Now a randomized follow-up trial in adults from two previous studies (SOLO 1 and SOLO 2) reports that maintenance monotherapy with dupilumab (Dupixent, Regeneron) at 300 mg weekly or biweekly over 36 weeks is the most consistently effective monotherapy regimen for eczema control in those who responded to the biologic previously.
Administration every 4 or 8 weeks showed a dose-dependent reduction in response with no safety advantage.
“This study supports the use of 300 mg of dupilumab weekly or every 2 weeks as effective regimens in adults with moderate to severe AD for long-term maintenance of treatment response,” the authors conclude.
Margitta Worm, MD, PhD, a professor and senior physician in the Department of Dermatology, Venerology and Allergology at Charité-Universitätsmedizin Berlin in Germany, and colleagues published their findings online December 26 in JAMA Dermatology.
SOLO-CONTINUE Trial Studied Maintenance in Dupilumab Responders
The Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (SOLO-CONTINUE) trial found that more frequent dosing schedules resulted in a negligible change in percentage Eczema Area and Severity Index (EASI-75) improvement from the previous SOLO 1 and SOLO 2 trials (–0.06%; P < .001 vs placebo).
The percentage change with less frequent regimens worsened in a dose-dependent manner: every 4 weeks, –3.84%; every 8 weeks, –6.84%; placebo, –21.67%.
Despite the typical waxing and waning of eczema symptoms, more patients treated at weekly or biweekly intervals (76.1%) maintained EASI-75 response than those on 4- (58.3%) or 8-week (54.9%) schedules, or on placebo (30.4%).
SOLO-CONTINUE is a 36-week, randomized, double-blind, placebo-controlled phase 3 trial of 422 patients who were successfully treated with dupilumab 300 mg in SOLO 1 and SOLO 2. The study was conducted at 185 sites in North America, Europe, Asia, and Japan.
Participants in the current cohort had a mean age of 38.2 years and 53.8% were male. As previous responders, they had achieved Investigator’s Global Assessment (IGA) scores of 0 or 1 or a 75% or higher improvement in the EASI-75 score at week 16 in SOLO 1 and SOLO 2, which used 300 mg at dosing intervals of 1 and 2 weeks.
Current patients were randomly assigned in 2:1:1 ratio to the two dosing schedules of the previous trials, to less frequent regimens, or to placebo for an additional 36 weeks. For all study endpoints, those on the original dosage of 300 mg weekly (n = 89) or every 2 weeks (n = 80) achieved better maintenance than those with less frequent dosing every 4 weeks (n = 86) or every 8 weeks (n = 84). Maintenance was significantly better than placebo (n = 83).
In addition, a less frequent treatment schedule, particularly every 8 weeks, was associated with a higher risk for skin infections, flares, and rescue medication use than the standard treatment schedule.
Adverse event incidence was 70.7% for weekly or biweekly dosing, 73.6% for dosing every 4 weeks, 75% for dosing every 8 weeks, and 81.7% for placebo. Rates of conjunctivitis were comparable in all groups.
Interestingly, treatment-emergent antidrug antibody incidence was higher with less frequent administration or placebo: 11.3% for placebo and, respectively, 11.7%, 6%, 4.3%, and 1.2% for administration every 8 weeks, every 4 weeks, every 2 weeks, and every week. These findings suggest that less frequent administration results in higher immunogenicity, the authors write.
They caution that their results may not apply to the broader AD population because the trial sample was confined to previous strictly defined responders to the study drug.
In an accompanying editorial, Peter A. Lio, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, notes that disease severity and quality-of-life measures have significantly improved recently, and these “have raised the bar for AD treatment, mirroring the more stringent treatment goals that have been defined for patients with psoriasis.”
Although perhaps not as exciting as investigations of a new agent, Lio says this type of longer-term maintenance study is invaluable to practitioners prescribing dupilumab to their patients. “As more patients are exposed to the drug, more will want or need to reduce the dosage or stop use over time,” he writes. “Although it seems most optimal to continue an every-2-week treatment regimen, this simply may not always be feasible. Better understanding of the options and implications around decreasing the dosage is helpful as we integrate new therapies and learn more about AD.”
Dupilumab, the first biologic for AD, is “literally a life-changing drug for many patients with extensive, moderate-to-severe disease. With its targeted, highly specific suppression of the chemical messengers IL 4 and IL 13, it’s like a miracle,” Theodore Rosen, MD, a professor of dermatology at Baylor College of Medicine in Houston, Texas, told Medscape Medical News. Rosen was not involved in the study.
Rosen said the current results help answer questions to which answers have been lacking. “Often, we have a successful treatment with a drug for a chronic disease but then we ask, now what? We don’t know when or how or if we should stop the drug.”
The clear message from these results is that patients are much more likely to stay clear if they are maintained on a long-term weekly or every-other-week regimen at no more than the standard 300 mg dose, Rosen explained.
Although the biologic is costly, Rosen said the cost is offset by patients’ increased quality of life and productivity and less usage of the healthcare system and other medications.
Offering another perspective on the findings, Bruce A. Brod, MD, said the study supports the current recommended dosing regimen of every 2 weeks as opposed to less frequent intervals. Brod is a clinical professor of dermatology at the University of Pennsylvania Perelman School of Medicine in Philadelphia.
Regarding the future, he told Medscape Medical News, “The dosing schedule needs to be evaluated in patients with a partial response since the study group only included patients who were high responders.” In addition, he said, it might have been helpful to look at a dosing schedule of every 3 weeks.
Dupilumab was recently approved for the treatment of moderate to severe AD in children aged 12 to 17 years.
This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc.
Worm reports receiving honoraria for consulting and lecture activity from Regeneron Pharmaceuticals, Inc and Sanofi during the conduct of the study and outside the submitted work. She also reports personal fees from Regeneron, Sanofi, ALK-Abello, Allergopharma GmbH & Co, Allergy Therapeutics Plc, HAL Allergy B.V., LEO Pharma, Mylan Germany GmbH, and Novartis outside the submitted work. Numerous study coauthors report financial relationships with multiple private-sector companies, including Regeneron and Sanofi; others report employment by or stock ownership in private companies. A complete list is available on the journal’s website.
Lio reports financial ties to Regeneron and Sanofi Genzyme as well as financial ties, including stock options, to other companies. Rosen and Brod have disclosed no relevant financial relationships.