Maintenance with rituximab monotherapy prevents relapse in severe pemphigus
By Marilynn Larkin
NEW YORK (Reuters Health) – Rituximab can be administered alone, without systemic corticosteroids, to prevent relapse in patients with severe pemphigus, researchers in France say.
“Pemphigus is a rare, chronic, relapsing, and potentially life-threatening autoimmune bullous dermatosis,” state Dr. Philippe Bernard of Reims University Hospital and colleagues. “European guidelines recommend administration of systemic corticosteroids as a first-line therapy.”
To assess whether rituximab could be used instead of steroids to maintain remission, the team conducted a single-center, retrospective case-series study of adults with a confirmed diagnosis of pemphigus vulgaris or foliaceus. All had been treated with at least one cycle of rituximab for steroid dependence, resistance or adverse events.
Of 27 patients who received at least one cycle of rituximab, 11 (median age, 42; five women) received additional cycles of the drug as maintenance therapy without any other treatment.
Maintenance monotherapy consisted of a single rituximab infusion (1 g) given every six months, in some cases decreasing after 18 months to once yearly. The median duration of treatment was 33 months, and the median number of infusions was six.
As reported in JAMA Dermatology, online January 3, all 11 patients remained in complete remission during maintenance therapy, with no adverse events.
However, five of the 11 experienced grade 3 or 4 adverse events between the initial cycle and the first rituximab maintenance infusion: one had sepsis; one had hypertension; and two each had diabetes or endocrine disorders.
The 11 patients were in complete remission at last follow-up (median, 78 months after the first rituximab cycle), with 10 having discontinued rituximab.
“The results of this case series indicated that rituximab can be used as single maintenance therapy, without a systemic corticosteroid, with good efficacy and tolerance in patients having severe pemphigus requiring long-term therapy for prevention,” the authors conclude.
Dr. Adam Friedman, Director of Translational Research and of the Supportive Oncodermatology Clinic at George Washington School of Medicine and Health Sciences in Washington, DC, commented, “Pemphigus vulgaris is fortunately a rare but sadly chronic, life-altering and even life-threatening autoimmune blistering disease for which we have few effective treatments. While high-dose steroids is the treatment of choice, it certainly cannot be maintained due to numerous health risks, nor is it always effective.”
“The age of biologic therapies . . . has changed the landscape for the treatment of inflammatory skin diseases and even skin cancer,” he explained in an email to Reuters Health. “Rituximab . . . is not approved for pemphigus but is well known for its efficacy in treating this disabling disease.”
“I applaud these investigators for taking the creative initiative to evaluate long-term maintenance,” he said. “We always have to think about the long game even once the condition is under control.”
“The difficulty in translating these findings will be getting insurances on board, as this is a super-expensive treatment and given the lack of U.S. Food and Drug Administration approval, coverage is often rejected.”
“It is disappointing that in this age, insurance dictates a patient's treatment, not the physician,” he observed. “We must, however, push on and continue to encourage studies such as these to reveal potential treatment algorithms that can be effective and safe long-term.”
Dr. George Murakawa, a dermatologist at Beaumont Hospital in Royal Oak, Michigan, told Reuters Health, “Rituximab has been shown in this study and others to be an effective treatment option for these patients.”
“Because orphan diseases are not seen on a frequent basis, pharmaceutical company-based studies for ‘on-label’ usage are not usually conducted, thus leaving these patients with extremely few treatment options,” he said by email. “Moreover, when these medications are used off-label, the government considers this fraud and treatment is not covered.”
“Few options are available for the most difficult-to-treat diseases,” Dr. Murakawa concluded.
Dr. Bernard did not respond to requests for comment.
JAMA Dermatol 2018.(c) Copyright Thomson Reuters 2018. Click For Restrictions - http://about.reuters.com/fulllegal.asp