How Do Immunomodulators (DMARDs) Work?

Immunomodulators (DMARDs) belong to a class of medications known as disease-modifying anti-rheumatic drugs (DMARDs), which modify and slow down or halt the course of disease in many autoimmune and other inflammatory diseases and cancers.

Immunomodulators include synthetic compounds that are toxic to cancer cells, biologic monoclonal antibodies against specific antigens, and small molecule drugs that are capable of penetrating cells and altering their functions. Immunomodulators work in diverse ways to modify immune cell functions to control inflammation and tumor growth.

Some of how immunomodulator DMARDs suppress the immune system and prevent abnormal cell growth include the following:

• Inhibit the activation of T-lymphocytes, immune cells that attack specific antigens they perceive as foreign to the body.
• Block the activity of pro-inflammatory proteins released by immune cells, including:
  • Interleukin-1 alpha and beta mediate inflammatory responses such as fever.
  • Interleukin-6 has many functions such as activation of T-cells, induction of immunoglobulin (antibody) secretion, stimulation of immune response from the liver, and stimulation of blood cell proliferation and differentiation.
• Inhibit the division of cells by interfering with DNA and RNA synthesis.
• Prevent malignant cell growth by cross-linking DNA in tumor cells.
• Prevent T-cell proliferation and activation by inhibiting calcineurin, a key signaling enzyme.
• Prevent cell division and proliferation by inhibiting enzymes essential for nucleotide (DNA and RNA building blocks) synthesis.
• Inhibit enzymes known as Janus kinases (JAK) which transmit signals from the cell membrane within the cell, stimulating an immune response and blood cell formation.

Immunomodulators (DMARDs) may be administered through the following routes:

• Oral:
  • Tablets
  • Capsules
  • Solutions
• Injections:
  • Subcutaneous (SC) injection into the tissue under the skin
  • Intramuscular (IM) injection into the muscle
  • Intravenous (IV) injections or infusions into the vein
  • Intrathecal (IT) injections into the cerebrospinal fluid in the spinal canal

Immunomodulators (DMARDs) are used in the treatment of conditions that include the following:

FDA-approved:

• Rheumatoid arthritis, an autoimmune inflammatory disease that affects joints
• Psoriatic arthritis, a form of arthritis that develops in people with psoriasis, a skin condition
• Juvenile idiopathic arthritis, a form of arthritis that develops in children
• Juvenile idiopathic arthritis/vasculitis
• Systemic juvenile idiopathic arthritis
• Polyarticular juvenile idiopathic arthritis
• Cryopyrin-associated periodic syndromes (CAPS), a group of rare inherited diseases due to defect in the gene that codes for the protein cryopyrin, which includes:
  • Neonatal-onset multisystem inflammatory disease (NOMID) also known as a chronic infantile neurological, cutaneous and articular syndrome (CINCA)
• Deficiency of interleukin-1 receptor antagonist, a rare genetic condition that causes systemic inflammation
• Giant cell arteritis (inflammation of arteries)
• Kidney transplantation, to prevent transplant rejection
• Solid-organ transplant including liver, heart, and kidney, to prevent transplant rejection
• Nephrotic syndrome, a kidney disorder that causes excessive excretion of protein in the urine
• Systemic lupus erythematosus, an autoimmune disease
• Psoriasis
• Malignant diseases (cancers)
• Non-Hodgkin’s lymphoma
• Breast cancer
• Acute lymphoblastic leukemia
• Meningeal leukemia
• Osteosarcoma
• Squamous cell carcinoma of head and neck
• Gestational trophoblastic neoplasia, a rare form of tumor that develops during pregnancy
• Interstitial lung disease, a group of diseases that scar lungs
• Cytokine release syndrome, a systemic inflammatory response triggered by infections or certain drugs
• Ulcerative colitis

Off-label:

• Crohn’s disease, an inflammatory bowel disease
• Chronic refractory thrombocytopenic purpura, an autoimmune disorder that suppresses platelet production and destroys them
• Kidney transplantation, to prevent transplant rejection in children
• Solid-organ transplant including liver, heart, and kidney, to prevent transplant rejection in children
• Lupus nephritis, kidney inflammation caused by lupus
• Juvenile idiopathic arthritis/vasculitis in adults
• Systemic sclerosis, an autoimmune disease that hardens and tightens skin and connective tissue
• Ectopic pregnancy

Orphan:

• Diabetes mellitus type I
• Graft versus host disease, a complication after transplant in which the donor cells attack the host cells
• Still’s a disease, a rare form of arthritis
• Bronchiolitis obliterans, an inflammation of the small airways (bronchioles) in the lungs, caused by a viral infection
• Amyotrophic lateral sclerosis (ALS), a neuromuscular disease
• Traumatic brain injury
• Myasthenia gravis, a neuromuscular disease
• Ectopic pregnancy
• Proliferative vitreoretinopathy, a rare condition that causes scar tissue formation in the retina and can lead to vision loss

Emergency use authorization (EUA):

• COVID-19

Some of the most common side effects of immunomodulators (DMARDs) may include the following:

• Injection site reaction
• Arachnoiditis (inflammation of the arachnoid membrane around the spinal cord) with intrathecal administration
• Subacute toxicity with intrathecal administration (paralysis of extremities, cranial nerve palsy, seizure, or coma)
• Demyelinating encephalopathy (inflammation of brain and spinal cord that damages myelin, the protective sheath on nerve fibers) with cranial irradiation or other systemic chemotherapy
• Headache
• Nasopharyngitis (inflammation of nose and throat)
• Pharyngitis (throat inflammation)
• Ulcerative stomatitis (inflammation in the mouth)
• Glossitis (inflammation of the tongue)
• Gingivitis (inflammation of gums)
• Mucositis (inflammation of the mucous membranes of the digestive tract)
• Nausea
• Vomiting
• Abdominal discomfort
• Diarrhea
• Dyspepsia (indigestion)
• Anorexia (loss of appetite)
• Constipation
• Intestinal perforation
• Reddening of skin
• Infections
• Upper respiratory infection
• Arthralgia (joint pain)
• Leg cramps
• Pyrexia (fever)
• Leukopenia (low count of leukocytes, type of immune cells)
• Neutropenia (low count of neutrophils, type of immune cells)
• Thrombocytopenia (low platelet count in the blood)
• Tremor
• Paresthesia (skin prickling sensation)
• Nephrotoxicity (toxicity to the kidney)
• Nephropathy (kidney disease)
• Renal failure
• Hyperuricemia (excess uric acid in the blood)
• Azotemia (elevation of blood urea nitrogen [BUN] and serum creatinine levels)
• Hypertension (high blood pressure)
• Hirsutism (abnormal male pattern hair growth in women)
• Hypertrichosis (abnormally excessive hair growth in men/women)
• Female reproductive disorders
• Gum hyperplasia (overgrowth)
• Increase in triglyceride levels

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of immunomodulators (DMARDs) include:

• abatacept
• Actemra
• anakinra
• Azasan
• azathioprine
• cyclophosphamide
• cyclosporine
• Cytoxan
• Gengraf
• Imuran
• Kineret
• methotrexate
• Neoral
• Orencia
• Orencia ClickJect
• Otrexup
• Rasuvo
• RediTrex
• Sandimmune
• tocilizumab
• tofacitinib
• Trexall
• Xatmep
• Xeljanz
• Xeljanz XR