Systemic Treatments for Psoriasis: Oral and Injectable Options

Psoriasis is a chronic autoimmune condition that leads to inflammation and the rapid turnover of skin cells, resulting in the formation of red, scaly patches. Managing severe cases of psoriasis often requires systemic interventions rather than just topical treatments or phototherapy. 

Systemic treatments, including oral and injectable medications, target the underlying immune dysfunction to provide comprehensive disease control. This article provides an overview of the various systemic treatment options, including their mechanisms of action, benefits, and potential side effects.

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Understanding Systemic Treatments

Systemic treatments are medications that work throughout the body instead of topical treatments or phototherapy, which act locally on the skin. These therapies target the underlying immune dysfunction in psoriasis, providing a more comprehensive approach by suppressing the immune response or correcting abnormal cell turnover.

Systemic treatments are typically prescribed for individuals with moderate to severe psoriasis or psoriatic arthritis, especially when other therapies have not been effective. They are also considered in cases where psoriasis significantly impairs the quality of life and daily functioning or involves large body surface areas.

The primary goals of systemic therapy include reducing inflammation, slowing down the rapid overproduction of skin cells, and managing the symptoms associated with psoriasis. By addressing these key aspects, systemic treatments aim to achieve clearer skin, improve joint symptoms in psoriatic arthritis, and ultimately enhance overall disease control.

Oral Systemic Treatments for Psoriasis

Oral systemic treatments target psoriasis from within the body, offering solutions for moderate to severe cases. Here's a look at key options, their mechanisms, and potential side effects.

1. Methotrexate

• Mechanism of Action: Methotrexate works by inhibiting the enzyme dihydrofolate reductase, which is essential for DNA synthesis and cell replication. This action suppresses the immune system and reduces inflammation, leading to a decrease in psoriasis symptoms.
• Usage: It is commonly used to treat moderate to severe psoriasis and psoriatic arthritis, particularly when patients do not respond to topical treatments alone.
• Benefits: Methotrexate effectively reduces symptoms and improves the appearance of the skin, often leading to significant improvements in disease activity.
• Side Effects: Potential side effects include liver toxicity, nausea, and fatigue, making regular monitoring essential, especially with long-term use.

2. Cyclosporine

• Mechanism of Action: Cyclosporine suppresses the immune system by inhibiting the activation of T-cells, which are involved in the inflammatory process of psoriasis.
• Usage: Due to its rapid symptom-reducing effects, it is typically prescribed for short-term use, particularly during flare-ups of severe psoriasis.
• Benefits: Cyclosporine quickly reduces symptoms, making it especially useful in severe or acute cases.
• Side Effects: Risks include kidney damage and high blood pressure, necessitating careful monitoring during treatment, especially with prolonged use.

3. Acitretin

• Mechanism of Action: Acitretin is a retinoid that helps to normalize skin cell growth and differentiation, making it particularly useful in certain forms of psoriasis.
• Usage: It is often used in pustular or erythrodermic psoriasis cases and can be combined with other therapies for enhanced effectiveness.
• Benefits: Acitretin is effective in specific types of psoriasis, offering a unique mechanism that complements other systemic options.
• Side Effects: Potential side effects include dry skin, hair loss, and teratogenicity, which require careful patient selection and counseling regarding the risks.

4. Apremilast

• Mechanism of Action: Apremilast inhibits the enzyme phosphodiesterase 4 (PDE4), which plays a key role in the inflammatory process. Thus, it reduces inflammation and the severity of psoriasis symptoms.
• Usage: It is indicated for moderate to severe plaque psoriasis and psoriatic arthritis, particularly for those seeking an oral option with a different mechanism of action compared to traditional immunosuppressants.
• Benefits: Apremilast offers a favorable safety profile, making it a valuable option for patients who may not tolerate other systemic treatments well.
• Side Effects: Possible side effects include gastrointestinal issues and mood changes, highlighting the need for ongoing monitoring and patient education during treatment.

Injectable Systemic Treatments for Psoriasis (Biologics)

Injectable biologics target specific immune pathways, offering effective options for managing moderate to severe psoriasis. Here’s a look at key biologics, their uses, and potential side effects.

1. Tumor Necrosis Factor (TNF) Inhibitors

• Examples: Etanercept, Infliximab, Adalimumab.
• Mechanism of Action: TNF inhibitors block the inflammatory cytokine TNF-alpha, which plays akey role in the inflammatory process of psoriasis. By inhibiting TNF-alpha, these biologics help reduce inflammation and slow disease progression.
• Usage: These agents are indicated for moderate to severe psoriasis and psoriatic arthritis, especially in cases where traditional systemic treatments are insufficient.
• Benefits: TNF inhibitors are highly effective in reducing psoriasis symptoms and improving joint health, offering significant relief for those with psoriatic arthritis.
• Side Effects: Potential risks include increased susceptibility to infections, necessitating regular monitoring, and caution in patients with recurrent infections.

2. Interleukin (IL) Inhibitors

• Examples: Ustekinumab (IL-12/23 inhibitor), Secukinumab (IL-17A inhibitor), Ixekizumab (IL-17A inhibitor), Guselkumab (IL-23 inhibitor).
• Mechanism of Action: IL inhibitors target specific interleukins—key signaling molecules in the inflammatory cascade of psoriasis. By blocking these interleukins, IL inhibitors provide targeted control of inflammation and reduce skin lesions.
• Usage: IL inhibitors are typically prescribed for moderate to severe psoriasis, particularly in patients who have not responded adequately to other treatments.
• Benefits: These biologics offer a targeted approach with high efficacy in reducing both skin lesions and systemic inflammation. They provide a focused, therapeutic option with fewer systemic effects compared to broader immunosuppressants.
• Side Effects: Potential side effects include an increased risk of infections and possible long-term impacts on the immune system, highlighting the need for careful patient monitoring.

3. T-Cell Inhibitors

• Example: Alefacept (no longer commonly used).
• Mechanism of Action: T-cell inhibitors reduce the activity of T-cells, which play a central role in the pathogenesis of psoriasis. By targeting these immune cells, T-cell inhibitors help modulate the immune response and control disease activity.
• Usage: Historically, T-cell inhibitors like Alefacept were used to manage psoriasis, but their use has declined in favor of newer, more effective biologics.
• Benefits: These treatments provided a specific approach to targeting immune cells directly involved in psoriasis.
• Side Effects: Safety concerns, such as increased risk of infections and variable efficacy, have led to a shift towards other biologic therapies that offer more consistent results and a better safety profile.

Choosing the Right Systemic Treatment

Selecting the appropriate systemic treatment for psoriasis involves carefully evaluating several factors to tailor the therapy to the patient's needs and circumstances.

Factors Influencing Treatment Choice

• Severity of Psoriasis: Systemic treatments are typically reserved for moderate to severe cases of psoriasis, where the skin surface affected is extensive or when the condition significantly impacts the patient's quality of life.
• Presence of Psoriatic Arthritis: Patients with joint involvement often require systemic treatments that address skin and joint symptoms, such as TNF or interleukin inhibitors.
• Patient Preference: Patient preferences, including the mode of administration (oral vs. injectable), dosing frequency, and potential side effects, play a crucial role in treatment selection. Understanding patient preferences can improve adherence and satisfaction with the treatment.
• Comorbidities: The presence of other health conditions, such as cardiovascular disease, diabetes, or liver issues, may influence the choice of systemic therapy due to potential drug interactions and side effects.

Weighing Benefits Against Risks

Systemic treatments offer significant benefits in managing psoriasis symptoms and improving quality of life, but they also carry potential risks. These treatments often suppress the immune system, increasing the risk of infections and other side effects such as liver or kidney damage. 

It is essential to balance these benefits and risks through a thorough discussion with healthcare providers, considering the patient's health status and treatment goals.

Managing Side Effects and Long-Term Care

Systemic treatments can come with a range of side effects, from mild to severe. Regular monitoring helps identify these early, allowing for prompt management and minimizing the impact on overall treatment success. 

Skipping doses or inconsistent use can reduce the effectiveness of the therapy and may lead to worsening of symptoms. Treatment plans may need adjustments over time based on patient response, side effects development, or disease severity changes. Flexibility in managing these therapies ensures that patients receive the most effective and safe treatment over the long term.

Regular communication with healthcare providers is vital for ongoing care. This partnership helps ensure that any concerns or side effects are promptly addressed and that the treatment plan continues to align with the patient’s needs and health status.

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Key Takeaways

• Systemic treatments target the underlying immune dysfunction in moderate to severe psoriasis, offering more comprehensive control than topical or phototherapy options.
• Oral systemic treatments, such as methotrexate, cyclosporine, acitretin, and apremilast, work by suppressing the immune system, reducing inflammation, and normalizing skin cell turnover. However, they come with potential side effects like liver toxicity, kidney damage, and gastrointestinal issues.
• Injectable biologics, including TNF inhibitors and interleukin inhibitors, provide targeted immune pathway intervention, effectively reducing psoriasis symptoms and inflammation. However, they also carry risks, such as increased susceptibility to infections.
• Selecting the right systemic treatment involves considering the severity of psoriasis, the presence of psoriatic arthritis, patient preferences, and comorbidities, balancing benefits against potential risks.
• Long-term management requires regular monitoring and adjustments to treatment plans to manage side effects and ensure the most effective and safe therapy tailored to the patient’s evolving needs.