Ritlecitinib - A Pioneering and Approved Drug for Alopecia Areata

Overview:

Ritlecitinib is a medicine used to treat alopecia areata, an autoimmune disorder that causes significant hair loss. It is a member of the class of medications known as Janus kinase (JAK) inhibitors. Ritlecitinib was given the go-ahead by the US Food and Drug Administration (FDA) on June 23, 2023, to treat severe alopecia areata in adults and children 12 years and older. On June 26, 2023, Ritlecitinib received approval in Japan for treating alopecia areata (restricted to intractable cases involving extensive hair loss).

Drug Group:

JAK inhibitors specifically target immune response-related enzymes to treat various inflammatory and autoimmune disorders, including psoriasis (patches of abnormal skin) and rheumatoid arthritis (a severe inflammatory disorder that affects joints). By attaching to the Janus kinases, Jak inhibitors impede this signaling pathway, lowering the generation of inflammatory cytokines and preventing the activation of immune cells.

Dosages:

Adult: This is available in the form of a capsule. Available strength is 50 mg (milligrams).

Pediatric: This is available in the form of a capsule. Available strength is 50 mg (milligrams).

It is indicated for children aged more than twelve years.

For Patients:

What Is Alopecia Areata?

An autoimmune condition called alopecia areata results in hair loss in small, circular patches on the scalp or other body parts. Hair loss results from the immune system erroneously attacking hair follicles. All ages are susceptible, yet the specific reason is unknown. Hair regrowth may occur naturally in some circumstances, although therapies like corticosteroid creams or injections can aid in the process.

What Is the Management of Alopecia Areata?

Topical Treatments:

• Corticosteroids: These are lotions or ointments with anti-inflammatory properties that can be used in the affected areas to lessen swelling and promote hair growth.

• Topical Immunotherapy: This involves injecting substances to the scalp, such as Diphencyprone or Anthralin, to elicit an allergic reaction that may promote hair growth.

Injectable Treatments:

• Intralesional Corticosteroids: Corticosteroids are directly injected into the bald areas to minimize inflammation and encourage hair growth.

Oral Medications:

• Corticosteroids: Oral corticosteroids may be recommended in extreme situations, but they frequently have serious side effects and are not a long-term treatment.

• JAK Inhibitors:A more recent class of drugs called inhibitors can help regulate the immune system while stimulating hair growth. Tofacitinib is one illustration.

Light Therapy:

• Psoralen Plus Ultraviolet A (PUVA) Therapy: This procedure involves applying psoralen to the skin to make it more sensitive to light before subjecting it to UVA light. In some circumstances, this can encourage hair growth.

Supportive Care:

The problem can be managed, and hair health can be promoted with proper hair and scalp care.

If desired, bald spots can be concealed with wigs, hairpieces, or scarves.

Lifestyle and Dietary Changes:

Some people discover that lowering their stress levels and eating a healthy, vitamin and mineral-rich diet can help them feel better.

Monitoring and Follow-Up:

Regular check-ups with a dermatologist are essential to track progress and adjust treatment as needed.

How Does Ritlecitinib Work?

A Janus kinase (JAK) inhibitor called Ritlecitinib treats several inflammatory and autoimmune conditions, including alopecia areata. It explicitly targets JAK enzymes, essential for signal transmission throughout the immune system.

Autoimmune and inflammatory illnesses are characterized by an excessive immune response in which healthy tissues are inappropriately attacked. JAKs play a crucial role in this process by relaying cytokine and growth factor signals, which control the immune response.

JAKs are inhibited by Ritlecitinib, especially JAK1 and JAK3. As a result, it disrupts the signaling pathways that support inflammatory response and immunological activation. The immune response is lowered due to this disturbance, decreasing interleukins and interferon production.

Ultimately, Ritlecitinib aids in regulating the abnormal immune response seen in illnesses like inflammatory bowel disease, psoriasis, alopecia areata, and rheumatoid arthritis. It eases symptoms and stops the spread of disease by lowering inflammation and controlling the immune system. It is important to remember that JAK inhibitors, like Ritlecitinib, might have adverse effects and need close monitoring because they may alter numerous biological functions, including immunological function.

How Should the Drug Be Taken?

The medication is administered orally once a day for people with severe alopecia areata 12 years of age and older. Ritlecitinib's FDA-recommended dose is 50 mg.

Take the missed dose of this medication right away, as they remember. If its time for the next dose, skip the missed one and resume the usual dosing regimen. Not two dosages at once.

Skip the missed dose and resume the regular dosing plan if there are less than eight hours until the next one.

What Are the Benefits of Using Ritlecitinib for Alopecia Areata?

• Immune System Regulation: Ritlecitinib, a Janus kinase (JAK) inhibitor, can assist in controlling the hyperactive immune response found in alopecia areata. It might lessen the immunological onslaught on hair follicles by blocking specific signaling pathways, enabling them to regrow.

• Hair Regrowth: Clinical studies on hair regrowth have produced encouraging results. Some patients had a noticeable increase in hair thickness and density, which can significantly improve their self-esteem and quality of life.

• Convenience: Ritlecitinib is delivered orally, which makes it more convenient for patients to use than other treatments, such as topical corticosteroids or immunosuppressive medications.

• Potential Long-Term Treatment: By treating the underlying autoimmune process, Ritlecitinib may give a more long-lasting treatment for Alopecia areata than some of the current therapies.

What Must the Patient Inform the Doctor Before Taking Ritlecitinib?

• Medical History: Give a thorough account of their medical history, mentioning any current diseases, allergies, or unpleasant drug responses in the past.

• Medications: List all prescription pharmaceuticals, over-the-counter vitamins, and herbal treatments they use because Ritlecitinib may interact with them.

• Breastfeeding: If they are nursing a baby, are pregnant, or plan to become pregnant, then let the doctor know. This could have an impact on whether or not Ritlecitinib will be prescribed.

• Liver or Kidney Problems: Mention any liver or kidney problems, as Ritlecitinib can impact these organs.

• Vaccinations: Discuss the vaccination history with the doctor, especially if an individual has had live vaccines. Ritlecitinib may influence how they react to vaccinations.

• Infections or Illnesses: Report any persistent infections or illnesses since Ritlecitinib may make some infections more likely.

• Alcohol or Substance Use: Ritlecitinib and alcohol or substance use may interact, so let the physician know if they use either.

• Travel Plans: Let the physician know if the patient plans to visit tropical or other areas with a higher risk of contracting an infection.

What Are the Side Effects of Using Ritlecitinib?

• Headache.

• Diarrhea.

• Acne.

• Rash.

• Urticaria (a skin reaction that triggers due to a reaction to the medicine, food, or other irritants).

• Anxiety.

• Black or tarry stools.

• Chest Pain.

• Discomfort.

• Confusion.

• Cough.

• Difficulty breathing.

• Inflamed hair pores.

For Doctors:

Description:

For treating severe alopecia areata (an autoimmune condition that results in patchy hair loss), Ritlecitinib is utilized. This medication affects the immune system by inhibiting Janus kinase 3 (JAK3) and tyrosine kinase.

Each capsule contains the inert substances crospovidone, glyceryl dibehenate, lactose monohydrate, microcrystalline cellulose, and hypromellose (HPMC) capsule shells in addition to 50 mg of Ritlecitinib (equal to 80.13 mg of Ritlecitinib tosylate).

Therapeutic Uses of Ritlecitinib

Ritlecitinib is prescribed for adults and adolescents 12 years and older with severe alopecia areata. It is not advised to combine it with other JAK inhibitors, biological immunomodulators, Cyclosporine, or other potent immunosuppressants.

Dosage Forms and Strengths:

This is available in the form of a capsule. Available strength is 50 mg (milligrams).

Dosage and administration:

As the doctor prescribes, take this medication orally once a day, with or without a meal. Completely consume the capsules. The capsules must not be chewed, split, or crushed.

To reap the greatest benefits from the drug, take it frequently. Take it at the same time every day to aid in memory.

Do not use the medication over the recommended dosage, frequency, or duration. Neither their condition nor their risk of adverse effects will get better faster.

Indications:

Ritlecinib is prescribed for adults and adolescents 12 years of age and older with severe alopecia areata. It is not suggested to combine it with other JAK inhibitors, biological immunomodulators, Cyclosporine, or other potent immunosuppressants.

Contradictions:

• It is contraindicated in patients with severe allergies.

• Malignancies.

• Thromboembolic events.

• Advise patients that vaccination with live vaccines is not recommended during Ritlecitinib treatment.

Precautions:

• The patient's doctor must regularly assess their development. This will enable the physician to assess how well the medication works and determine if it should be continued. To check for unfavorable consequences, blood tests are required.

• Before using this medication, they must have a skin test for TB (tuberculosis).

• Ritlecitinib use may impair the body's capacity to fight infections. Calling a doctor as soon as they notice an infection is crucial.

• The medicine may raise the risk of severe heart or blood vessel problems (such as heart attack or stroke) in people with rheumatoid arthritis who are 50 years of age or older and have a heart or blood vessel condition.

• Ritlecitinib may raise cancer risk (including non-melanoma skin, lung, and lymphoma). Inform the doctor right away, and if the patient experiences any of the following symptoms: black, tarry stools; a general sensation of illness; swollen glands; weight loss; yellow skin and eyes; chronic sores that do not heal; crimson patches or inflamed areas; glossy bumps; pink growths; or white, yellow, or waxy scar-like areas on the skin.

• Do not receive any immunizations (vaccines) without the doctor's permission while the patient is receiving therapy with Ritlecitinib and after they stop taking it. Ritlecitinib may reduce the body's resistance, increasing the risk that the patient will contract the infection that the vaccine is designed to stop.

• Anaphylaxis, a primary allergic reaction that can be life-threatening and necessitate emergency medical intervention, can be brought on by this medication.

What Are the Adverse Reactions of Ritlecitinib?

• Painful or difficult urination.

• Persistent non-healing sore.

• Pink growth.

• Puffiness of the eyelids or around the eyes, face, lips, or tongue.

• A reddish patch or irritated area.

• Shiny bump.

• Slow speech.

• Sore throat.

• Sudden high fever or low-grade fever for months.

• Sweating.

• Swollen glands.

• Weight loss.

• White, yellow, or waxy scar-like area.

• Yellow skin and eyes.

• Hives, itching, skin rash.

• Inability to move the arms, legs, or facial muscles.

• Inability to speak.

• Lower back or side pain.

• Muscle aches.

• Nausea.

• Night sweats.

• Pain, redness, or swelling in the arm or leg.

• Pain or discomfort in the arms, jaw, back, or neck.

What are the Pharmacological aspects of Ritlecitinib?

Mechanism of action:

By inhibiting the adenosine triphosphate (ATP) binding site, Ritlecitinib inhibits Janus kinase 3 (JAK3), and the tyrosine kinase family expressed in hepatocellular carcinoma (TEC) kinases irreversibly.

They may prevent the cytokine signaling and cytolytic activity of T cells implicated in the etiology of alopecia areata. JAK3 and TEC kinase family members are inhibited.

Under normal circumstances, hair follicles are immune-privileged areas with naturally suppressed natural killer cells present. Disruptions to this mechanism, however, can result in alopecia areata and the loss of immunological privilege. Genome-wide association studies have connected the pathophysiology of alopecia areata to the overexpression of UL16-binding protein 3 (ULBP3), a protein that binds to natural killer cell receptors. Hair follicle dystrophy is brought on by the overexpression of ULBP3, which encourages the attack of cytotoxic cluster of differentiation 8-positive (CD8+) NK group 2D-positive (NKG2D+) T cells on hair follicles. Through interferon (IFN) and interleukin-15 (IL-15) signaling pathways, CD8+ NKG2D+ T cells encourage the inflammation of hair follicles, which then activates Janus kinase (JAK)/signal transducer and activator of transcription (STAT) molecular pathways. JAK inhibitors have been suggested as a possible treatment for alopecia areata.

Pharmacodynamics:

Blood cell subsets in patients with alopecia areata, Ritlecitinib therapy was related to a dose-dependent early decrease in absolute lymphocyte counts, T lymphocytes (CD3), and T lymphocyte subsets (CD4 and CD8). Additionally, an early dose-dependent reduction in NK (natural killer) cells (CD16/56) persisted at the lower level through Week 48. Median lymphocyte counts for the 50 mg QD dosage initially decrease. However, this trend persisted until Week 48. No difference in B lymphocytes (CD19) was seen in any therapy group. In the electrophysiology of the heart, there was no clinically relevant effect on the QTc interval at 12 times the mean maximum exposure of the 50 mg once daily dose in alopecia areata patients.

Pharmacokinetics:

The terminal half-life of Ritlecitinib ranges from 1.3 to 2.3 hours. Mostly, it is eliminated by feces and urine. Ritlecitinib, which has been radiolabeled, is eliminated in the urine and feces in roughly 66 percent and 20 percent of cases, respectively. The amount of Ritlecitinib that is unchanged and eliminated in urine is around 4 percent of the dosage. Blood clearance for Ritlecitinib is anticipated to be 5.6 mL/min/kg.

Drug Interactions:

Ritlecitinib interacts with the below-mentioned drugs:

• Abemaciclib.

• Acalabrutinib.

• Adenovirus Vaccine, Live.

• Alfentanil.

• Alosetron.

• Apalutamide.

• Aprepitant.

• Atazanavir.

• Atorvastatin.

• Avanafil.

• Avapritinib.

• Bacillus of Calmette and Guerin Vaccine, Live.

• Bosutinib.

• Brotizolam.

• Budesonide.

• Buspirone.

• Caffeine.

• Carbamazepine.

• Cholera Vaccine, Live.

• Cobimetinib.

• Conivaptan.

• Cyclosporine.

• Daridorexant.

• Darifenacin.

• Darunavir.

• Dasatinib.

• Dengue Tetravalent Vaccine, Live.

• Dihydroergotamine.

• Dofetilide.

• Dronedarone.

• Duloxetine.

• Ebastine.

• Ebola Zaire Vaccine, Live.

• Eletriptan.

• Elvitegravir.

• Entrectinib.

• Enzalutamide.

• Eplerenone.

• Ergotamine.

• Everolimus.

• Felodipine.

• Fentanyl.

• Finerenone.

• Fluticasone.

• Fosaprepitant.

• Fosphenytoin.

• Ibrexafungerp.

• Ibrutinib.

• Indinavir.

• Influenza Virus Vaccine, Live.

• Isavuconazole.

• Ivabradine.

• Ivacaftor.

• Ivosidenib.

• Levomethadyl.

• Lomitapide.

• Lopinavir.

• Lovastatin.

• Lumacaftor.

• Lurasidone.

• Maraviroc.

• Measles Virus Vaccine, Live.

• Melatonin.

• Midazolam.

• Midostaurin.

• Mitotane.

• Mobocertinib.

• Mumps Virus Vaccine, Live.

• Naloxegol.

• Nisoldipine.

• Oxycodone.

• Paritaprevir.

• Phenytoin.

• Pimavanserin.

• Pimozide.

• Poliovirus Vaccine, Live.

• Quetiapine.

• Quinidine.

• Ramelteon.

• Rifampin.

• Rifapentine.

• Rotavirus Vaccine, Live.

• Rubella Virus Vaccine, Live.

• Sildenafil.

• Simvastatin.

• Sirolimus.

• Smallpox Monkeypox Vaccine, Live Non-Replicating.

• Smallpox Vaccine.

• Tacrine.

• Tacrolimus.

• Tasimelteon.

• Temsirolimus.

• Terfenadine.

• Theophylline.

• Ticagrelor.

• Tilidine.

• Tipranavir.

• Tizanidine.

• Tolvaptan.

• Triazolam.

• Typhoid Vaccine, Live.

• Ubrogepant.

• Ulipristal.

• Vardenafil.

• Varicella Virus Vaccine, Live.

• Venetoclax.

• Voclosporin.

• Yellow Fever Vaccine.

• Zoster Vaccine, Live.

Use of Ritlecitinib in specific populations:

• Pregnancy: Regarding use while pregnant, the manufacturer gives no suggestions. There is insufficient data on this drug's use during pregnancy to determine the risk of serious birth abnormalities, miscarriage, or other undesirable maternal or fetal outcomes.

• Lactation: Women should be advised not to breastfeed while receiving therapy with Ritlecitinib and for roughly 14 hours after the last dose (corresponding to approximately 6 elimination half-lives) due to the severe side effects in adults, including risks of serious infection and cancer.

• Pediatrics: Ritlecitinib, an oral once-daily medication for alopecia areata, has been licensed by the FDA for use in children and adults 12 years and older. The FDA has only approved this medication as the first and sole option for adolescent patients with this illness. The safety and efficacy of pediatric patients under 12 have not been investigated.

• Geriatrics: As there is a higher incidence of infections in the elderly population generally, care should be taken when treating the elderly. Age is not the only aspect to consider, although older persons may have different tolerance levels and dangers from medicine. To choose the most appropriate plan option for elderly people, doctors typically examine the individual's general well-being, medical history, and probable adverse effects.