From the Director
![DUKE.RESEARCH.NIGHT.03 (1)](http://news.medicine.duke.edu/wp-content/uploads/2013/06/DUKE.RESEARCH.NIGHT_.03-11-277x300.jpg)
What Did I Read This Week?
Submitted by: David Butterly, MD
Rituximab versus Azathioprine for Maintenance in ANCA-Associated Vasculitis
L Guillevin et al New England Journal of Medicine 2014; 371: 1771-1780
This article appeared in the NEJM 3 weeks ago. It caught my eye, as I follow several patients in clinic with ANCA-Associated Vasculitis (AAV) and a patient I saw most recently has experienced a second relapse requiring further adjustments in the immunosuppressant regimen. Background: Granulomatous polyangiitis (GPA, formerly known as Wegener’s), microscopic polyangiitis, and renal limited ANCA-associated vasculitis are the 3 ANCA associated vasculitis variants. Although they differ in their genetics, pathogenesis, and clinical presentation, they share many clinical features and are currently treated similarly. The outcomes of AAV are frequently poor. The mortality is approximately 25% at 5 years and 20% of those who survive develop ESRD. A staged therapy employing induction regimens with Cytoxan and Glucocorticoids, followed by maintenance regimens have been shown to dramatically improve renal and patient survival and therefore have become standard of care. The more recent emergence of Rituximab over the last years as a new therapy for AAV has been the single most important advance in the treatment of AAVs since Cyclophosphamide nearly 40 years ago. Rituximab was first introduced on the rationale that ANCA contributed to pathogenesis and B-cell targeted therapies would reduce ANCA levels and thus ameliorate disease. Two large randomized controlled trials using Rituximab for induction reported in the NEJM (RAVE NEJM; 363:221-232, 2010 and RITUXIVAS NEJM 363:211-220, 2010) showed that Rituximab was equal to Cytoxan for induction therapy. In the majority of patients, disease control was achieved with induction regimens within 3-6 months. However, despite effective induction therapy, a significant proportion of patients go on to relapse resulting in progressive disease and treatment related side effects. Current therapies tend to suppress but not cure disease in most and relapse has been a constant problem in treatment trials. Current evidence supports the use of Azathioprine or Methotrexate with or without glucocorticoids to prevent relapse (NEJM 359; 26: 2790-2803, 2008). However, these agents have limited efficacy and carry risk of treatment related complications. This current article compares Rituximab to Azathioprine as maintenance therapy in relapse prevention. Current Study: This study enrolled 115 patients (87 with GPA, 23 with MPA, and 5 with renal limited AAV). Patients achieved remission using a Cytoxan-Glucocorticoid prior to randomization. Randomization and protocol for the study are shown in Figure 1 page 1775. 58 patients were treated with Azathioprine (AZA) and 57 were treated with Rituximab. Patients in the AZA group received 2 mg/kg/day thru month 12, 1.5 mg/kg thru month 18, and then 1 mg/kg/day thru the end of 22 months. Those randomized to Rituximab received 500 mg on day 0 and 14, then at 6 12, and 18 months. Demographics and clinical characteristics of the groups are shown in Table 1 page 1776. Mean ages were similar at 56 and 54 years. 40/58 (69%) patients in the AZA group and 47/57 (82%) in the Rituximab group had GPA. 26% of those in the AZA group and 14% of those in the Rituximab group had MPA, and the remainder in each treatment group had Renal-limited AAV. Roughly 80% in each group had newly diagnosed disease with approximately 20% in each group with relapsing disease. Organ involvement was similar between the groups. The GFR tended to be better in the Rituximab treated patients but did not reach statistical significance (p 0.06). Approximately 95% in each group were ANCA positive. Both the cumulative CTX given for induction (6.9 versus 7.2 grams) and Prednisone dosing were similar between the groups. Remission was obtained at a mean of 4.6 months in each treatment arm. Findings: The primary endpoint followed was the percentage of patients with major relapse defined as reappearance or worsening of disease with a Birmingham Vasculitis Activity Score (BVAS) > 0 and involvement of at least 1 major organ. Kaplan-Meier Curves for Probability of remaining free of relapse are shown in Figure 2 page 1777. The effect on the primary outcome was striking and at month 28, major relapse had occurred in 17 patients in the AZA group (29%) and in 3 patients (5%) in the rituximab group. The Hazard ratio for relapse was 6.61 in the AZA group compared to patients treated with Rituximab. The frequency of severe adverse events was similar between the groups (25 in each group). Eight in the AZA group versus 11 in the Rituximab group had severe infections. Conclusions: Although prior studies have demonstrated effective remission-induction agents, the best strategy for maintaining remission remains unclear. Rituximab maintenance therapy, at least in patients with PR-3 ANCA, led to clear benefit in this study. Patients receiving Rituximab had a reduction in relapses of nearly 6 fold. As the study includes patients only with CTX induction, it does not directly inform us on patients with Rituximab induction. Additionally, no cost effectiveness data is included, and a better understanding of the benefits of relapse prevention (ie hospitalizations, cost of further induction, worsening CKD or development of ESRD) would all be important and may offset some of the additional cost of therapy in the Rituximab group. However, this study is an important advance and provides further evidence of effectiveness of Rituximab when used for induction or for maintaining remission. However, the unmet need for curative therapy remains.[box]
[divider]
Clinic Corner
Ambulatory Clinic Corner Want more autonomy in the clinic? Did you ever wonder at what point clinic attendings can stop following residents into the room? Like most things, it depends. Medicare has created something known as the Primary Care (PC) Exception, permitting 4:1 resident:clinic attending ratios and not requiring attendings to see patients with their own eyes for more routine visits – i.e., no higher than a Level 3 visit. But to bill a Level 4 Return Visit,* which pays 15-20% higher and more often accurately reflects the complexity of the patients you see, the PC Exception does NOT apply. So don’t take being followed as an affront, but as an acknowledgement of just how difficult caring for your patients can be (balanced against a desire to keep things moving and avoid having to make you wait to be precepted). The PC Exception also does not apply for supervision of trainees who have “completed less than six months in an approved GME Residency Program” (e.g., interns). So in past years, the point when an intern could stop being followed could be arbitrarily determined by the calendar, regardless of how much or little time one actually spent in clinic. However, beginning a few years ago with Duke’s participation in a multi-institutional pilot of milestone-based graduation of interns to more autonomous practice in the clinic, there has been a desire to make this process more rational – and use the requested three mini-CEXs a year in the clinic to help do that. Over this month and into early 2016, the clinic sites will be working to get the interns their magic three observations. But we also wanted to make it worth the while of JARs and SARs, too. To reward those residents who continue to volunteer themselves for the requested three (3) Ambulatory Mini CEX observations -- and who were rated to be at or above their expected level for their stage of training -- with continued advancement in the level of their autonomy in clinic, as well. This one-pager summarizes the different levels, which includes being able to batch two signouts together if there is a queue and the first patient is routine. So thank you to all the residents and attendings who have participated in the Ambulatory Mini CEXs completed to date this year – residents, for inviting preceptors into your clinic rooms to observe what you do well, and offer pointers on how you can become even better; and attendings, for taking the time to provide feedback (and enter it into MedHub). *In case you were curious, billing a Level 4 Return Visit (99214) requires documentation reflecting 2 of 3 of following: -detailed history (HPI-4+ elements for acute/3+ for chronic diseases, plus 2-9 point ROS, AND review of either PMH, SH, or FH); Wanted: Future leaders in Ambulatory Care Have you thought about how your training provides the kinds of knowledge and skills you'll need in your career? For those interested in primary care or whose future practice will be predominantly in ambulatory settings, the two-year Ambulatory Care Leadership Track (ACLT) can help you prepare by providing you with broader ambulatory clinical exposure, plus additional experiences in clinical teaching, advanced EBM, communication, and leadership and advocacy. Created by Larry Greenblatt and now led by Dani Zipkin, who works closely with the Ambulatory Chief Resident, our beloved Bonike, the ACLT is now accepting applications for 2014-15. We encourage you to consider applying, and to talk to any of the residents currently in the program (Claire Kappa, Brice Lefler, Adrienne Belasco, Matt Atkins, Ryan Jessee, Amy Little Jones, and Dinushika Mohottige) to see if the ACLT is the right choice for you. Four spots will be opening in the 2015-16 academic year for rising JARs (interested SARs should reach out to Dani and Alex Cho). And we should emphasize again that the track was designed not only for residents interested in primary care, but also for those of you who are interested in ambulatory subspecialty careers. We can also promise you social events and camaraderie with like-minded residents and faculty, organized by Sharon Rubin and others. If interested or if you have questions please contact Dani, Alex, Bonike, or Larry. A brief, one-page application will be due Wednesday, December 31. ACLT application form - 2014-15QI Corner
![Aaron Mitchell, MD](http://news.medicine.duke.edu/wp-content/uploads/2014/08/PREFERRED_Mitchell_Aaron_6228-682x1024.jpg)
From the Chief Residents
Grand Rounds
Fri., Dec. 5: M&M, Dr. Aaron Mitchell
Noon Conference
Date | Topic | Lecturer | Time | Vendor |
12/1/14 | SAR Series: Good, Bad, Ugly, and Hilarious of Contemporary Healthcare Politics | Nick Rohrhoff | 12:15/2002 | Mediterra |
12/2/14 | MED PEDS INTERVIEW/ G Briefing Session | Lunch w/applicants | 12:00/MedRes | |
12/3/14 | MATCH DAY | Fun Lunch | 12:00/Room 2002 | China King |
12/4/14 | SAR Emergency Series- Transfusion Overview | Venu Reddy | 12:15/2001 | Chick-Fil-A |
12/5/14 | Interview Day | Lunch w/ applicants | 12:00/MedRes |
From the Residency Office
Congratulations to Lynsey Michnowicz!
Please join the MedRes office team in congratulating Lynsey Michnowicz on her recent promotion! As of December 1, Lynsey is now Program Coordinator for the Internal Medicine, Med-Psych and Infectious Disease training programs! Lynsey has been an amazing addition to our team and we are very fortunate to have her in this new position!ABIM Summer 2015 Examination Dates
Please see the attached flyer for information on dates and registration!Stead Research Grant RFA
On behalf of the Stead Scholarship Committee, we would like to announce a Request for Applications for a clinical or translational research project involving a team of Internal Medicine, Med-Peds, and/or Med-Psych residents under the leadership of a faculty mentor in the Department of Medicine. The RFA is attached. We are grateful to the leadership of the Stead Scholarship Committee (Chris Woods, Karen Alexander and Ravi Karra) for this generous initiative to promote and support team-research by our residents. Best regards to all, Murat and AimeeACP Abstracts Due!
Please find attached the information to submit abstracts by December 12, 2014 of your scholarly activities (case reports, research, QI projects) American College of Physicians NC Chapter Meeting Date: Feb 13,14 2015 Where: Sheraton RTP Submissions for abstracts due 12/12/14 http://www.acponline.org/about_acp/chapters/nc/abstract_comp.htm Wishing you all success with your projects ! Murat and AimeeInformation/Opportunities
Sign up to receive a complimentary e-subscription to The American Journal of Medicine in 2015! All you have to do is to complete the online form by December 8, 2014. The subscription starts in January. Internal Medicine Opportunities Physician Recruiting Services - Beck & FieldUpcoming Dates and Events
December 3, 2014 - SAR Match Party
December 13, 2014 - DoM Holiday Party
February 18, 2015 - Duke vs UNC @ Tyler's Tap Room
February 27, 2015 - Charity Auction
March 3, 2015 - Duke vs UNC
Useful links
- https://intranet.dm.duke.edu/influenza/SitePages/Home.aspx
- http://duke.exitcareoncall.com/.
- Main Internal Medicine Residency website
- Main Curriculum website
- Ambulatory curriculum wiki
- Department of Medicine
- Confidential Comment Line Note: ALL submissions are strictly confidential unless you chose to complete the optional section requesting a response