Biologics for Psoriasis (TNF, IL-23, IL-39, IL-17, and CD-6 Inhibitors)

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biologics for psoriasis

Biologics for Psoriasis are used in patients who have moderate to severe disease or are not responsive to conventional therapies. Biologics for psoriasis are both effective and tolerable. They have good short-term and long-term efficacy.

The most common side effect associated with the use of biologics for psoriasis is the increased incidence of infections. TNF-alpha inhibitors can activate latent infections like tuberculosis. Patients with rheumatoid arthritis treated with infliximab and etanercept have seen an increase in infection rates. Patients who receive biologic therapy with methotrexate may also be at higher risk of developing herpes zoster. There has been a slight increase in candidal infections due to anti-IL-17 biologic drugs, such as brodalumab and secukinumab.

Similarly, adult patients with psoriasis who received infliximab or adalimumab had a greater risk of serious infections compared to patients treated with non-biologic (conventional DMARDs).

Biologics For Psoriasis Include:


Biologics for Psoriasis – TNF-alpha inhibitors:

The biologic tumor necrosis factor-alpha (TNF-alpha) inhibitors used for psoriasis are etanercept and infliximab.

  • Etanercept (Enbrel) for the treatment of Psoriasis:

    • Etanercept has been FDA-approved for adults with psoriasis and patients aged four years and older who have severe to moderate plaque psoriasis. Adults receive a subcutaneous injection of 50mg twice weekly during the first three months, and then a 50mg injection once weekly as maintenance therapy. The standard pediatric dose is 0.8 mg/kg per week, with a maximum of 50 mg each week. Psoriatic arthritis can also be treated with Etanercept.
    • Etanercept (Enbrel) treatment has been found to improve psoriasis and psoriasis associated with fatigue and depression.
    • Etanercept-szzs is a biosimilar to etanercept that’s safe and effective in moderate to severe plaque psoriasis patients.
    • Anti-etanercept antibody formation has been reported in 0-18% of patients who have received the drug for psoriasis. The formation of anti-etanercept antibodies does not seem to decrease treatment efficacy, contrary to the presence of antibodies against infliximab or adalimumab among patients with psoriasis.

Enbrel is used to treat Psoriasis and Psoriatic Arthritis

  • Infliximab (Remicade) for Psoriasis:

    • TNF-alpha inhibitor, infliximab is beneficial for patients with moderate to severe plaque psoriasis. It appears to be well tolerated and has a rapid onset of action compared to most other biologic agents. Adults should receive an intravenous infusion at 5 mg/kg for weeks 0, 2, 6, and 8, followed by eight weekly infusions thereafter. Treatment with infliximab is also effective in patients with psoriatic arthritis.
    • The efficacy of infliximab in patients with moderate to severe psoriasis has been evaluated in multiple studies. It has also been observed that higher doses may result in prolonged treatment response. However, compared to placebo medicines, the risk of serious infections and other adverse drug reactions including malignancies is higher with infliximab.
    • In the RESTORE 1 Trial, Infliximab was found superior to methotrexate in patients suffering from moderate to severe psoriasis.
    • Research in psoriasis and inflammatory bowel diseases, as well as rheumatoid, suggests that some patients may lose their response to infliximab due to the production of antibodies. Infliximab-treated psoriasis patients are affected by anti-infliximab antibodies in between 5 and 44 percent.
    • Infliximab -dyyb is a biosimilar drug to infliximab. A randomized study that included patients with infliximab responsive diseases including psoriasis showed that switching to infliximab -dyyb was no less effective than continuing originator infliximab treatment.

Infliximab rapidly improves symptoms of psoriasis

  • Adalimumab (Humira) for the treatment of Psoriasis:

    • Adalimumab is a humanized monoclonal antibody that has activity against TNF alpha. It was initially used to treat rheumatoid and is now effective in treating psoriasis as well. The FDA approved Adalimumab for adult patients with severe to moderate chronic plaque psoriasis. Adults are advised to receive an 80 mg subcutaneous injection followed by 40 mg every other week. This is the standard dosing schedule for adalimumab.
    • Adalimumab has been found to be superior to placebo and methotrexate in patients with moderate to severe psoriasis. It may be used as an alternative treatment in patients who have an inadequate response to Etanercept (Enbrel).
    • The formation of antibodies against adalimumab has been reported in 6 to 50% of patients receiving adalimumab treatment for psoriasis. This may decrease the effectiveness of therapy.

Adalimumab (Humira) is effective in Etanercept resistant psoriasis

  • Certolizumab pegol for the treatment of Psoriasis:

    • Certolizumab pegol is an antibody Fab fragment that can be pegylated and humanized with specificity for TNF alpha. The FDA approved the drug in 2018 for adults with moderate to severe cases of psoriasis. The standard dosing schedule for certolizumab includes 400 mg once a week. Patients weighing less than 90 kg can opt for 400 mg in weeks 0, 2, 4, and 4. Then, 200 mg is given every other week.
    • Certolizumab pegol has a potential advantage in that it does not transfer to the placenta like other anti-TNF biologics. This is because unlike other anti-TNF biologics certolizumab pegol lacks the IgG Fc. It is also very effective in treating other autoimmune diseases apart from its role in the treatment of psoriasis.
    • Certolizumab was found to be superior to placebo in the treatment of moderate to severe psoriasis. In higher doses (400 mg administered every two weeks), Certolizumab was also more effective than Etanercept. However, at lower doses, Etanercept and Certolizumab were equally effective in clinical trials.

Unlike other Biologics for psoriasis, certolizumab does not cross the placental barrier


IL-17 Pathway Inhibitors in the Treatment of Moderate to Severe Psoriasis:

The interleukin 17 pathway inhibitors used for the treatment of psoriasis are secukinumab and ixekizumab.

  • Secukinumab for the treatment of Psoriasis:

    • Secukinumab is an anti-IL-17A monoclonal anti-inflammatory antibody that can be used to treat moderate to severe plaque psoriasis. Plaque psoriasis treatment is standard 300 mg subcutaneously given once a week at weeks 0, 2, 3, and 4, followed by 300 mg every other four weeks. For some patients, 150 mg is sufficient. Secukinumab can also be used to treat psoriatic arthritis.
    • Secukinumab is more effective than placebo and Etanercept in the treatment of moderate to severe psoriasis. It is more effective for moderate to severe plaque-related psoriasis than ustekinumab, and in treating psoriasis compared to guselkumab and risankizumab.

Secukinumab may be more effective than Etanercept

  • Ixekizumab for the treatment of psoriasis:

    • The FDA approved Ixekizumab in March 2016.  It is indicated for the treatment of mild to severe plaque psoriasis in adults. Standard dosing of Ixekizumab includes 160 mg in week 0, 80 mg in weeks 2, 4, 6, 8, 10, and 12. Then, 80 mg is given every four weeks. Ixekizumab can also be used to treat psoriatic arthritis.
    • Ixekizumab has been found to be superior to placebo and etanercept in the treatment of patients with moderate to severe plaque psoriasis. It is well tolerated and has a comparable safety profile. Furthermore, it induces faster disease recovery and remissions.

Among the biologics for psoriasis, Ixekizumab induces faster recovery

  • Brodalumab for the Treatment of Psoriasis:

    • Brodalumab is an anti-IL-17 receptor monoclonal antibody that has high efficacy in treating psoriasis. Brodalumab was approved by the FDA for treatment of mild to severe plaque psoriasis. It can be used in adults who have not responded to or lost response to systemic therapy or phototherapy. Dosage recommendations are 210 mg every other week. The United States will require that patients who are being treated with the drug must participate in a Risk Evaluation and Mitigation Strategy program. This is due to the potential for suicide attempts and complete suicides.

Among the biologics for psoriasis, brodalumab is associated with suicidal risks

    • Brodalumab has been found to be effective in the treatment of plaque psoriasis. Compared to Patients who received ustekinumab, Brodalumab treatment was associated with a higher rate of complete skin clearance.

Bradlumab treatment is associated with a higher rate of complete skin clearance


IL-23 Inhibitor Therapy in the treatment of Psoriasis:

Antipsoriatic drugs that have anti-interleukin 23 activity include Ustekinumab, Guselkumab, Tildrakizumab, And Risankizumab.

  • Ustekinumab for the treatment of Psoriasis:

    • Ustekinumab is a monoclonal human antibody that targets IL-12/IL-23. Ustekinumab can be used to treat adults and children aged 12 and over with moderate or severe psoriasis. It is also suitable for those who are candidates for systemic therapy or phototherapy.
    • Ustekinumab dosage is based on weight. Adults weighing less than 100 kg should be given 45 mg at weeks 0, 4, and 12 thereafter. Adults over 100 kg should receive a 90 mg dose in the same manner. It is also effective in the treatment of psoriatic arthritis.
    • The efficacy of the drug has been proven in various clinical trials. It is a highly effective form of therapy for the treatment of patients with psoriasis. The drug’s efficacy persists beyond three years. It has minimal side effects and can be tolerated by most patients.
    • It has also been found to be effective in those patients who did not respond to Etanercept treatment. It can be used as monotherapy or methotrexate.
    • There are concerns regarding the association of IL-23/IL-12 inhibitors with adverse cardiovascular events that need to be confirmed in large trials and meta-analyses.
    • There may be anti-ustekinumab antibodies in as many as 4 to 6 percent of patients who have received ustekinumab treatment for psoriasis. However, it is not known if there has been any effect on the treatment efficacy of the anti-ustekinumab-producing antibody.

The CVS safety of Ustekinumab is yet to be confirmed

  • Guselkumab for the Treatment of Psoriasis:

    • Guselkumab is a monoclonal antibody to human immunoglobulin G1 lambda monoclonal antibody that binds the p19 subunit in IL-23. This p19 subunit is also found in IL-39. Psoriasis’ mechanism of action is thought to be inhibition of IL23 signaling.
    • Guselkumab should be taken at 100 mg for weeks 0, 4, and 8. It is also being studied in patients with psoriatic arthritis. The efficacy of the drug has been proven in patients with moderate to severe plaque psoriasis. Guselkumab was even more effective than adalimumab.
    • In patients with plaque psoriasis who had an inadequate response to ustekinumab, Guselkumab treatment was more effective. Similarly, it was found to be more effective than secukinumab over the long term.
    • In comparison with Ixekizumab, it was observed that patients who received Ixekizumab had a more rapid clinical response.
    • Guselkumab is known to cause upper respiratory tract infections, herpes simplex virus infection, tinea, gastroenteritis, arthralgia, and other symptoms.

Ixekizumab induces a rapid clinical response

  • Tildrakizumab for the treatment of psoriasis:

    • Tildrakizumab is a monoclonal human immunoglobulin G1 kappa monoclonal anti-human immunoglobulin G1 antibody (IgG1) that binds the p19 subunit IL-23. The FDA approved Tildrakizumab in 2018 for adults with mild to severe plaque psoriasis. The recommended dosing schedule is 100 mg subcutaneously every week between weeks 0 to 4, and then every 12 months.
    • It has greater efficacy in severe plaque psoriasis compared to placebo and etanercept.
  • Risankizumab for the treatment of psoriasis:

    • Risankizumab is a humanized monoclonal antibody is directed against the p19 subunits of IL-23 & IL-39. 2019 FDA approval for Risankizumab was granted to adults with moderate to severe plaque psoriasis who are eligible for phototherapy or systemic therapy. The recommended dose for Risankizumab in adults is 150 mg per week 0 through week 4, and then every 12 weeks.
    • Risankizumab has been found to be more effective than placebo and ustekinumab. It was also found to be more effective than adalimumab in plaque psoriasis with comparable adverse drug reactions.

CD-6 antibody directed therapy in Psoriasis:

  • Itolizumab:

    • It is a monoclonal anti-T cell costimulator CD6 antibody that can be used to treat psoriasis. Itolizumab does not exist in the United States.
    • Itolizumab is superior to placebo in the treatment of plaque psoriasis moderate to severe.
    • The phase III trial’s response rates were lower than those of ustekinumab and adalimumab in phase III trials. Itolizumab’s efficacy has not been directly measured against other biologic agents.

Summary:

The novel biologic drugs that are used to treat patients with severe psoriasis primarily target the TNF pathways, the T-cell stimulation pathways, and the Interleukin Pathways.