How Do Other DMARDs Work?

Other disease-modifying antirheumatic drugs (DMARDs) are medications that are not categorized into any of the specific classes of DMARDs. Each of the other DMARDs works in unique ways and are used in the prevention and treatment of malaria, autoimmune inflammatory conditions including rheumatoid arthritis, lupus, and ulcerative colitis, and certain blood cancers.

The medications that are grouped under other DMARDs include:

Hydroxychloroquine sulfate (HCQ):

Hydroxychloroquine sulfate is a weak base, a chemical compound that increases pH and neutralizes the acid. The precise mechanism of HCQ is not known, but it is believed to accumulate and raise the pH within the cells of Plasmodium, the malarial parasite, and prevent its ability to draw its nutrition from red blood cells and grow.

In inflammatory conditions, HCQ is thought to interfere with antigen processing by immune cells and activation of killer T-cells, which results in downregulation of inflammation. HCQ was initially granted emergency use authorization (EUA) for COVID-19, but the FDA has since revoked it based on emerging data that HCQ is unlikely to be effective for COVID.

Leflunomide:

Leflunomide is an immunomodulatory drug that reduces inflammation in rheumatoid arthritis by preventing the expansion of activated and autoimmune lymphocytes. Leflunomide inhibits the synthesis of pyrimidine nucleotide, a chemical compound essential for DNA and RNA synthesis in the lymphocytes that are activated during inflammation.

Rituximab:

Rituximab is a lab-manufactured humanized monoclonal antibody used in the treatment of certain types of blood cancers and autoimmune diseases that involve lymphocytes (B-cells). B-cells are part of the acquired immune system and produce antibodies, secrete inflammatory proteins (cytokines), and present antigens that activate inflammation.

B-cells grow uncontrolled in lymphomas, and in autoimmune diseases produce autoantibodies that attack the body’s cells. Rituximab is a monoclonal antibody that induces the immune system to destroy the aberrant B-cells. Rituximab binds to CD-20, an antigen expressed in B-cell membranes, and marks the B-cells for destruction by killer T-cells.

Sulfasalazine:

Sulfasalazine is a drug used to treat rheumatoid arthritis and inflammatory bowel diseases. Sulfasalazine is an inactive compound (prodrug) that is broken up into its active components sulfapyridine and 5-aminosalicylic acid (5-ASA) by bacterial enzymes in the colon.

Sulfasalazine and its metabolites are believed to have antibacterial properties and also work by suppressing the release of many inflammatory proteins (cytokines). Sulfapyridine is absorbed systemically and is primarily beneficial for rheumatoid arthritis, while 5-ASA has local effects in the colon, useful for inflammatory bowel diseases.

Other DMARDs may be administered as oral tablets or as intravenous (IV) infusions. The uses of other DMARDs include the following:

Hydroxychloroquine sulfate

FDA-approved

• Malaria prevention and treatment
• Rheumatoid arthritis, an autoimmune inflammatory disorder that affects joints
• Chronic discoid and systemic lupus erythematosus, types of autoimmune diseases that affect multiple organs including skin, joints, brain, lungs, kidneys, and blood vessels

Off-label

• Porphyria cutanea tarda, a rare skin condition that caused painful blistering lesions on sun-exposed skin, due to an enzyme deficiency

Leflunomide

FDA-approved

• Rheumatoid arthritis

Rituximab

FDA-approved

• Non-Hodgkin’s lymphoma (NHL) positive for CD-20 (cancer that starts in the lymphatic system and causes abnormal growth of lymphocytes).
• Chronic lymphocytic leukemia (cancer of blood and bone marrow)
• Rheumatoid arthritis
• Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a rare disease that causes inflammation in many tissues including blood vessels
• Microscopic polyangiitis, a condition that causes inflammation in small blood vessels
• Pemphigus Vulgaris, a rare type of autoimmune disease that causes blisters on the skin and mucous membranes

Orphan designation

• Immune thrombocytopenic purpura, a condition with low platelets in the blood that leads to easy bruising and bleeding.
• Rasmussen encephalitis, a rare inflammatory neurological disease

Sulfasalazine

FDA-approved

• Ulcerative colitis, an inflammatory bowel disease
• Rheumatoid arthritis
• Juvenile rheumatoid arthritis

Off-label

• Crohn’s disease, an inflammatory bowel disease

Side effects of other DMARDs vary with each type of drug. A few of the most common side effects include:

• Hydroxychloroquine sulfate:
  • Bone marrow failure and blood disorders
  • Cardiac arrhythmias (irregular heart rhythms)
  • Eye and ear disorders
  • Gastrointestinal and liver function disorders
  • Nervous system and musculoskeletal disorders
  • Psychiatric effects
  • Hypersensitivity reactions
• Leflunomide:
  • Diarrhea and nausea
  • Respiratory infections
  • Alopecia (hair loss)
  • Hypertension (high blood pressure)
  • Rash
  • Bronchitis (inflammation of the bronchial passage)
  • Headache
• Rituximab:
  • Fever, chills, and headache
  • Abdominal pain, nausea, vomiting, and diarrhea
  • Blood disorders
  • Rash and pruritus (itching)
  • Back pain, arthralgia (joint pain), and myalgia (muscle pain)
  • Infection
  • Cough and rhinitis (nasal inflammation)
• Sulfasalazine:
  • Anorexia (loss of appetite)
  • Headache
  • Nausea and vomiting
  • Gastric distress
  • Reversible oligospermia (low sperm count)
  • Urticaria (hives) and pruritus (itching)
  • Anemia (low red blood cell count)

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 some of the other DMARDs include:

• Arava
• Azulfidine
• Azulfidine EN
• hydroxychloroquine sulfate
• leflunomide
• Plaquenil
• Riabni
• Rituxan
• rituximab
• rituximab-abbs
• rituximab-arrx
• rituximab-pvvr
• Ruxience
• sulfasalazine
• Truxima