Ixekizumab - Indications, Pharmacology, Warnings, and Precautions

Overview

Ixekizumab is a routinely prescribed medication that possesses wider therapeutic applications. It is proven to be highly potent against psoriatic arthritis, which is a peculiar form of arthritis having a close association with a skin condition called psoriasis. The United States Food and Drug Administration (FDA), a drug regulatory authority, endorsed Ixekizumab’s therapeutic usage for tackling psoriatic arthritis in December 2017. It is endorsed for both single-drug therapy and combination therapy. Currently, it is widely marketed under various brand names with specific indications.

Drug Group:

Ixekizumab falls under the monoclonal antibody drug class. Ixekizumab is categorized as an interleukin inhibitor under the monoclonal antibody class. As the name suggests, monoclonal antibodies are laboratory-made protein molecules that structurally resemble human proteins (antibodies). These genetically engineered drug molecules are designed in such a way that they exhibit interaction with only specific targets.

Available Doses and Dosage Forms:

Ixekizumab is marketed in liquid form and intended for injecting into the fatty layer underneath the skin. 80 milligrams per milliliter is the available dosage strength of the injection solution. The doctor determines the individual dosage, and accordingly, the required quantity of the injection solution is administered. The injection formulation is available in prefilled syringes and autoinjectors for single-dose administration.

For Patients

What Is Psoriatic Arthritis?

Psoriatic arthritis, as the name suggests, is a unique ailment where a joint issue (arthritis) co-exists with a skin condition (psoriasis). Psoriasis is an immune-mediated skin problem where the person experiences itching, redness, and skin peeling, which develop due to an exaggerated immune response in the skin cells. However, certain patients may develop the condition even without pre-existing psoriasis. Studies suggest that psoriatic patients are more susceptible to developing psoriatic arthritis in the long run. There is still confusion concerning the underlying causative factors that could evoke psoriatic arthritis. It shares the manifestations of both arthritis and psoriasis. However, the psoriatic signs are restricted to the palms and fingernails, where pitting, scaling, and reddened rashes develop in and around the fingernails. The person may experience soreness, puffiness, and deformation in the joints. The affected joints tend to vary with the form of psoriatic arthritis. Monoclonal antibody therapy is considered an effective therapeutic intervention for alleviating the manifestations and discomfort associated with psoriatic arthritis.

How Does Ixekizumab Work?

Ixekizumab deals with the manifestations of psoriatic arthritis through its interleukin-17A (IL-17A) inhibitory mechanism. Interleukin-17A is a specific protein molecule that has the potential to influence how immune cells respond. It potentially augments the immune response against inflammatory conditions, thus contributing to its exacerbation. Since abnormal and atypical immune responses mediate psoriatic arthritis, Ixekizumab can effectively tackle the immune response by checking the activity of interleukin-17A, thereby alleviating the manifestations associated with psoriatic arthritis. As the Ixekizumab drug molecule is structurally designed to target the interleukin-17A molecule specifically, all the autoimmune conditions that IL-17A influences can have beneficial therapeutic effects with this drug.

What Is the Dosage of Ixekizumab?

160 milligrams (mg) is the advised loading dose of Ixekizumab at week zero for psoriatic arthritis. Following this, the maintenance dose of 80 mg is advised once every four weeks. If the patient has co-existing psoriasis, appropriate modifications in the drug dosages are made accordingly. Sometimes, Ixekizumab is advised in conjunction with other medicines as part of combination therapy. In such cases, necessary dosage adjustments must ensure optimum effectivity within the safer limits.

How Effective Is Ixekizumab?

Ixekizumab effectively deals with the inflammatory changes associated with psoriatic arthritis. Remarkably, it brings down the pace of disease progression. Its therapeutic potency and safety aspects were proven in clinical trials. Ixekizumab holds an enhanced safety profile when matched with other drugs that are generally advised for psoriatic arthritis. Further deterioration of the joint structure by psoriatic arthritis can be potentially geared down with Ixekizumab therapy. By alleviating the discomfort and other clinical manifestations associated with psoriatic arthritis, Ixekizumab offers a better quality of life for patients suffering from psoriatic arthritis.

What Are the Things to Inform the Doctor Before Taking the Drug?

The treating doctor should better understand the patient’s medical background. Sharing vital information with the doctor is imperative to ensure the success of the treatment.

• Patients who have had prior allergic encounters with Ixekizumab need to inform their doctors before commencing the therapy. Individuals who elicited exaggerated reactivity to other monoclonal antibody drugs should also keep the doctor aware of it. Such patients are more susceptible to eliciting an exaggerated immune response to Ixekizumab.

• A detailed drug history is another important thing that the doctor should be informed of. The drug history should be elaborate and comprehensive, encompassing all the medications that a person takes, is planning to take, or has taken long back. All sorts of medications, irrespective of herbal, over-the-counter, dietary supplements, or alternative medicines, should be disclosed. Drug history enables doctors to assess the risk for potential drug-to-drug association, which would otherwise bring about unwanted effects in the body.

• The doctor should be informed of the patient’s medical history. Underlying ailments, past medical conditions, surgeries undergone, or planning to undertake everything should be informed before initiating the therapy using Ixekizumab.

• Inform the doctor if the patient is due for any vaccine. Patients should refrain from getting live vaccines while undergoing therapy using Ixekizumab. Therefore, discuss the vaccination status with the doctor and ensure it is current.

• The doctor should know the patient’s pregnancy and lactation status. Any form of pharmacological intervention during pregnancy and lactation bears risk and possibility for unpredictable complications. If an unexpected conception occurs, before proceeding with the therapy course, discuss it with the concerned doctor and seek medical advice.

How Is Ixekizumab Administered?

Ixekizumab is marketed in a liquid formulation meant for administration through injections. The medicine has to be deposited into the fatty layer underneath the skin (subcutaneous) with the help of a syringe and needle. Medical supervision is advised for the drug delivery through subcutaneous injection. However, the patient or their caregivers can be trained on the subcutaneous injection technique, which eliminates the need for periodic hospital visits for drug administration.

Ixekizumab medicine formulation is marketed in prefilled syringes and autoinjectors, enabling patients to deliver the injection shot themselves. The thigh, abdomen, and upper arm are suitable sites for subcutaneous delivery of Ixekizumab. Alternating the injection site gives time for the skin reactions that develop at the injection point to settle down. The injection formulation of Ixekizumab should be brought to room temperature before being delivered subcutaneously. Once it is cooled, look for abnormalities like precipitate, cloudiness, or discoloration, and if found, the injection formulation should be disposed of.

What Are the Side Effects of Ixekizumab?

Like any other medicine, Ixekizumab does possess certain side effects. Some of the routinely reported side effects of Ixekizumab include the following:

• Injection point soreness, diarrhea, weight loss, nausea, and abdominal pain.

• Eye discomfort includes frequent tearing, flaming, and itching sensations.

• Stuffy nose and troubled breathing.

• Chest discomfort and facial puffiness.

• Skin rashes are present in the form of hives.

• Dizziness and collapse.

Dietary Considerations:

No specific dietary regulation needs to be followed for Ixekizumab therapy. If there are no specific dietary guidelines, the patients should follow a balanced diet as it is critical to enhance one's health.

Missed Dose:

Sometimes, the patient fails to deliver the dose at the stipulated time and becomes aware of the later overlooked dose. If the subsequent dose is at the door, passing over the missed one is strictly advised. No attempt should be made to alter the dosage to compensate for the overlooked dose.

Overdose:

Administering more than the prescribed amount of Ixekizumab injection formulation can bring about overdose issues. Overdosing may remarkably exaggerate the side effects and result in harmful health hazards. Trouble breathing, abnormal body movements (seizures), and fainting are alarming signs of potential overdosing, which mandates immediate medical attention. The poison control center needs to be contacted upon acute overdosing.

Storage:

Ixekizumab’s storage temperature range is ideal at two to eight degrees Celsius (36 to 46 degrees Fahrenheit). However, the Ixekizumab injection formulation remains safe for therapeutic application under room temperature (36 degrees Celsius) for five days. Since there are no added preservatives in the injection formulation, exposure to room temperature for over five days may deteriorate the therapeutic properties, making it unsafe for administration. Though the medicine is advised to be refrigerated, care should be taken not to let the liquid formulation freeze. Refrigerate the medicine along with its packaging.

For Doctors

Indications:

• Psoriatic arthritis (adult patients).

• Plaque psoriasis (patients over six years to elderly adults).

• Ankylosing spondylitis (adult patients).

• Non-radiographic axial spondyloarthritis (adult patients).

Dose:

1. Psoriatic Arthritis: The dosage regimen for patients detected with psoriatic arthritis in the active stage consists of loading and maintenance doses. Loading dose corresponds to the initial dose given at week zero, while all the subsequent doses are considered maintenance doses.

• Loading Dose: 160 milligrams (mg) is the preferred loading dose of Ixekizumab. It is delivered into the body through two subcutaneous injections, each contributing 80 milligrams of Ixekizumab. Loading dose is injected at week zero.

• Maintenance Dose: 80 mg is the maintenance dose administered at an interval of four weeks.

2. Ankylosing Spondylitis: The dosage regimen for ankylosing spondylitis is the same as that of psoriatic arthritis.

3. Plaque Psoriasis: The dosage regimen for plaque psoriasis differs for adult and pediatric patients. In the case of adult patients, the Ixekizumab therapy commences (week zero) with a loading dose of 160 milligrams. Following this, a maintenance dose of half the loading dose is delivered on alternate weeks until the 12th week. After the 12th week, the frequency of maintenance dose is titrated down to once every four weeks. For child patients (over six years), their body weight must be taken as a guiding factor for dose determination.

4. Non-radiographic Axial Spondyloarthritis: Patients detected with non-radiographic axial spondyloarthritis are advised 80 mg of Ixekizumab. Subsequent doses need to be spaced by a four-week gap.

Dosing Considerations:

Before initiating the therapy with Ixekizumab, it is imperative to ensure that the corresponding individual is not due for any vaccination. Vaccination status should be up to date with the immunization guidelines. No other specific dosing considerations are advised for Ixekizumab therapy for psoriatic arthritis.

What Are the Pharmacological Aspects of Ixekizumab?

• Mechanism of Action: Being a monoclonal antibody, Ixekizumab is structured so that it could hinder the activity of the cytokine interleukin 17A. Ixekizumab interacts with these cytokine molecules and establishes a bond with them. This prevents interleukin 17A from eliciting its pro-inflammatory actions responsible for psoriatic arthritis exacerbation. Pro-inflammatory properties of interleukin favor the inflammation process and augment its intensity. Ixekizumab, being a potent interleukin 17A inhibitor, hinders the interaction of interleukin 17A with their corresponding receptors. In this way, Ixekizumab blocks the inflammatory mediators and dampens the interleukin 17A-mediated immunological responses.

• Pharmacodynamics: There is not much reliable information concerning the pharmacodynamic aspects of Ixekizumab. Pro-inflammatory chemokines and cytokines get impeded by Ixekizumab’s immunosuppressive properties.

• Pharmacokinetics: Ixekizumab’s utmost concentration following drug introduction is accomplished after four days. Ixekizumab’s bioavailability was reported to be higher following subcutaneous delivery in the thigh region than in other preferred areas. Once the therapy reaches its eighth week, the Ixekizumab’s blood concentration remains steady. Under steady-state conditions, it exhibits a 7.11 L (liters) volume of distribution. As a humanized protein-based drug molecule, Ixekizumab does not possess any metabolic pathways, unlike conventional drugs. However, like human antibodies, these monoclonal antibodies will be chymified into simpler amino acids by proteolysis.

Toxicity:

There is no conclusive evidence concerning the toxicity potentialities associated with Ixekizumab.The absence of relevant clinical study reports makes it challenging to comment on the toxicity potentialities. The literature reports are also ambiguous, with certain reports pointing to Ixekizumab’s carcinogenic potentials while others reported no association with carcinogenic properties. Further studies and assessments are needed to establish and demonstrate Ixekizumab’s carcinogenic, tumorigenic, and mutagenic potentialities. As per the nonclinical study reports, Ixekizumab does not influence fertility.

Clinical Studies:

Placebo-controlled, double-blinded, randomized clinical trials were conducted on 679 subjects in the adult age range to demonstrate the safety and potency aspects of Ixekizumab. Only those patients who failed to precipitate desirable results or exhibited intolerance with conventional therapies for active psoriatic arthritis were chosen as subjects for the clinical trial. Study results illustrated enhanced therapeutic effects and treatment outcomes in subjects trialed with Ixekizumab compared to those who were trialed with either a placebo or other standard drugs like Adalimumab.

What Are the Contraindications of Ixekizumab?

Individuals who have had prior allergic encounters with Ixekizumab should refrain from Ixekizumab therapy as it is considered to be a potential contraindication. Hypersensitivity response to any of the components listed among the ingredients of Ixekizumab also carries the potential for an anaphylactic reaction following subsequent exposure. Hence, such individuals are not supposed to undertake Ixekizumab therapy.

Warnings and Precautions:

• Vaccinations: It is imperative to ensure that the patient is updated with the vaccination status. If there is any vaccine that is due for administration, it should be taken before commencing Ixekizumab therapy. Patients who have undergone Ixekizumab therapy should refrain from getting live vaccines.

• Susceptibility to Infections: Ixekizumab therapy works by depreciating the body’s immune response. It remarkably dampens the immune status, encouraging microbial invasion and making one vulnerable to infections. Conjunctivitis, respiratory infections, tinea infections, and candidiasis are frequently ported in patients undergoing Ixekizumab therapy. Therefore, immediate medical advice must be sought in case of a suspected infection.

• Inflammatory Bowel Disease: Ixekizumab therapy potentiates the possibility of inflammatory bowel disease. Therefore, the patients who are undergoing Ixekizumab therapy need to be periodically reviewed for signs of inflammatory bowel disease.

• Rule Out Tuberculosis: Patients with active tuberculosis infection should not undergo therapy using Ixekizumab. Anti-tuberculosis drugs need to be advised in patients who had prior encounters with tuberculosis infection. In addition, all patients chosen for Ixekizumab therapy should undergo screening to confirm the absence of tuberculosis.

• Hypersensitivity: Ixekizumab also poses the risk of exaggerated reactivity. Sudden onset facial puffiness, labored breathing, and skin rashes are indications of hypersensitivity reactions. Hypersensitivity reaction mandates immediate withdrawal of Ixekizumab and hospital admission.

What Are the Drug Interactions of Ixekizumab?

Ixekizumab is often administered in conjunction with other drugs. Therefore, it is essential to understand how Ixekizumab interacts when simultaneously administered with other medications. However, no remarkable interaction is observed when Ixekizumab is simultaneously administered with Methotrexate, Sulfasalazine, Warfarin, Midazolam, or other nonsteroidal anti-inflammatory drugs (NSAIDs).

Specific Considerations:

• Ixekizumab During Pregnancy: Because of limited study reports, there is no conclusive evidence suggesting the detrimental effect of Ixekizumab on pregnant women. However, there are possibilities for fetal harm. Being an immunoglobulin, Ixekizumab may be able to breach the placental barrier, thus gaining access to the fetus. Drug exposure in the uterine stage can bring in abnormalities like birth defects in the fetus. Therefore, potential risks and clinical needs for the maternal body must be weighed before advising Ixekizumab for pregnant women.

• Ixekizumab During Lactation: No relevant information is available concerning the discharge of Ixekizumab through breast milk following administration to a lactating mother. Considering the risk of unwanted exposure to Ixekizumab in the baby’s body, these are generally not advised for lactating women. However, the doctors evaluate the therapeutic benefits and risks concerning Ixekizumab and advise accordingly.

• Ixekizumab in the Pediatric Population: Studies have established the safety and therapeutic efficacy aspects of Ixekizumab in pediatric patients over six years of age. However, its pediatric usage is limited to children under six years old as its therapeutic properties must be explored more before advising them.

• Ixekizumab in the Geriatric Population: Ixekizumab’s therapeutic potentialities in the geriatric population were analogous to those of adults.