The World Health Organization's ATC classification organizes medical drugs based on therapeutic properties, chemical composition, and anatomy. It helps make essential medicines readily available globally and is widely used in the pharmaceutical industry.
Abatacept is a fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G1 (IgG1). Abatacept selectively modulates a key costimulatory signal required for full activation of T lymphocytes expressing CD28.
Abetimus is a selective immunosuppressive agent (a compound that selectively dampens down the immune system). Most patients with SLE have antibodies in their blood that are directed against double-stranded DNA (deoxyribonucleic acid). These antibodies are thought to be linked to the development of lupus kidney disease. Abetimus is a small piece of double-stranded DNA that has been designed to reduce circulating levels of these antibodies. When Abetimus is injected, the levels of these antibodies in the blood are lowered and this is expected to help reduce the patient’s likelihood of experiencing a ‘flare’.
Alefacept interferes with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Activation of T lymphocytes involving the interaction between LFA-3 on antigen-presenting cells and CD2 on T lymphocytes plays a role in the pathophysiology of chronic plaque psoriasis. Also causes a reduction in subsets of CD2+ T lymphocytes as well as CD4+ and CD8+ T lymphocytes.
Alemtuzumab is a genetically engineered humanised IgG1 kappa monoclonal antibody specific for a 21-28 kD lymphocyte cell surface glycoprotein (CD52) expressed primarily on the surface of normal and malignant peripheral blood B and T cell lymphocytes. Alemtuzumab acts through antibody-dependent cellular cytolysis and complement-mediated lysis following cell surface binding to CD52, a cell surface antigen present at high levels on T (CD3+) and B (CD19+) lymphocytes, and at lower levels on natural killer cells, monocytes, and macrophages.
Anifrolumab is a human immunoglobulin G1 kappa monoclonal antibody that binds to subunit 1 of the type I interferon receptor (IFNAR1) with high specificity and affinity. This binding inhibits type I IFN signalling thereby blocking the biologic activity of type I IFNs. Inhibition of type I IFN blocks plasma cell differentiation and normalises peripheral T-cell subsets, restoring the balance between adaptive and innate immunity that is dysregulated in SLE.
Equine anti-thymocyte globulin is composed of purified gamma globulin containing primarily IgG against human thymus lymphocytes. It is formed by inoculating a horse with an antigen (human thymoyctes) which then induces the horse immune system’s B-lymphocytes to produce IgG immunoglobulins specific for that antigen. The result is polyclonal IgG that is then purified from the horse’s serum to produce a usable drug product that can be used for immunosuppression. Although the exact mechanism of action is unknown, equine anti-thymocyte globulin targets a variety of immune system proteins including lymphocyte surface proteins, granulocytes, platelets, bone marrow cells, and other cell types. Equine ATG is currently indicated for the suppression of the immune system to prevent renal transplant rejection and in the treatment of aplastic anemia. Induction of T cell apoptosis and resulting T-cell lymphopenia found in vivo is credited for its therapeutic effect in these conditions.
There are currently various ATG products available, which differ in the source of inoculated animal (rabbit, horse, or pig) and in the type of antigen product used to produce immunoglobulin (thymocytes, peripheral T cells, etc.).
Antithymocyte immunoglobulin is a selective immunosuppressive agent mostly acting on T lymphocytes. Antithymocyte immunoglobulin is used for the prevention and treatment of graft rejection after solid organ transplantation, usually in combination with other immunosuppressive drugs.
Apremilast, an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4), works intracellularly to modulate a network of pro-inflammatory and anti-inflammatory mediators. PDE4 is a cyclic adenosine monophosphate (cAMP)-specific PDE and the dominant PDE in inflammatory cells.
Avacopan is a selective antagonist of the human complement 5a receptor (C5aR1 or CD88) and competitively inhibits the interaction between C5aR1 and the anaphylatoxin C5a. The specific and selective blockade of C5aR1 by avacopan reduces the pro-inflammatory effects of C5a, which include neutrophil activation, migration, and adherence to sites of small blood vessel inflammation, vascular endothelial cell retraction and permeability.
Baricitinib is a selective and reversible inhibitor of Janus kinase (JAK)1 and JAK2. In isolated enzyme assays, baricitinib inhibited the activities of JAK1, JAK2, Tyrosine Kinase 2 and JAK3 with IC50 values of 5.9, 5.7, 53 and >400 nM, respectively. Janus kinases (JAKs) are enzymes that transduce intracellular signals from cell surface receptors for a number of cytokines and growth factors involved in haematopoiesis, inflammation and immune function.
Belatacept, a modified form of CTLA4-Ig, binds CD80 and CD86 more avidly than the parent CTLA4-Ig molecule from which it is derived. This increased avidity provides a level of immunosuppression that is necessary for preventing immune-mediated allograft failure and dysfunction. Belatacept blocks CD28 mediated co-stimulation of T cells inhibiting their activation.
Belimumab is a human IgG1λ monoclonal antibody specific for soluble human B Lymphocyte Stimulator protein (BLyS, also referred to as BAFF and TNFSF13B). Belimumab blocks the binding of soluble BLyS, a B cell survival factor, to its receptors on B cells. Belimumab by binding BLyS inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.
Cladribine is a nucleoside analogue of deoxyadenosine. In resting cells cladribine causes DNA single-strand breaks, rapid nicotinamide adenine dinucleotide consumption, ATP depletion and cell death.
Deucravacitinib selectively inhibits the TYK2 enzyme (TYK2 belongs to the JAK family). TYK2 mediates signalling of interleukin-23 (IL-23), interleukin-12 (IL-12), and type I interferons (IFN), which are naturally occurring cytokines involved in inflammatory and immune responses. Deucravacitinib inhibits the release of proinflammatory cytokines and chemokines.
Eculizumab is a monoclonal antibody, a terminal complement inhibitor that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9. Eculizumab preserves the early components of complement activation that are essential for opsonization of microorganisms and clearance of immune complexes.
Efalizumab is a recombinant humanized monoclonal antibody that binds specifically to the CD11a subunit of LFA-1 (lymphocyte function-associated antigen-1), a leukocyte cell surface protein. By this mechanism, efalizumab inhibits the binding of LFA-1 to ICAM-1, which interferes with T lymphocytes adhesion to other cell types. By preventing LFA-1/ICAM binding, efalizumab may alleviate signs and symptoms of psoriasis by inhibiting several stages in the immunologic cascade.
Efgartigimod alfa is a human IgG1 antibody fragment engineered for increased affinity to the neonatal Fc Receptor (FcRn). Efgartigimod alfa binds to FcRn, resulting in a reduction in the levels of circulating IgG including pathogenic IgG autoantibodies. Efgartigimod alfa does not affect the levels of other immunoglobulins (IgA, IgD, IgE or IgM), or those of albumin.
Emapalumab is a monoclonal antibody that binds to and neutralizes interferon gamma (IFNγ). Nonclinical data suggest that IFNγ plays a pivotal role in the pathogenesis of HLH by being hypersecreted.
Everolimus is a selective mTOR (mammalian target of rapamycin) inhibitor. mTOR is a key serine-threonine kinase, the activity of which is known to be upregulated in a number of human cancers.
Filgotinib is an adenosine triphosphate (ATP)-competitive and reversible inhibitor of the JAK family. Within the signalling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs) which modulate intracellular activity including gene expression. Filgotinib modulates these signalling pathways by preventing the phosphorylation and activation of STATs. Filgotinib is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients.
Fingolimod is a sphingosine 1-phosphate receptor modulator. Fingolimod is metabolised by sphingosine kinase to the active metabolite fingolimod phosphate. By acting as a functional antagonist of S1P receptors on lymphocytes, fingolimod phosphate blocks the capacity of lymphocytes to egress from lymph nodes, causing a redistribution, rather than depletion, of lymphocytes.
Imlifidase is a cysteine protease derived from the immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that cleaves the heavy chains of all human IgG subclasses but no other immunoglobulins. The cleavage of IgG leads to elimination of Fc-dependent effector functions, including CDC and antibody-dependent cell-mediated cytotoxicity (ADCC). By cleaving all IgG, imlifidase reduces the level of DSA, thus enabling transplantation.
Leflunomide is a disease-modifying anti-rheumatic agent with antiproliferative properties. A771726, the active metabolite of leflunomide, inhibits the human enzyme dihydroorotate dehydrogenase (DHODH) and exhibits antiproliferative activity.
Mycophenolate mofetil is the 2-morpholinoethyl ester of mycophenolic acid (MPA). MPA is a potent, selective, uncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase, and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA.
Mycophenolic acid is a potent, selective, uncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase, and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Mycophenolic acid has more potent cytostatic effects on lymphocytes than on other cells and is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute transplant rejection in adult patients receiving allogeneic renal transplants.
Natalizumab is a selective adhesion-molecule inhibitor and binds to the α4-subunit of human integrins, which is highly expressed on the surface of all leukocytes, with the exception of neutrophils.
Ocrelizumab is a recombinant humanised monoclonal antibody that selectively targets CD20-expressing B cells. The precise mechanisms through which ocrelizumab exerts its therapeutic clinical effects in MS is presumed to involve immunomodulation through the reduction in the number and function of CD20-expressing B cells. Following cell surface binding, ocrelizumab selectively depletes CD20-expressing B cells through antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis. The capacity of B-cell reconstitution and preexisting humoral immunity are preserved.
Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator, which binds selectively to sphingosine 1-phosphate receptor subtypes 1 and 5. Ozanimod causes lymphocyte retention in lymphoid tissues.
Pegcetacoplan is a symmetrical molecule comprised of two identical pentadecapeptides covalently bound to the ends of a linear 40-kDa PEG molecule. The peptide moieties bind to complement C3 and exert a broad inhibition of the complement cascade. The 40-kDa PEG moiety imparts improved solubility and longer residence time in the body after administration of the medicinal product. It is indicated in the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who are anaemic after treatment with a C5 inhibitor.
Ponesimod is a sphingosine 1-phosphate (S1P) receptor 1 modulator. Ponesimod binds with high affinity to S1P receptor 1 located on lymphocytes. It blocks the capacity of lymphocytes to egress from lymph nodes reducing the number of lymphocytes in peripheral blood. The mechanism by which it exerts therapeutic effects in multiple sclerosis may involve reduction of lymphocyte migration into the central nervous system.
Ravulizumab is a monoclonal antibody IgG2/4K that specifically binds to the complement protein C5, thereby inhibiting its cleavage to C5a (the proinflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex [C5b-9]) and preventing the generation of the C5b-9. Ravulizumab preserves the early components of complement activation that are essential for opsonisation of microorganisms and clearance of immune complexes. It is indicated in the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH).
Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. By acting as a functional antagonist on S1P1 receptors on lymphocytes, siponimod prevents egress from lymph nodes. This reduces the recirculation of T cells into the central nervous system (CNS) to limit central inflammation. Siponimod is indicated for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease.
Sirolimus inhibits T-cell activation induced by most stimuli, by blocking calcium-dependent and calcium-independent intracellular signal transduction. Studies demonstrated that its effects are mediated by a mechanism that is different from that of ciclosporin, tacrolimus, and other immunosuppressive agents.
Sutimlimab is an IgG, subclass 4 (IgG4) monoclonal antibody (mAb) that inhibits the classical pathway (CP) and specifically binds to complement protein component 1, s subcomponent (C1s), a serine protease that cleaves C4. The activities of the lectin and alternative complement pathways are not inhibited by sutimlimab. Inhibition of the classical complement pathway at the level of C1s prevents deposition of complement opsonins on the surface of red blood cells, resulting in inhibition of haemolysis in patients with CAD.
Teriflunomide is an immunomodulatory agent with anti-inflammatory properties that selectively and reversibly inhibits the mitochondrial enzyme dihydroorotate dehydrogenase (DHO-DH), required for the de novo pyrimidine synthesis. As a consequence teriflunomide reduces the proliferation of dividing cells that need de novo synthesis of pyrimidine to expand. The exact mechanism by which teriflunomide exerts its therapeutic effect in MS is not fully understood, but this is mediated by a reduced number of lymphocytes.
Tofacitinib is a potent, selective inhibitor of the JAK family. In human cells, tofacitinib preferentially inhibits signalling by heterodimeric cytokine receptors that associate with JAK3 and/or JAK1. Inhibition of JAK1 and JAK3 by tofacitinib attenuates signalling of interleukins and type I and type II interferons, which will result in modulation of the immune and inflammatory response.
Ublituximab is a chimeric monoclonal antibody that selectively targets CD20-expressing cells. CD20 is a cell surface antigen found on pre-B cells, mature and memory B cells but not expressed on lymphoid stem cells and plasma cells. The binding of ublituximab to CD20 induces lysis of CD20+ B cells.
Upadacitinib is a selective and reversible JAK inhibitor. In human cellular assays, upadacitinib preferentially inhibits signalling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2. It is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients.
Vedolizumab is a gut-selective immunosuppressive biologic. It is a humanised monoclonal antibody that binds specifically to the α4β7 integrin, which is preferentially expressed on gut homing T helper lymphocytes. By binding to α4β7 on certain lymphocytes, vedolizumab inhibits adhesion of these cells to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), but not to vascular cell adhesion molecule-1 (VCAM-1).