PARIS – with long-term maintenance of disease control and no adverse consequences, Juul van den Reek, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Bruce Jancin/MDedge News
Dr. Juul van den Reek (left) and her coinvestigator and graduate student Selma Atalay
She presented the results of the CONDOR trial, the first-ever formal, randomized, controlled trial of tightly regulated dose reduction of biologics, compared with usual care standard-dose therapy. “Our current advice is we think you can try to reduce the dose because there are a lot of patients who benefit from this,” declared Dr. van den Reek, a dermatologist at Radboud University, Nijmegen, the Netherlands.
The advantages of this strategy are twofold: lower expenditures for this costly collection of medications and less exposure to any long-term, drug-related health risks, she noted.
CONDOR was a Dutch six-center, 12-month, open-label, unblinded, noninferiority, randomized trial including 111 patients. Participants had to have stable low disease activity as defined by both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores of 5 or less for at least 6 months while on standard-dose etanercept (Enbrel), adalimumab (Humira), or ustekinumab (Stelara) prior to enrollment. In fact, the average baseline PASI score was less than 2, with a DLQI of 0.
Participants were randomized to usual care – the customary approved dose of biologic therapy – or a drop down to 67% of that dose, achieved through prolongation of the dosing interval. If the reduced-dose patients kept their PASI and DLQI scores at 5 or less for 3 months straight, they dropped further to 50% of their original dose. However, patients who exceeded those thresholds were immediately returned to their previously effective dose.
The primary endpoint in this noninferiority trial was the difference in mean PASI scores between the dose-reduction and usual-care groups at 12 months. The prespecified margin for noninferiority was a difference of 0.5 PASI points. And that’s where the results get dicey: The mean difference turned out to be 1.1 PASI points in favor of usual care, meaning that, according to the study ground rules, dose reduction was not statistically noninferior. In hindsight, however, that 0.5-point margin was ill-considered and too narrowly defined.
“Within the chosen margins, the dose-reduction strategy seemed inferior. But what is the clinical relevance of a mean difference of 1.1 PASI points, when the accepted minimal clinically important difference is 3.2 points?” Dr. van den Reek observed.
There was no significant between-group difference in DLQI scores at 12 months. Nor did the two study arms differ in terms of the prespecified secondary endpoint of persistent disease flares as defined by a PASI or DLQI greater than 5 for 3 consecutive months: five patients in the reduced-dose group and three in the usual-care arm experienced such flares. There were no serious adverse events or other safety signals related to the intervention.
At 12 months, 50% of patients in the dose-reduction group were well maintained on 50% of their original approved-dose biologic and another 17% were doing well on 67% of their former dose.
Session chair Dedee Murrell, MD, professor of dermatology at the University of New South Wales, Sydney, noted that neither patients nor dermatologists were blinded as to treatment status in CONDOR. She then asked the question on everybody’s minds: Was there any loss of treatment efficacy when patients in the dose-reduction arm needed to resume higher-dose therapy?
No, Dr. van den Reek replied. She added that planned future CONDOR analyses include a cost-effectiveness determination as well as measurement of serum drug levels and identification of antidrug antibodies, information that might prove helpful in identifying an enriched population of patients most likely to respond favorably to biologic dose reduction. In addition, CONDOR-X, a long-term extension study, is ongoing in order to learn how patients on reduced-dose biologics fare after the 12-month mark.
The CONDOR trial was funded by the Netherlands Organization for Health Research and Development; Dr. van den Reek reported having no financial conflicts of interest.