The effectiveness of psoriasis treatments needs to be balanced against the potentially harmful side effects.
Conventional modern medicine prescribes long-term treatment, including systemic therapy (such as methotrexate) and biologic therapies (such as tumor necrosis factor [TNF] ).
Although biologic therapy for psoriasis offers new treatment options with good results and convenience, these medications modify the immune response and change the healthy functioning of the immune system. This exposes patients to potential adverse events.
The risk of serious infection associated with the tumor necrosis factor (TNF) inhibitors is noted in current international guidelines for treating patients with psoriasis, so it is important that we weigh up the effect of treatment on the risk of serious infections.
A six year study of 11 466 patients with psoriasis was carried out from June 2007 through to August 2013 with an overall 8 year observation. Study patients were from North America, Europe, Middle East and Latin America. They were given a variety of psoriasis treatments and were monitored every 6 months during this time, to gauge treatment side effects. The treatments were grouped into Systemic therapy, Biological treatments, Non methotrexate and non biologics treatments.
Systemic therapy treatments
Methotrexate – an immune-modulator, a substance that affects the functioning of the immune system. It works by slowing or stopping the growth of cancer cells and suppressing the immune system. Methotrexate has long been used to treat certain types of cancer or to control severe psoriasis or rheumatoid arthritis.
During the study, 490 patients had received methotrexate (and possibly other nonbiologics). Among these patients, the rates of serious infection were 1.28 per 100 patient-years in the methotrexate cohort.
Biological treatments
Ustekinumab – (Stelara) suppresses the immune system by blocking the inflammatory actions of interleukin (IL)-12 and IL-23, which contribute to the symptoms of psoriasis. Ustekinumab can raise your chances of serious infections, cancer, and a rare condition called reversible posterior leukoencephalopathy, which affects your brain and can be fatal. With the 90 mg dose of ustekinumab, there was one sudden cardiac death in a 33-year-old patient. This was thought to be related to dilated cardiomyopathy. Other events included cellulitis, benign meningioma, transient palpitations and ventricular extrasystoles, and coronary artery disease requiring surgery. There were two serious infections with ustekinumab 90 mg (cellulitis and herpes zoster) and one basal cell carcinoma. Depression was a common adverse event.
Infliximab – a monoclonal antibody which neutralises TNF-alpha in humans. Approximately 16% of patients will have a reaction to infliximab. They may develop urticaria, fevers and chills. Some patients experience falls or rises in blood pressure. Approximately 5% of patients withdrew from clinical trials of infliximab because of adverse events. Other adverse effects include headache, nausea, vomiting and abdominal pain. The patients given infliximab developed more infections than patients given a placebo during trials. Some patients will develop autoantibodies and cases of a lupus-like syndrome have been reported.
Etanercept – (Enbrel) The etanercept molecule is a human tumour necrosis factor receptor fusion protein. It is produced by DNA technology. By inhibiting tumour necrosis factors, etanercept may reduce the body’s defences against infections and tumours. Using etanercept injection may decrease your ability to fight infection and increase the risk that you will get a serious infection, including severe viral, bacterial, or fungal infections that spread throughout the body. These infections may need to be treated in a hospital and may cause death. Tell your doctor if you often get any type of infection or if you think you may have any type of infection now. This includes minor infections (such as open cuts or sores), infections that come and go (such as cold sores) and chronic infections that do not go away. Also tell your doctor if you have or have ever had diabetes, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), or any other condition that affects your immune system.
Adalimumab – (Humira) is in a class of medications called tumor necrosis factor (TNF) inhibitors. It works by blocking the action of TNF, a substance in the body that causes inflammation. Using adalimumab injection may decrease your ability to fight infection and increase the chance that you will develop a serious infection, including severe fungal, bacterial, and viral infection that may spread through the body.
Some children, teenagers, and young adults who received adalimumab injection or similar medications developed severe or life-threatening cancers including lymphoma (cancer that begins in the cells that fight infection). Some teenage and young adult males who took adalimumab or similar medications developed hepatosplenic T-cell lymphoma (HSTCL), a very serious form of cancer that often causes death within a short period of time. Adults who receive adalimumab injection may be more likely to develop skin cancer, lymphoma, and other types of cancer than people who do not receive adalimumab injection.
During the study, 9154 patients had received a biologic agent. Among these patients, the rates of serious infection (measured in patient-years) were:
- 0.83 per 100 patient-years from ustekinumab
- 1.47 per 100 patient-years from etanercept
- 1.97 per 100 patient-years from adalimumab
- 2.49 per 200 patient-years from infliximab
Non methotrexate and non biologics treatments
The systemic therapy combines Acitretin with Psoralen plus UV-A and UV-B.
Acitretin – the efficacy of acitretin is less when used on its own so is used in combination therapy with other systemic psoriasis therapies, especially ultraviolet B or psoralen plus ultraviolet A phototherapy, to increase efficacy. Such combination treatments may potentially minimise toxicity by using lower doses of each of the two agents. All systemic retinoids are potent teratogens which cause malformation of an embryo. Therefore, you must use two acceptable forms of birth control for 1 month before you begin taking acitretin, during your treatment with acitretin, and for 3 years after treatment. Do not donate blood while taking acitretin and for 3 years after treatment. The most common side effects of acitretin are cheilitis and hair loss. Acitretin may cause liver damage.
Psoralen plus UV-A and UV-B – Pigmentation was the most commonly observed side effect seen in 32% of patients using the PUVA treatment, followed by nausea, vomiting, pruritis and headache. Erythema (redness of the skin) was also a commonly observed side effect in patients. Nausea and vomiting was seen in 60% of our patients which is a psoralen related side effect and was seen with equal frequency in PUVA & PUVB groups.
During the study, 1610 patients had received therapy other than methotrexate and biologics. The rates of serious infection among these patients were 1.05 per 100 patient-years in the non-methotrexate and 1.28 per 100 patient-years in the nonbiologics cohort.
About the serious infections
This study evaluates the incidence of serious infections among patients with psoriasis exposed to different biologic therapies in a real-world setting and compares the risk with these individual therapies to the risk with nonbiologic treatments. Based on the standard definition promulgated by the US Food and Drug Administration, a serious infection was defined as any infection that results in death, is life threatening, requires inpatient hospitalisation or prolongs existing hospitalisation, causes persistent or significant disability or incapacitation, or may jeopardise the patient or require intervention to prevent one of these outcomes.
Infections were defined as serious if they were associated with 1 or more of the following:
- death,
- a life-threatening condition,
- persistent or significant disability or incapacitation,
- a cause or prolongation of hospitalization, or
- another medically important condition.
Medically important conditions included infections that may not be immediately life threatening or result in death or hospitalisation but may jeopardise the patient or may require intervention to prevent one of the other conditions included in the definition of serious infections.
The most commonly reported types of serious infections across the study were pneumonia and cellulitis. Increasing age, diabetes mellitus, smoking, significant infection history, infliximab exposure, and adalimumab exposure were each associated with an increased risk of serious infection.
What we found out
Results from 6 year study of 11,466 psoriasis patients who were prescribed psoriasis treatments, the results suggest a higher risk of serious infections with adalimumab and infliximab compared with nonmethotrexate and nonbiologic therapies. No increased risk was observed with ustekinumab or etanercept.
References
Robert E. Kalb, MD1; David F. Fiorentino, MD, PhD2; Mark G. Lebwohl, MD3; et al (2015) Risk of Serious Infection With Biologic and Systemic Treatment of Psoriasis. JAMA Dermatol;151(9):961-969.
