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Long-term safety – part 2/2

tuberculosis, but, according to several registry data, they are also linked with an increased rate of other opportunistic infections, especially those with intracellular micro-organisms. A meta-analysis of registry data and long-term extension studies, restricted to rheumatoid arthritis, concluded that there was no documented increased risk of total malignancy and NMSC associated with anti-TNF therapy.37

increased in 3–5% of patients treated with infliximab.15

Real-world data from registries and record linkage analyses A medical registry can be defined as a ‘systematic collection of information on all the cases of a particular disease or other health relevant conditions.’ In parallel with the advent of biologics, several treatment registries have been implemented in different clinical areas. Registries of psoriasis patients treated systemically are active at a local, regional, national or international level. A collaboration among some of these registries is ongoing, in the so-called Psonet collaboration.33

At this stage, only

limited data are being delivered by psoriasis registries, as data collection and follow-up are still limited. Within the Spanish BIOBADADERM study, 632 patients receiving biologics and 417 patients receiving conventional systemic therapy were compared for the period from October 2008 to November 2009,

alongside retrospective data on patients treated with biologics since 2005.34 Suspension of biologic therapy due to AEs was rare (72 cycles, 10%). A total of 232 AEs were reported in patients receiving biologics versus 43 in patients on conventional treatment. The most frequent AEs were infections in patients treated by biologics, and metabolic or nutritional abnormalities in patients on conventional treatment. The relative risk of infections or infestations in patients receiving biologic drugs was 23 (p< 0.01). Most of the registry data available up to now concern indications different from psoriasis, namely, several

rheumatological diseases. These data point to an increased risk of tuberculosis in anti-TNF-treated patients and consistently show that the risk is much higher in patients treated with monoclonal antibodies, that is, infliximab and adalimumab, compared with those treated by the fusion protein etanercept.35,36

Not only do monoclonal antibodies increase the risk of

As previously highlighted in part 1 of this chapter, the international PSOLAR registry is ongoing, focusing on the safety of systemic treatments (including ustekinumab) in psoriasis, supported by the manufacturer. The registry is expected to enrol and follow up over time a total of 12,000 patients, with 4000 patients treated by ustekinumab. With the increasing role of electronically based information management, record linkage that involves combination of data from different electronic databases would allow the quick testing of the hypotheses concerning safety. One example is offered by a recent US study combining data from Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid, and national Medicaid/Medicare programs. The incidence of herpes zoster was compared, adjusted by propensity score, between new TNF antagonists users (n=33,324) and patients initiating nonbiologic disease-modifying antirheumatic drugs (DMARDs) (n=25,742).38

For patients with rheumatoid

arthritis, adjusted incidence rates were similar between anti-TNF and nonbiologic DMARD initiators and comparable between all three anti-TNF therapies studied. Similarly, patients with other inflammatory diseases, initiated on anti-TNF therapies, were not at higher risk of herpes zoster compared with patients who initiated nonbiologic treatment regimens.

How should the safety profile of biologics influence choice of therapy?

While regional guidelines for the treatment of psoriasis are different, treatment guidelines in a number of countries recommend the use of TNF antagonists or IL-12/23 inhibitors as the first-line biologic therapy for patients who are unresponsive to, or intolerant of, non-biologic systemic agents.39,40

Based on

registry data, etanercept may be associated with a lower risk of tuberculosis 25

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