NEW YORK (Reuters Health) – Patients who would have been ineligible for clinical trials of psoriasis treatments are more likely to suffer serious side effects from these treatments compared to patients who could have participated in the trials, researchers from Spain have found.
“I think that we should be aware of the uncertainties about systemic psoriasis therapy in the large group of patients ineligible for randomized clinical trials,” Dr. Ignacio Garcia-Doval from Complexo Hospitalario de Pontevedra told Reuters Health in an email. “We are less sure about the efficiency or safety of these drugs in up to 30% of the patients receiving them, such as elderly patients, those with psoriasis forms different from chronic plaque psoriasis, or those with previous cancer or chronic infections. In some of these groups the risk-benefit ratio might be very different from the one described in clinical trials.”
Dr. Garcia-Doval and colleagues used data from the Spanish Registry of Adverse Events Associated With Biologic Drugs in Dermatology (BIOBADADERM) to investigate the proportion of patients receiving systemic drugs for psoriasis in clinical practice who were not adequately represented in randomized controlled trials (RCTs) and whether these patients have a different risk of serious adverse events.
Overall, 29.8% of the patients would have been excluded from RCTs, most commonly due to psoriasis other than chronic plaque psoriasis (12.2% of patients), age older than 70 years (7.4%), chronic liver disease (5.9%), or a history of hepatitis B infection (4.5%).
The overall rate of serious adverse events was substantially higher among patients not eligible for RCTs (41.6 vs 16.5 per 1000 person-years), the authors reported this month in Archives of Dermatology.
Among all patients, serious adverse event rates were higher with biologics than with classic systemic drugs (27 vs 14.4 per 1000 patient-years).
Out of the 1,042 patients in the registry, 59 developed serious adverse events (29 of the 732 patients who would have been eligible for an RCT, and 30 of the 310 patients who would have been excluded). Most patients (35/59, 59.3%) recovered without sequelae, 12 (20.3%) had not yet recovered at the time of data collection, nine (15.3%) had recovered with sequelae, and three (5.1%) had died (none of causes related to the drugs).
In multivariable analyses, factors significantly associated with an increased risk of serious adverse events included ineligibility for RCTs (a 2.6-fold increase), exposure to biologics (a 2.3-fold increase), age over 70 years (a 3.4-fold increase), and history of cancer (a 4.8-fold increase).
“Patients ineligible for most randomized clinical trials are more likely to suffer from adverse events during systemic therapy for psoriasis (although not necessarily caused by therapy),” Dr. Garcia-Doval concluded. “They require a careful prescribing, with individual evaluation of the risk-benefit balance, and a more intensive monitoring.”
“There is a need for research in generalizability of randomized clinical trials and on how to apply results from these studies to individual patients,” Dr. Garcia-Doval added.
Arch Dermatol 2012;148:463-470.