Rheumatology Journal Club #2: Rituximab for AAV Relapse
In its second Twitter-based discussion, the online rheumatology journal club RheumJC pondered a study that shows rituximab effective for relapse in ANCA-associated vasculitis. The 387 "tweets" are reduced here to 11 easy-to-read slides.
In its second Twitter-based discussion, the new online rheumatology journal club, RheumJC (hashtag #rheumjc2) considered a followup to the landmark RAVE study that showed rituximab (RTX) noninferior to cyclophosphamide (CYC) for ANCA-associated vasculitis (AAV).What happens when patients relapse? The small extension study featured in this discussion found rituximab again effective, regardless of the initial treatment. Should the information in this 26-patient followup inspire a change of practice?Round 2 of RheumJC took place in two sessions (3 PM and 9 PM EST) on March 3. Here, in 11 slides, you see the high points of the discussion compiled and organized for easy reading, with citations (and hyperlinks) in the slide captions.The 46 participants at this second round included rheumatologists from severalSee also:Rheumatology Journal Club Debut: The Twitter Conversation Condensed.states,16 nations outside the US, and-a promising precedent-the lead author of the study itself (as well as one enterprising high school student).Immediate access to participants worldwide has led to Twitter "being used in innovative ways in medicine never imagined by the original developers," wrote one of RheumJC's founders, Minnesota-based rheumatologist Paul Sufka MD, in a blog published shortly after this second #RheumJC discussion.He named 3 advantages to holding a journal club on Twitter: increased number of participants, broader range of knowledge and experiences, and ability to interact directly with authors of the study in question. Â
The second round of the Twitter-based RheumJC featured a discussion of a followup to the RAVE study testing rituximab for relapses after treatment of ANCA-associated vasculitis. The following 11 slides follow the discussion in order.
In the RAVE study, rituximab (RTX) proved noninferior to cyclophosphamide (CYC) for induction therapy of AAV. A small followup trial showed RTX also effective for patients who ultimately relapse, regardless of their prior treatment. The latter is the topic of this discussion.
1. Miloslavsky EM, Specks U, Merkel PA et al.Rituximab for the Treatment of Relapses in Antineutrophil Cytoplasmic AntibodyâAssociated VasculitisArthritis & Rheumatology, 2014; 66: 3151â3159. doi: 10.1002/art.38788
2. Stone JH, Merkel PA, Spiera R et al.N Engl J Med. 2010;363(3):221-32. doi: 10.1056/NEJMoa0909905
Question 1: What induction treatments for AAV do specialists prefer today? Among these rheumatologists, RTX is the favored choice, but nephrologists are less familiar with it than with CYC -- although they would prefer an alternative. CYC is still the standard for very sick patients, and seems to act faster than RTX.
For those using CYC for induction, is the chosen course of therapy 3 months or 6? The latter, two rheumatologists agree, or remission -- whichever comes first. Another favors continuing for the full 6 months.
An aside: Why did they choose that dose of RTX for the RAVE study? It differs from the standard dose used for rheumatoid arthritis.
Another question about the original RAVE trial leads to a long discussion: What is the optimal period for steroid tapering in AAV patients, given the trade-offs between the risks of infection and relapse? The tapering schedule used in the RAVE trial seemed unusually fast. The author of the followup study, present for the discussion, reveals a new pilot study underway that may help to answer the question.
... and another brief aside, this one about the comparative kinetics of cell depletion for CYC and RTX in ANCA-associated vasculitis. Again, the author of the followup study provided an answer in the first session. (Others repeated it for those who attended the later session.)
Is it better to schedule treatment for AAV pre-emptively or wait for relapse to start RTX? Participants differ. Not for the first time in this session, the troublesome issue of insurance reimbursement rears its head.
Guillevin L, Pagnoux C, Karras A, , Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis.N Engl J Med 2014;371(19):1771-80. doi: 10.1056/NEJMoa1404231
What's the best practice for monitoring biomarkers (B cells or ANCA) to watch for relapse in patients with AAV? Again, practices differ. But the question prompts an interesting suggestion from a nephrologist (and the second of 3 "re-tweetworthy" observations).
Stegeman CA, Tervaert JWC, deJong PE et al,TrimethoprimâSulfamethoxazole (Co-Trimoxazole) for the Prevention of Relapses of Wegener's GranulomatosisN Engl J Med 1996; 335:16-20 doi:10.1056/NEJM199607043350103
What are the limitations of this followup study? Participants list 4 major problems, but one says that the original RAVE study was so sound we should pay attention nonetheless.
The takeaway: Will this change how you treat your patients with relapsing AAV? It already has, says one participant. The question is whether third-party payers will go along with this use for rituximab (which prompts the third "re-tweetworthy" quote).
