Research in context
Evidence before this study
Pemphigus is a life-threatening autoimmune blistering disease affecting the skin and mucosa. The combination of high doses of systemic corticosteroids and conventional immunosuppressive drugs, mostly azathioprine and mycophenolate mofetil, is regarded as standard treatment for severe cases of pemphigus. However, only 50% of patients achieve complete remission off-therapy. Many patients relapse and require a maintenance corticosteroid therapy, leading to high cumulative doses of corticosteroids and accompanying side effects. We searched PubMed for articles published from 2002–2015 with the terms “pemphigus” and “rituximab”. We identified more than 400 patients with severe types of pemphigus refractory to conventional immunosuppressive drugs, who were treated with rituximab as second-line or third-line treatment. A few studies compared the first-line use of adjuvant immunosuppressive drugs as steroid-sparing agents versus placebo. Unfortunately, none of the findings from these studies showed a clear beneficial effect from the addition of conventional immunosuppressants to corticosteroids alone. High rates of short-term complete remission between 70% and 80% were reported with good tolerance, but with a 30%–60% relapse rate. Given this high efficacy of rituximab in the refractory type of pemphigus, results from a few case reports have suggested that its use as first-line treatment in pemphigus might permit rapid tapering of corticosteroid doses. Because long-term corticosteroid treatment is responsible for severe and even life-threatening side-effects in patients with pemphigus, we did a randomised trial comparing treatment with a high dose of prednisone alone given for 12 to 18 months with a regimen of rituximab plus lower initial doses of prednisone, rapidly tapered over 3 to 6 months. Our aim was to assess whether first-line rituximab plus short-term prednisone could substantially improve the occurrence of long-term complete remission off-therapy in patients with pemphigus, while allowing a decrease in cumulative doses of prednisone and a reduction of severe treatment adverse events, compared with prednisone alone.
Added value of this study
This is the first trial of patients with pemphigus that compared a regimen of high doses of corticosteroids alone with a regimen of rituximab plus low dose of corticosteroids. The findings showed that first-line use of rituximab with short-term prednisone resulted in an increase in achievement of complete remission off-therapy at month 24 of almost three times compared with a corticosteroid-alone regimen. Additionally, median cumulative duration of complete remission-off-therapy was more than seven times higher in patients assigned to rituximab plus short-term prednisone. Patients in the rituximab plus short-term prednisone group also took about one-third of the prednisone cumulative dose that the corticosteroid-alone group took, and had about half as many severe adverse events.
Implications of all the available evidence
Data from our trial suggest that a regimen of rituximab plus low dose corticosteroids could be used as first-line treatment in patients with moderate to severe pemphigus. The regimen is highly effective, allows rapid tapering of corticosteroids, and causes fewer treatment adverse events than a regimen using corticosteroid doses alone.