Background/Purpose: Two independent controlled randomized trials recently reported the efficacy and safety of rituximab (RTX) monotherapy in severe cryoglobulinemic vasculitis (CV) (1, 2), with one reporting a follow-up lasting two years (1). The aim of this study is to report the very long term efficacy and safety of a retreatment regimen with RTX administered at clinical relapse after the end of the abovementioned trial (1).

Methods: Long term follow up data of a trial of RTX in severe CV (1) were analysed, by considering patients managed with retreatent with RTX at clinical relapse. During this follow-up, only RTX monotherapy was used. Number of retreatments, disease activity at last follow up, adverse events and causes of deaths were registered. Clinical response was evaluated at the last follow-up visit, as follows: i) complete response (remission), partial response (response > 50% of at least one manifestation among glomerulonephritis, severe neuropathy or skin ulcers) (1), and active disease despite treatment.

Results: After the end of the 24-month controlled trial (1), follow-up data were analysed in 30 patients, all positive for hepatitis C virus infection. The mean follow up after the beginning of RTX therapy (1) was 72.6±20.4 months, including 24 (80%) patients followed for more than 4 years and 6 (20%) patients followed for 2.4-4 years. Of them, 21 patients were still under an active follow up, 3 patients were lost from follow-up shortly after the end of the trial, and 6 patients died. Survival of RTX regimen was 7.6±0.3 yrs (mean±standard error). Seventeen out of 30 (56.7%) patients needed a retreatment for relapse; of them, 6/30 were retreated during the trial, 10/30 only after the end of the trial and 1/30 during both follow-up periods, accounting for 25 retreatments in total, the first one at a mean of  22.3 ± 12.1 months from last RTX cycle during the trial. Patients were retreated for nephritis (7/25), neuropathy (12/25), skin ulcers (6/25) or widespread purpura (6/25). Of the 17 patients retreated, 6/17 (35.3%) showed complete response at the last follow-up, 5/17 (29.4%) a partial response, while 6/17 (35.3%) had an active disease. Interestingly, of the remaining 13/30 patients undergoing only one single course of RTX during the follow-up, 6/13 were still in active follow-up and in clinical remission at the last follow-up. Recurrent infections occurred in three patients (10%; urinary and upper respiratory), related to severe hypogammaglobulinemia (IgG < 3 g/l) in 2/3. Death occurred in 6 patients. However, only 2/6 deaths were linked to relapsed vasculitis, with new onset of intestinal vasculitis.

Conclusion: A long-term RTX monotherapy with a retreatment at relapse regimen is effective and safe in cryoglobulinemic vasculitis, with low rate of severe hypogammaglobulinemia. Clinicians should be aware to promptly recognize and treat clinical relapse, as well as concomitant infections. Relapses with life-threatening manifestations (i.e. intestinal vasculitis) were uncommon. Further investigation may be required to select patients where maintenance RTX therapy may be the best choice.

References:

1) De Vita S, et al. Arthritis Rheumatol. 2012;64(3):843-53.

2) Sneller MC, et al. Arthritis Rheumatol. 2012;64(3):835-42.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-rituximab-retreatment-regimen-at-clinical-relapse-in-severe-cryoglobulinemic-vasculitis/