Anti-TNF safety: Medical comorbidities present psoriasis treatment challenges

August 1, 2009

As psoriasis patients may have medical comorbidities that would have excluded them from participation in premarketing clinical trials, clinicians must turn to other sources for data to guide therapeutic decisions.

Key Points

Wailea, Hawaii - While the biologics represent a huge advance in the management of moderate-to-severe psoriasis, careful patient selection remains critical. Speaking at MauiDerm '09, experts reviewed treatment considerations for patients with a history of a solid tumor or demyelinating disease.

Although there is a lack of data on biologic treatment and malignancy risk specific to the psoriatic patient population, some guidance on this issue can be sought from analysis of data available from patients with rheumatoid arthritis and psoriatic arthritis, according to Arthur Kavanaugh, M.D., professor of medicine, division of rheumatology, allergy and immunology, University of California, San Diego.

A meta-analysis by Bongartz et al., published in 2006, raised an initial concern that anti-TNF treatment in rheumatoid arthritis patients may be associated with an increased risk of malignancy.

Raising cancer risk?

Overall, data indicate TNF antagonist treatment may perhaps be associated with a small increase in the risk of developing cancer. However, review of the cancers that have developed in TNF antagonist-treated patients shows that they often were detected early after the biologic was initiated, which might suggest any association with treatment may be more due to intensive screening rather than a treatment-induced event, he says.

Analysis of data from registries of patients with rheumatoid arthritis without a history of cancer also do not suggest an increased risk of cancer associated with anti-TNF treatment.

However, results of two randomized, placebo-controlled studies - one a Wegner's granulomatosis trial investigating etanercept (Enbrel, Amgen/Wyeth) and the other a chronic obstructive pulmonary disease (COPD) study of treatment with infliximab (Remicade, Centocor) - suggest that in patients with an inherently elevated risk of cancer from other causes, the biologic treatment might further increase the risk.

Dr. Kavanaugh observes that patients in the COPD study were heavy smokers, and in the Wegner's granulomatosis trial, the patients had received cyclophosphamide; both of these are well-defined risk factors for cancer. The excess cancers that occurred in these studies were of the type that would be expected given these factors.

Registry-based studies have also begun to investigate whether treatment with biologic agents increase the risk of cancer in at-risk populations, specifically persons with a history of cancer.

So far, data have been analyzed from the British Society of Rheumatology Biologics Register that includes information for about 10,000 patients treated with a TNF antagonist and about 2,000 controls who have received disease-modifying antirheumatic drugs (DMARDs) only.

Results

The results showed that after adjusting for other variables, the incidence of cancer was the same or perhaps even lower among patients treated with a TNF antagonist versus those receiving DMARDs. However, there was a suggestion that patients with a past cancer may have an increased risk of developing another malignancy after being started on a biologic.

According to Dr. Kavanagh, it seems reasonable from a theoretical perspective that immunomodulatory treatment may enable earlier onset of a second cancer, although such a phenomenon has not been replicated in all studies.

The conclusions from the registry analysis also need to be interpreted carefully, considering there were very small numbers of patients who developed cancer after starting anti-TNF therapy, as well as the potential for treatment selection bias in patients with a history of cancer.

Findings from a nested case-control study using data from the German Biologic Register found no difference in the incidence of solid malignancies in patients exposed to biologics compared with those on DMARDs, including within the subgroup with a history of cancer.

In addition, preliminary results from analysis of data on survival outcomes from the Swedish Cancer Registry are reassuring in showing there is no major difference in mortality rates between rheumatoid patients treated with a TNF antagonist compared with their unexposed counterparts.

Given the information available about biologic treatment and malignancy risk, when faced with a patient with a prior history of a solid tumor, or even of a nonmelanoma skin cancer, the therapeutic decision-making process should weigh the severity of the psoriasis along with the features of the patient's cancer.