Adalimumab

Adalimumab belongs to the class of biological response modifiers called tumour necrosis factor (TNF) blockers. It is currently approved for the treatment of psoriasis, psoriatic arthritis, rheumatoid arthritis and Crohn disease. In New Zealand, in August 2009, PHARMAC approved funding for severe treatment-resistant psoriasis on Special Authority application.

Adalimumab has the trade name Humira®.

How effective is adalimumab in psoriasis?

Adalimumab has been studied in several thousand adult patients with moderate to severe psoriasis. The efficacy of the medication was judged using PASI (Psoriasis Area and Severity Index) scores before treatment and after using adalimumab 40mg every 2 weeks. More than 70% of patients achieved a 75% reduction in the PASI score at 16 weeks, and in 15-20% the psoriasis cleared up completely.

Adalimumab is not a cure for psoriasis and must be continued long term. Although it continues to be effective in the majority of patients, sometimes the psoriasis recurs despite on-going adalimumab injections.

Adalimumab 40mg every 2 weeks has also been studied in several hundred patients with psoriatic arthritis. Most patients get some improvement in joint pain and swelling in at least a few affected joints and some patients report remarkable benefit from the treatment.

Psoriasis before and 6 months after commencing adalimumab

How does it work?

Adalimumab is a recombinant monoclonal antibody containing only human peptides. It works by directly binding to TNF molecules in the blood and diseased tissue. TNF bound to adalimumab is prevented from causing the inflammation that results in psoriasis plaques.

How is it given?

Adalimumab is administered by subcutaneous injection once every two weeks. It is available as a pre-prepared syringe or pen. After initial counselling and training, patients can usually self-inject into the thigh or abdomen. A different site should be used at each injection to reduce soreness and prevent the skin from becoming tender, red, bruised or hard.

Adalimumab treatment

Removing the caps from the pen

Giving the subcutaneous injection

Pressing on the injection site

The recommended dose for treating psoriasis is 80mg then 40 mg a week later, followed by 40mg every fortnight as a single dose.

Other medications including methotrexate and acitretin can usually be continued during treatment with adalimumab.

Pretreatment tests

Dermatologists are likely to request routine blood count, liver and renal function, fasting lipids and antinuclear antibody before starting adalimumab. In females, a pregnancy test may be appropriate.

Patients should be tested for tuberculosis (TB) and active or latent viral hepatitis. If present, these infections should be treated before starting adalimumab.

Precautions

Because adalimumab works by selectively targeting TNF, theoretically it should not have much effect on the rest of the body's immune system. However, caution must be taken when considering its use in patients prone to infections or in those with chronic or recurrent infections. It is wise to avoid concurrent treatment with ciclosporin as the combination increases the risk of infection.

Uncommon infections with organisms such as listeria and legionella may be more common and more serious in patients on adalimumab.

As they may induce illness in immunodeficient individuals, live vaccines should not be used during treatment with adalimumab. Currently available live attenuated viral vaccines include measles, mumps, rubella, varicella, yellow fever, influenza (intranasal vaccine) and oral polio vaccine. Live attenuated bacterial vaccines include BCG and oral typhoid vaccine.

Adalimumab should also be used with caution in the following situations:

• Congestive heart failure: it should not be used by patients with moderate or severe heart failure
• Pre-existing or recent-onset CNS demyelinating disorders (e.g., multiple sclerosis)
• Patients with skin cancer or at high risk of skin cancer

Patients on anakinra, a drug used in rheumatoid arthritis, should not be prescribed adalimumab.

The safety of adalimumab during pregnancy and breastfeeding is unknown. It is therefore not recommended. Where possible, the drug should be discontinued several months before conception.

Adverse effects

Adalimumab appears to be well tolerated. Mild to moderate injection site reactions (redness, swelling, itching, pain) appear to be the most common side effect, occurring in 20% of patients. Mild to serious infections are the main risk of treatment and should be promptly treated.

Severe cutaneous reactions have rarely been reported, including worsening psoriasis, vasculitis, anaphylaxis, Stevens Johnson syndrome and toxic epidermal necrolysis.

Like all medications that work on the immune system, it may increase the risk of certain types of lymphoma (white blood cell cancer). These have rarely been reported in patients on adalimumab, usually in those also taking other medicines that suppress the immune system such as azathioprine or mercaptopurine.

Skin cancers, in particular squamous cell carcinoma, have also been reported in patients on adalimumab, usually in patients with other risk factors such as previous treatment with photochemotherapy (PUVA).

A full list of reported adverse effects is described in the manufacturer's datasheet for Humira.