From reversal agents to lipid-lowering agents, tailored antibodies target intrinsic molecules or pharmaceutical agents with very high specificity. They may be used diagnostically or therapeutically. Fab’s have been termed “the tiny tool to fight big diseases.”
— cardio-met (@cardiomet_CE) November 30, 2021
1) Welcome to a #Fab-ulous #tweetorial on some of the Fab fragment antibodies used in #cardiometabolic care. Their high specificity allows them to operate with minimal off-target effects, allowing for a range of diagnostic and therapeutic uses. I am @md_pollack. pic.twitter.com/T6iHsVw2z2
— cardio-met (@cardiomet_CE) December 1, 2021
3) This program is intended for healthcare professionals. Faculty disclosures are listed at https://t.co/gvXca4G9Xm. Earn credit from prior programs at https://t.co/U6Mo1oSwIh and also check out our companion site for more FREE CE/#CME credit at @ckd_ce.
— cardio-met (@cardiomet_CE) December 1, 2021
5) Antibodies are large proteins that are made by B cells of the adaptive immune system. While it is often thought that an antibody functions only as a whole molecule, some of the individual fragments of an antibody can also bind and neutralize antigens.
— cardio-met (@cardiomet_CE) December 1, 2021
7) The two arms of the Y are known as the “fragment antigen-binding” (Fab) portions and are each composed of 1 heavy chain & 1 light chain. The top half of each Fab fragment is the antigen-binding region of the antibody, and it is variable – meaning that it varies between …
— cardio-met (@cardiomet_CE) December 1, 2021
9) So the constant regions are identical in all IgG antibodies but differ between IgG & IgA antibodies. All antibodies are proteins known as gammaglobulins, or #immunoglobulins. The 5 classes of Ig’s–IgG, IgM, IgA, IgD, & IgE–differ according to their heavy chains.
— cardio-met (@cardiomet_CE) December 1, 2021
11) Not only are the specific for certain “antigens” with limited chances for off-target activity, but because they do not have the bulk of a whole antibody, fragments can also minimize other downstream effects on the immune system.
— cardio-met (@cardiomet_CE) December 1, 2021
13) Due to their prolonged circulating half-life and relative ease of production, all current clinically used therapeutic mAbs are IgGs. Their most common use is in the treatment of inflammatory diseases, such as #rheumatoid arthritis, #Crohn‘s disease, plaque #psoriasis …
— cardio-met (@cardiomet_CE) December 1, 2021
15) Fab fragments are also instrumental in oncology, where mAbs target tumor antigens and kill cancer cells. Their primary targets are growth factor receptors that are overexpressed in tumor cells, such as EGFR and HER2.
— cardio-met (@cardiomet_CE) December 1, 2021
17) mAbs & Fabs can also be conjugated with highly cytotoxic small molecules to make antibody-drug conjugates (#ADCs). ADCs can be used for targeted cancer therapy by conferring selective, sustained cytotoxic drug delivery to tumors, often more safely than with cytotoxins alone.
— cardio-met (@cardiomet_CE) December 1, 2021
19) Which of the following agents is NOT a mAB/Fab fragment antibody?
— cardio-met (@cardiomet_CE) December 1, 2021
21) Welcome back! You’re earning 0.5h CE/#CME as we learn about the value of #Fabs & MAbs in #cardiometabolic care. The answer from yesterday’s poll? The one that doesn’t end in “mab”–(b) eptifibatide.
— cardio-met (@cardiomet_CE) December 2, 2021
23) It’s not an exhaustive list but these are the most likely to encounter among our followership here at @cardiomet_CE. Follow along! @maciejbanach @JTLLERGO @edgarvlermamd @aayshacader @ToddVillinesMD @87HISHAM @mvaduganathan @heartmeds_org @CCPharmacists @CBallantyneMD
— cardio-met (@cardiomet_CE) December 2, 2021
25) Bentracimab appears to safely quickly effectively fully reverse the #antiplatelet effect of #ticagrelor and is currently in Phase 3 open-label study. What do they have in common? Both fully humanized #Fab fragments. Both show NO off-target activity.
— cardio-met (@cardiomet_CE) December 2, 2021
27) Both are being studied in clotting-impaired (i.e., anticoagulated or antiplatelet-treated) pre-procedural patients to promote #hemostasis and in patients with uncontrolled or life-threatening hemorrhage to support hemostasis.
— cardio-met (@cardiomet_CE) December 2, 2021
29) In Group A, among the patients who could be assessed, median time to the cessation of bleeding was 2.5h. In Group B, periprocedural hemostasis was assessed as normal in 93.4% of the patients. There was no prothrombotic effect noted.
— cardio-met (@cardiomet_CE) December 2, 2021
31) The data presented at #AHA21 were nearly all recorded in pre-procedural (not hemorrhaging) patients. Here are the key data from the presentation. The accepted article will be posted at https://t.co/c8v8HZKFx2 when production is complete. pic.twitter.com/ExuXRUqkbx
— cardio-met (@cardiomet_CE) December 2, 2021
33) For more on this, check out (and earn MORE free CE/#CME) https://t.co/jzWDHANASn. In FOXTROT (JAMA 2020;323(2):130-139), postop osocimab at 3 doses were noninferior to enoxaparin, & preop osocimab was superior to enox for incidence of VTE at 10 to 13 days postop. pic.twitter.com/kxP4o3JZS4
— cardio-met (@cardiomet_CE) December 2, 2021
35) Per label, digoxin immune Fab is used for digoxin toxicity when 1 of the following is present:
— cardio-met (@cardiomet_CE) December 2, 2021
(a) Hemodynamically unstable arrhythmia
(b) End organ damage
(c) digoxin level > 4 ng/ml if chronic ingestion
(d) level > 10 ng/ml if acute ingestion
(e) K+ > 5 mEq/L & symptomatic
37) Mark your answer and return tomorrow for the remaining two categories (antiplatelet, lipid-lowering) and your FREE CE/#CME! @MedTweetorials @CardioNerds @DrRaniKhatib @cardiogax @ethanjweiss @academiccme #FOAMed #FOAMcc
— cardio-met (@cardiomet_CE) December 2, 2021
39) While reversing the effects of digitalis, it will further ⬇️ serum K+ and could precipitate significant cardiac arrhythmias.
— cardio-met (@cardiomet_CE) December 3, 2021
So let's move on to one of the very first antibodies used in #cardiometabolic care: the #antiplatelet #abciximab.
41) Studies have shown abciximab to be effective in prevention of ischemic cardiac complications in patients undergoing #PCI and in patients with #unstableangina/#NSTEMI unresponsive to conventional therapy when scheduling PCI within 24 hours.
— cardio-met (@cardiomet_CE) December 3, 2021
43) So let's turn to our final category & the space within #cardiometabolic medicine where there is the most feverish activity re Fabs & mAbs: ⬇️lipid levels. Lipid-lowering therapy is a major cornerstone of medical treatment of CV disease in order to⬇️atherosclerosis risk.
— cardio-met (@cardiomet_CE) December 3, 2021
45) Two approved mAbs (evolocumab & alirocumab) are injected SQ biweekly or monthly & have demonstrated favorable safety profiles, in addition to efficacy in lowering LDL-C. That PCSK9 receptor is the antigen to the mAb. Binding of PCSK9 to the LDL receptor …
— cardio-met (@cardiomet_CE) December 3, 2021
47) … the expression on the plasma membrane is ⬆️d. This leads to an enhanced reduction of circulating LDL (see https://t.co/EYKCGIeRiC). Also, #PCSK9i are an alternative if statins are not tolerated due to adverse side effects. pic.twitter.com/gjqtH9E1ez
— cardio-met (@cardiomet_CE) December 3, 2021
49) ANGPTL3 slows the function of certain enzymes that break down fats in the body, so blocking it allows faster breakdown of fats that lead to ⬆️cholesterol. And core @cardiomet_CE faculty @ErinMichos spoke at #AHA21 about promising Phase 1 results for an ORAL PCSK9i!
— cardio-met (@cardiomet_CE) December 3, 2021
51) And that's it! You made it! Go to https://t.co/1Q3ZilVnfO and claim your FREE CE/#CME credit! And FOLLOW US here for the latest #cardiometabolic education from expert authors. Oh, and check out our companion site @ckd_ce for MORE opportunities to learn & earn! pic.twitter.com/I9TDtEFwCy
— cardio-met (@cardiomet_CE) December 3, 2021