How Do TNF Inhibitors (DMARDs) Work?

Tumor necrosis factor (TNF) inhibitors (DMARDs) belong to a class of medications known as disease-modifying anti-rheumatic drugs (DMARDs). TNF inhibitors are prescribed in the treatment of several autoimmune inflammatory disorders including arthritic, dermatologic and gastrointestinal diseases.

TNF inhibitors are lab-manufactured biologic products that suppress inflammation by blocking the activity of tumor necrosis factor-alpha (TNF-A), a protein (cytokine) that plays a central role in promoting persistent inflammation in autoimmune disorders.

TNF-A is produced by immune cells such as phagocytes to destroy the infection. TNF-A activity is normally well controlled in healthy people, but in autoimmune disorders, dysfunctional TNF-A causes persistent inflammation and tissue damage in many parts of the body including joints, skin, gastrointestinal tract, and other organs.

TNF-A binds to special molecules known as TNF receptors (TNFRI and TNFRII) in cell membranes to activate inflammatory signals and release other proinflammatory cytokines. TNF inhibitors bind to TNF-A and prevent its binding to the receptors and consequently, prevent the activation of inflammatory immune response.

TNF inhibitors (DMARDs) may be administered as subcutaneous injections in the tissue under the skin, or as intravenous injections or infusions to treat autoimmune inflammatory disorders that include:

FDA-approved:

• Rheumatoid arthritis (joint inflammation)
• Juvenile idiopathic arthritis (childhood arthritis with no known cause)
• Polyarticular juvenile idiopathic arthritis (arthritis in more than four joints)
• Spondyloarthritis (a family of arthritic conditions that affect the spine, other joints, bowel, skin, and eyes)
• Plaque psoriasis (skin condition with scaly lesions)
• Psoriatic arthritis (a complication of psoriasis)
• Ankylosing spondylitis (a type of arthritis that causes the vertebrae in the spine to fuse over time)
• Crohn’s disease (an inflammatory bowel disease)
• Pediatric Crohn’s disease
• Ulcerative colitis (an inflammatory bowel disease)
• Hidradenitis suppurativa (inflammation of hair follicles and sweat glands causing abscesses)
• Uveitis (inflammation of the uvea, the middle layer of the eye)

Orphan designation:

• Behcet’s disease (inflammation of blood vessels)
• Idiopathic pulmonary fibrosis (scarring of the lungs)

Side effects of TNF inhibitors (DMARDs) may include the following:

• Upper respiratory infections
• Non-upper respiratory infections
• Nasopharyngitis (inflammation of nose and throat)
• Pharyngitis (inflammation of the throat)
• Laryngitis (inflammation of the larynx/voice box)
• Rhinitis (inflammation of the nasal passage)
• Sinusitis (inflammation of the sinuses)
• Bronchitis (inflammation of the bronchial passage)
• Cough
• Development of antinuclear antibodies
• Headache
• Injection site reactions such as:
  • Erythema (redness)
  • Induration (hardening of the skin)
  • Pain
  • Bruising
  • Irritation
  • Paresthesia (prickling sensation)
• Infusion-related reactions
• Skin reactions such 
  • Rash
  • Urticaria (hives)
  • Pruritus (itching)
  • Skin exfoliation
  • Bullous reactions (blisters)
  • Linear IgA bullous dermatosis (an autoimmune skin disease)
  • Erythema multiforme (round lesions like a bullseye)
  • Cutaneous vasculitis (inflammation of blood vessels in the skin and the tissue beneath the skin)
  • Cutaneous lupus erythematosus (an autoimmune skin condition)
  • Subcutaneous nodule
  • Stevens-Johnson syndrome (a rare medical emergency with flu-like symptoms and a painful rash)
  • Lichenoid skin reaction (lichen planus-like eruptions)
  • Onset or worsening of psoriasis
  • Generalized exanthematous pustulosis (pustular eruptions)
  • Toxic epidermal necrolysis (a severe skin condition with widespread redness, skin cell death, and exfoliation which can lead to sepsis)
• Hypersensitivity reactions such as:
  • Alopecia (hair loss)
  • Angioedema (swelling in the tissue under the skin or mucous membranes)
  • Laryngeal/pharyngeal edema (swelling up of throat)
  • Bronchospasm
  • Respiratory tract allergic reaction
  • Anaphylaxis (serious allergic reaction)
  • Anaphylactic shock
• Increase in creatine phosphokinase (CPK)
• Development of antibodies to double-stranded DNA
• Elevated liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
• Increase in alkaline phosphatase levels in the blood
• Nausea
• Diarrhea
• Dyspepsia (indigestion)
• Abdominal pain
• Constipation
• Serious infections
• Opportunistic infections such as:
  • Tuberculosis
  • Atypical mycobacterial infection
  • Aspergillosis
  • Pneumocystis jiroveci pneumonia
  • Protozoal infections
• Viral infections such as influenza and herpes zoster
• Superficial fungal infections
• Candidiasis (Candida yeast infection)
• Bacterial infections
• Septic shock
• Bacterial arthritis
• Infective bursitis (inflammation of a bursa, fluid-filled sacs in joints)
• Abscess
• Urinary tract infection (UTI)
• Pyelonephritis (a type of kidney infection)
• Kidney/urinary disorder
• Hematuria (blood in the urine)
• Flulike syndrome
• Pyrexia (fever)
• Flushing
• Fatigue
• Back pain
• Arthralgia (joint pain)
• Chest pain
• Hyperlipidemia (high level of blood fats)
• Hypercholesterolemia (high cholesterol levels in the blood)
• Hypertension (high blood pressure)
• Cardiac disorder
• Pericardial effusion
• Congestive heart failure
• Myocardial ischemia (reduced blood supply to the heart muscles)
• Myocardial infarction (heart attack)
• Dyspnea (shortness of breath)
• Interstitial lung disease (a group of diseases such as pulmonary fibrosis that scar the lungs)
• Pulmonary embolism (blood clot in the lung)
• Lupus-like symptoms
• Blood disorders such as:
  • Leukopenia (low count of leukocyte immune cells)
  • Neutropenia (low blood count of neutrophil immune cells)
  • Agranulocytosis (low granulocytes, immune cells with granules)
  • Pancytopenia (low count of all types of blood cells)
  • Aplastic anemia (anemia due to reduced red cell production)
  • Thrombocytopenia (low platelet count)
  • Idiopathic thrombocytopenic purpura (easy bruising and bleeding due to thrombocytopenia)
  • Thrombotic thrombocytopenic purpura (a rare disorder that causes blood clots to form in small blood vessels)
• Lymphatic system disorder
• Lymphadenopathy (swollen lymph nodes)
• Bone fracture
• Hepatitis (liver inflammation)
• Jaundice
• Cholestasis (blockage of bile fluid flow)
• Liver failure
• Sarcoidosis (a disease that causes tiny collections of inflammatory cell growth)
• Benign neoplasms (tumors), cysts, and polyps
• Malignant growths including Merkel cell carcinoma and melanoma, types of skin cancer
• Cervical cancer
• Hepatosplenic T-cell lymphoma (a rare type of non-Hodgkin lymphoma)
• Leukemia (a type of blood and bone marrow cancer)
• Macrophage activation syndrome (excessive activation of immune cells such as macrophages and T-cells)
• Ocular disorder
• Transient vision loss
• Lagophthalmos (inability to fully close the eyelids)
• Optic neuritis (inflammation of the optic nerve)
• Uveitis (inflammation of the uvea, the middle layer of the eye)
• Scleritis (inflammation of sclera, the white layer of the eye)
• Convulsions
• Seizure
• Transverse myelitis (inflammation of the spinal cord)
• Demyelination (loss of myelin, the fatty tissue that protects nerve cells)
• Neurological disorders caused by demyelination, such as:
  • Guillain-Barre syndrome
  • Multiple sclerosis
  • Chronic inflammatory demyelinating polyneuropathy
  • Multifocal motor neuropathy
• Cerebrovascular accident
• Systemic vasculitis
• Deep vein thrombosis (DVT)
• Diverticulitis (inflammation of diverticula, small pouches that develop in the bowels) and an associated bowel perforation
• Appendicitis and associated perforations
• Pancreatitis (inflammation of the pancreas)
• Inflammatory bowel disease
• Anxiety
• Bipolar disorder
• Suicide attempt
• Menstrual disorder

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 TNF inhibitors (DMARDs) include:

• Abrilada
• adalimumab
• adalimumab-adaz
• adalimumab-adbm
• adalimumab-afzb
• adalimumab-atto
• adalimumab-bwwd
• adalimumab-fkjp
• Amjevita
• Avsola
• certolizumab pegol
• Cimzia
• Cyltezo
• Enbrel
• Erelzi
• etanercept
• etanercept-szzs
• etanercept-ykro
• Eticovo
• golimumab
• Hadlima
• Hulio
• Humira
• Hyrimoz
• Inflectra
• infliximab
• infliximab-abda
• infliximab-axxq
• infliximab-dyyb
• infliximab-qbtx
• Ixifi
• Remicade
• Renflexis
• Simponi
• Simponi Aria