anti-Inflammatory