Therapeutic strategies

Key points:

• Rotational treatments aim to prevent toxic doses accumulating in the patient's body and to overcome the problem of a treatment becoming less effective over time.
• Sequential treatments involve higher doses of medications being prescribed for a short time and then gradually replaced or combined with other drugs.
• In both strategies, there is a risk that the patient will cling to a drug, despite its toxicity.
• Combined therapies bring together several drugs in order to optimise their effectiveness.

Monotherapy refers to psoriasis treatment with a single agent. Advantages of this approach include convenience and simplicity. The primary disadvantage is the occurrence of unwanted side effects that occurs with prolonged use of many agents.

To overcome the limitations of monotherapy, many dermatologists use combination therapy in which 2 or more agents with different mechanisms of action are used together. This approach has been proven to maximize the clinical benefits and tolerability of each agent while simultaneously limiting their side effects. The most commonly used combination regimen pairs as a superpotent corticosteroid with a vitamin D analogue (Calcipotriol).

Rotational therapy involves utilizing a single agent for a specific period of time and then switching to another agent(s). This involves stopping an effective, but potentially toxic therapy and initiating treatment with less dangerous, but possibly less effective, treatment.

Rotational therapy is more commonly used in the treatment of more severe disease where the use of potentially toxic systemic agents such as methotrexate, cyclosporine or oral retinoids is required.

The objective is to avoid a cumulative dose that would be toxic for the patient (a number of drugs have side effects). It can also be used to overcome the problem of a treatment becoming less effective over time, as is frequently the case for a monotherapy.

For example, for severe cases cyclosporine may be prescribed at first, followed by a retinoid six months later and subsequently another drug. Similarly, when a patient has a flare of psoriasis or has side effects resulting from one drug, the doctor can prescribe a different monotherapy.

Topical medications can also be used in rotation. This therapeutic strategy is used mainly in moderate to severe psoriasis, and can be followed with or without scheduled interruptions in treatment.

The doctor may prescribe a rotational treatment from the beginning or as a result of the patient's clinical response. 

Sometimes it is more effective to prescribe high doses of one drug for a short period and then combine it with other drugs. The ideal doses then needed to be calculated in order to achieve optimal results with minimal toxicity. One of the sequences used involves administering cyclosporine at high doses for a month, and then combining it with a retinoid for two months. When the second drug starts to have an effect, the doctor decreases the dosage of the first. This sequence is repeated for each new flare. 

As regards rotational therapy, there are disadvantages. For example, it is impossible to predict how the patient will react to the new drug. Moreover, there are no standardised alternating treatments as every patient responds differently to treatment. It all depends on the patient's history, age, severity of lesions and course of the condition. For both strategies, there is a risk that patients will cling to an effective treatment, even if it is toxic. Both doctor and patient must consent to whatever therapy is chosen.

The term "combination therapy" is used when several treatments (local or systemic) are used at once. For example, for more severe cases a dermatologist may prescribe phototherapy and retinoids. Such combinations are used when the treatments act in synergy and results are more rapid.

A topical therapy combining two compounds (a vitamin D analogue and a corticosteroid) is also available, providing a fast acting, effective and well tolerated treatment option. Irritant effects of vitamin D are reduced by the corticosteroid.

Combined therapies do not necessarily multiply side effects as dermatologists have knowledge and experience on which medications that combine well.

However, certain drugs, such as immunosuppressants, must not be combined, and every drug has a maximum dosage which should not be exceeded.