ATC Group: L04A Immunosuppressants

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.

Position of L04A in the ATC hierarchy

Level Code Title
1 L Antineoplastic and immunomodulating agents
2 L04 Immunosuppressants
3 L04A Immunosuppressants

Group L04A contents

Code Title
L04AA Selective immunosuppressants
L04AB Tumor necrosis factor alpha (TNF-α) inhibitors
L04AC Interleukin inhibitors
L04AD Calcineurin inhibitors
L04AE Sphingosine-1-phosphate (S1P) receptor modulators
L04AF Janus-associated kinase (JAK) inhibitors
L04AG Monoclonal antibodies
L04AH Mammalian target of rapamycin (mTOR) kinase inhibitors
L04AJ Complement inhibitors
L04AK
L04AX Other immunosuppressants

Active ingredients in L04A

Active Ingredient Description
Abatacept

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

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’.

Adalimumab

Adalimumab binds specifically to TNF and neutralizes the biological function of TNF by blocking its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of 0.1-0.2 nM).

Afelimomab

Afelimomab is an anti-TNFα monoclonal antibody. Administration of afelimomab reduces the concentration of interleukin-6 in patients with sepsis, but reduces mortality only marginally.

Alefacept

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

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.

Anakinra

Anakinra neutralises the biologic activity of interleukin-1α (IL-1α) and interleukin-1β (IL-1β) by competitively inhibiting their binding to interleukin-1 type I receptor (IL-1RI). Interleukin-1 (IL-1) is a pivotal pro-inflammatory cytokine mediating many cellular responses including those important in synovial inflammation.

Anifrolumab

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.

Antilymphocyte immunoglobulin

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

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

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

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.

Azathioprine

Azathioprine is a pro-drug of 6-mercaptopurine (6-MP). 6-MP is inactive but acts as a purine antagonist and requires cellular uptake and intracellular anabolism to thioguanine nucleotides (TGNs) for immunosuppression. The TGNs and other metabolites (e.g. 6-methyl-mecaptopurine ribonucleotides) inhibit de novo purine synthesis and purine nucleotide interconversions.

Baricitinib

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.

Basiliximab

Basiliximab is a murine/human chimeric monoclonal antibody (IgG1κ) that is directed against the interleukin-2 receptor α-chain (CD25 antigen), which is expressed on the surface of T-lymphocytes in response to antigenic challenge. Basiliximab specifically binds with high affinity (KD-value 0.1 nM) to the CD25 antigen on activated T-lymphocytes expressing the high affinity interleukin-2 receptor (IL-2R) and thereby prevents binding of interleukin-2, a critical signal for T-cell proliferation in the cellular immune response involved in allograft rejection.

Belatacept

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

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.

Belumosudil

Belumosudil is a serine/threonine kinase inhibitor indicated for the treatment of chronic graft-versus-host disease (chronic GVHD). Specifically, it is an inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2; ROCK-II). Belumosudil binds to and inhibits the serine/threonine kinase activity of ROCK2. This inhibits ROCK2-mediated signaling pathways which play major roles in pro- and anti-inflammatory immune cell responses.

Brodalumab

Brodalumab is a recombinant fully human monoclonal immunoglobulin IgG2 antibody that binds with high affinity to human IL-17RA and blocks the biological activities of the pro-inflammatory cytokines IL-17A, IL-17F, IL-17A/F heterodimer and IL-25, resulting in inhibition of the inflammation and clinical symptoms associated with psoriasis.

Canacinumab

Canacinumab is a human monoclonal anti-human interleukin-1 beta (IL-1 beta) antibody of the IgG1/κ isotype. Canacinumab binds with high affinity specifically to human IL-1 beta and neutralises the biological activity of human IL-1 beta by blocking its interaction with IL-1 receptors, thereby preventing IL-1 beta-induced gene activation and the production of inflammatory mediators.

Certolizumab pegol

Certolizumab pegol has a high affinity for human TNFα and binds with a dissociation constant (KD) of 90 pM. TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes. Certolizumab pegol was shown to neutralise membrane associated and soluble human TNFα in a dose-dependent manner. By inhibiting the action of TNFα, certolizumab pegol reduces inflammation and other symptoms in patients with rheumatoid arthritis.

Ciclosporin

Ciclosporin (also known as ciclosporin A) is a cyclic polypeptide immunomodulator with immunosuppressant properties. It has been shown to prolong survival of allogeneic transplants in animals and significantly improved graft survival in all types of solid organ transplantation in man. Ciclosporin has also been shown to have an anti-inflammatory effect.

Cladribine

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.

Daclizumab

Daclizumab beta is a humanised IgG1 monoclonal antibody that binds to CD25 (IL-2Rα), and prevents IL-2 binding to CD25, resulting in higher levels of IL-2 available for signalling through the intermediate-affinity IL-2 receptor. Key effects of this IL-2 pathway modulation potentially related to the therapeutic effects of daclizumab beta in MS include selective antagonism of activated T-cell responses, and expansion of immunoregulatory CD56bright natural killer (NK) cells, which have been shown to selectively decrease activated T-cells.

Darvadstrocel

Darvadstrocel contains expanded adipose stem cells (eASC), which exhibit immunomodulatory and anti-inflammatory effects at inflammation sites.

Deucravacitinib

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.

Dimethyl fumarate

The anti-inflammatory and immunomodulating effects of dimethyl fumarate and its metabolite monomethyl fumarate are not fully elucidated but are thought to be mainly due to the interaction with the intracellular reduced glutathione of cells directly involved in the pathogenesis of psoriasis. Their main activity is considered to be immunomodulatory, resulting in a shift in T helper cells (Th) from the Th1 and Th17 profile to a Th2 phenotype.

Eculizumab

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

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

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

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.

Etanercept

Etanercept is a competitive inhibitor of TNF binding to its cell surface receptors, and thereby inhibits the biological activity of TNF. The mechanism of action of etanercept is thought to be its competitive inhibition of TNF binding to cell surface TNFR, preventing TNF-mediated cellular responses by rendering TNF biologically inactive.

Etrasimod

Etrasimod is a sphingosine-1-phosphate (S1P) receptor modulator that binds to S1P receptors 1, 4 and 5 (S1P1,4,5) and is a balanced G-protein and beta-arrestin agonist at S1P1. Etrasimod has minimal activity on S1P3 and no activity on S1P2. Etrasimod partially and reversibly blocks the capacity of lymphocytes to egress from lymphoid organs, reducing the number of lymphocytes in peripheral blood thereby lowering the number of activated lymphocytes in the tissue. The mechanism by which etrasimod exerts therapeutic effects in ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into sites of inflammation.

Everolimus

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

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

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.

Golimumab

Golimumab is a human monoclonal antibody that forms high affinity, stable complexes with both the soluble and transmembrane bioactive forms of human TNF-α, which prevents the binding of TNF-α to its receptors.

Guselkumab

Guselkumab is a human IgG1λ monoclonal antibody (mAb) that binds selectively to the interleukin 23 (IL-23) protein with high specificity and affinity. IL-23, a regulatory cytokine, affects the differentiation, expansion, and survival of T cell subsets, (e.g., Th17 cells and Tc17 cells) and innate immune cell subsets, which represent sources of effector cytokines, including IL-17A, IL-17F and IL-22 that drive inflammatory disease. In humans, selective blockade of IL-23 was shown to normalize production of these cytokines.

Imlifidase

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.

Infliximab

Infliximab is a chimeric human-murine monoclonal antibody that binds with high affinity to both soluble and transmembrane forms of TNFα but not to lymphotoxin α (TNFβ).

Iptacopan

Iptacopan binds to Factor B of the alternative complement pathway and regulates the cleavage of C3, generation of downstream effectors, and the amplification of the terminal pathway.

Ixekizumab

Ixekizumab is an IgG4 monoclonal antibody that binds with high affinity (<3 pM) and specificity to interleukin 17A (both IL-17A and IL-17A/F). Elevated concentrations of IL-17A have been implicated in the pathogenesis of psoriasis by promoting keratinocyte proliferation and activation, as well as in the pathogenesis of psoriatic arthritis. Neutralisation of IL-17A by ixekizumab inhibits these actions.

Leflunomide

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.

Lenalidomide

The lenalidomide mechanism of action includes anti-neoplastic, anti-angiogenic, pro-erythropoietic, and immunomodulatory properties.

Methotrexate

Methotrexate (4-amino-10-methylfolic acid) is a folic acid antagonist which inhibits the reduction of folic acid and increase of tissue cells. Methotrexate enters the cell through an active transport mechanism of reduced folates. As a result of polyglutamation of methotrexate caused by the folylpolyglutamylate enzyme, the duration of the cytotoxic effect of the drug substance in the cell increases.

Mirikizumab

Mirikizumab is a humanised IgG4 monoclonal, anti-interleukin-23 (anti-IL-23) antibody that selectively binds to the p19 subunit of human IL-23 cytokine and inhibits its interaction with the IL-23 receptor. In humans, selective blockade of IL-23 was shown to normalise production of effector cytokines, including IL-17A, IL-17F and IL-22 that drive inflammatory disease.

Muromonab
Mycophenolate mofetil

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

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

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

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

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.

Peficitinib
Pegcetacoplan

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.

Pirfenidone

Pirfenidone attenuates fibroblast proliferation, production of fibrosis-associated proteins and cytokines, and the increased biosynthesis and accumulation of extracellular matrix in response to cytokine growth factors. Pirfenidone is indicated in adults for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF).

Pomalidomide

Pomalidomide has direct anti-myeloma tumoricidal activity, immunomodulatory activities and inhibits stromal cell support for multiple myeloma tumour cell growth. Pomalidomide in combination with bortezomib and dexamethasone is indicated in the treatment of adult patients with multiple myeloma.

Ponesimod

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

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).

Rilonacept

Rilonacept is a dimeric fusion protein which binds to and blocks the activity of the cytokine IL-1 and binds both IL-1β and IL-1α. Rilonacept is indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS) with severe symptoms.

Risankizumab

Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds with high affinity to the p19 subunit of human interleukin 23 (IL-23) cytokine and inhibits IL-23-dependent cell signalling and release of proinflammatory cytokines. Risankizumab is indicated for the treatment of moderate to severe plaque psoriasis.

Ritlecitinib

Ritlecitinib irreversibly and selectively inhibits Janus kinase (JAK) 3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) family by blocking the adenosine triphosphate (ATP) binding site. JAK3 and TEC family mediated signalling pathways are both involved in alopecia areata pathogenesis, although complete pathophysiology is still not understood.

Rozanolixizumab

Rozanolixizumab is a humanised IgG4 monoclonal antibody that decreases serum IgG concentration by inhibiting the binding of IgG to FcRn, a receptor that under physiological conditions protects IgG from intracellular degradation and recycles IgG back to the cell surface. By the same mechanism, rozanolixizumab decreases the concentration of pathogenic IgG autoantibodies associated with generalised myasthenia gravis (gMG).

Sarilumab

Sarilumab is a human monoclonal antibody (IgG1 subtype) that specifically binds to both soluble and membrane-bound IL-6 receptors (IL-6Rα), and inhibits IL-6-mediated signalling which involves ubiquitous signal-transducing glycoprotein 130 (gp130) and the Signal Transducer and Activator of Transcription-3 (STAT-3). In functional human cell-based assays, sarilumab was able to block the IL-6 signalling pathway, measured as STAT-3 inhibition, only in the presence of IL-6.

Satralizumab

Satralizumab is a recombinant humanised immunoglobuline G2 (IgG2) monoclonal antibody (mAb) that binds to soluble and membrane-bound human IL-6 receptor (IL-6R) and thereby prevents IL-6 downstream signalling through these receptors.

Secukinumab

Secukinumab is a fully human IgG1/κ monoclonal antibody that selectively binds to and neutralises the proinflammatory cytokine interleukin-17A (IL-17A). Treatment with secukinumab reduces erythema, induration and desquamation present in plaque psoriasis lesions.

Siltuximab

Siltuximab is a monoclonal antibody that forms high affinity, stable complexes with soluble bioactive forms of human IL-6. Siltuximab prevents the binding of human IL-6 to both soluble and membrane-bound IL-6 receptors (IL-6R), thus inhibiting the formation of the hexameric signaling complex with gp130 on the cell surface.

Siponimod

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

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.

Spesolimab

Spesolimab is a humanised antagonistic monoclonal immunoglobulin G1 (IgG1) antibody blocking human IL36R signalling. Binding of spesolimab to IL36R prevents the subsequent activation of IL36R by cognate ligands (IL36 α, β and γ) and downstream activation of pro-inflammatory pathways.

Sutimlimab

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.

Tacrolimus

Tacrolimus is a highly potent immunosuppressive agent. In particular, tacrolimus inhibits the formation of cytotoxic lymphocytes, which are mainly responsible for graft rejection. Tacrolimus suppresses T-cell activation and T-helper-cell dependent B-cell proliferation, as well as the formation of lymphokines (such as interleukins-2, -3, and γ-interferon) and the expression of the interleukin-2 receptor.

Teriflunomide

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.

Thalidomide

Thalidomide shows immunomodulatory, anti-inflammatory and potential anti-neoplastic activities. Thalidomide is also a non-barbiturate centrally active hypnotic sedative. It has no antibacterial effects.

Tildrakizumab

Tildrakizumab is a humanized IgG1/k monoclonal antibody that specifically binds to the p19 protein subunit of the interleukin-23 (IL-23) cytokine without binding to IL-12 and inhibits its interaction with the IL-23 receptor. Tildrakizumab inhibits the release of proinflammatory cytokines and chemokines.

Tocilizumab

Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R). IL-6 is involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, induction of hepatic acute phase protein synthesis and stimulation of haemopoiesis. IL-6 has been implicated in the pathogenesis of diseases including inflammatory diseases, osteoporosis and neoplasia.

Tofacitinib

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

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

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.

Ustekinumab

Ustekinumab is a fully human IgG1κ monoclonal antibody that binds with specificity to the shared p40 protein subunit of human cytokines interleukin (IL)-12 and IL-23. Ustekinumab inhibits the bioactivity of human IL-12 and IL-23 by preventing p40 from binding to the IL-12R1 receptor protein expressed on the surface of immune cells. Abnormal regulation of IL 12 and IL 23 has been associated with immune mediated diseases, such as psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis.

Vedolizumab

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).

Voclosporin

Voclosporin is a calcineurin-inhibitor immunosuppressant that inhibits calcineurin in a dose-dependent manner. The immunosuppressant activity results in inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens.

Zilucoplan

Zilucoplan is a 15 amino acid, synthetic macrocyclic peptide that inhibits the effects of the complement protein C5 through a dual mechanism of action. It specifically binds to C5, thereby inhibiting its cleavage by the C5 convertase to C5a and C5b, which results in a downregulation of the assembly and cytolytic activity of the membrane attack complex (MAC). Additionally, by binding to the C5b moiety of C5, zilucoplan sterically hinders binding of C5b to C6, which prevents the subsequent assembly and activity of the MAC, should any C5b be formed.

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DAILIPORT Prolonged-release hard capsule Medicines & Healthcare Products Regulatory Agency (GB) MPI, EU: SmPC
DEXIMUNE Capsule, soft Medicines & Healthcare Products Regulatory Agency (GB) MPI, EU: SmPC
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