Complement inhibitor drugs are medications designed to manage certain immune responses. They specifically target a part of the body’s natural defense system to prevent it from causing harm. Their primary purpose is to address situations where this immune component becomes overly active, leading to damage to healthy tissues.
The Complement System
The complement system is a complex network of proteins circulating in the blood, forming a part of the innate immune system. Its normal role involves identifying and eliminating foreign invaders like bacteria and viruses. This system also helps clear dead cells and immune complexes from the body, maintaining overall health. It acts as a cascade, where one protein activates the next, ultimately leading to the removal of threats.
When functioning properly, the complement system is a beneficial defense mechanism. However, if dysregulated or overactive, it can mistakenly target and damage the body’s own healthy cells and tissues. This uncontrolled activation can lead to inflammation, cell destruction, and organ damage, contributing to various autoimmune and inflammatory diseases.
How Complement Inhibitor Drugs Work
Complement inhibitor drugs function by blocking specific proteins or pathways within the complement cascade. These medications prevent uncontrolled activation that can harm healthy tissues. For instance, some inhibitors bind directly to complement proteins like C5, preventing its cleavage into active components. This action halts the downstream steps of the cascade, including the formation of the membrane attack complex, which is responsible for cell lysis.
Other inhibitors target different points in the cascade, such as C3 or Factor B, aiming to reduce overall complement activity. By selectively interfering with these components, the drugs reduce inflammation and prevent damage to healthy cells. This targeted approach helps modulate the immune response without completely shutting down the entire complement system, which would leave the body vulnerable to infections.
Diseases Treated by Complement Inhibitor Drugs
Complement inhibitor drugs are prescribed for several rare diseases where an overactive complement system contributes to the disease’s progression. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder where red blood cells are destroyed by uncontrolled complement activity. Medications like eculizumab and ravulizumab target the C5 protein, preventing the lysis of red blood cells in PNH patients. These drugs significantly reduce the need for blood transfusions and improve patient outcomes.
Atypical hemolytic uremic syndrome (aHUS) is another severe condition involving uncontrolled complement activation, leading to kidney failure and damage to other organs. Eculizumab is also used in aHUS to inhibit C5, thereby preventing the formation of blood clots and protecting organ function. Generalized myasthenia gravis (gMG), an autoimmune neuromuscular disorder, can also involve complement-mediated damage at the neuromuscular junction. Ravulizumab and zilucoplan are C5 inhibitors used to treat gMG, reducing muscle weakness.
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease affecting the optic nerves and spinal cord, where complement activation contributes to neurological damage. Ravulizumab is approved for NMOSD to reduce disease flares and progression. Pegcetacoplan, which targets C3, is used for PNH and is being investigated for other complement-mediated conditions like C3 glomerulopathy (C3G). C3G is a rare kidney disease characterized by abnormal C3 protein deposits, leading to kidney damage. Crovalimab, another C5 inhibitor, is also being developed for PNH, while pozelimab is under investigation for other complement-mediated conditions.
Administration and Potential Side Effects
Complement inhibitor drugs are typically administered through intravenous infusion or subcutaneous injection. Intravenous infusions, like those for eculizumab, are given in a clinical setting, often every two to four weeks. Subcutaneous injections, such as with pegcetacoplan, allow for more frequent, self-administration at home, usually daily or every other day. The specific route and frequency depend on the drug and the condition being treated.
While these drugs are effective, they carry potential side effects. A significant concern is an increased susceptibility to serious infections, particularly meningococcal infections, because the complement system plays a role in fighting these bacteria. Patients receiving these treatments are therefore strongly advised to be vaccinated against meningococcal disease before starting therapy. Other common side effects may include headaches, nausea, or fatigue, and patients are monitored regularly for any adverse reactions during treatment.