1. Pneumocystis prophylaxis in ANCA vasculitis
Robert Hunter
Wellcome Trust Clinical Research Career Development Fellow
Honorary Consultant In Renal

2. Pneumocystis prophylaxis in ANCA vasculitis
Overview:
Risk of PCP in ANCA vasculitis
A case
Prophylaxis regimens
Trimethoprim-sulfamethoxazole desensitisation
Questions:
Who should receive PCP prophylaxis?
What should we do when patients are allergic to TMP-SMX?

3. PCP in ANCA vasculitis Jarrousse (1993) Guillevin (1997)
Reinhold-Keller (2000)
Bligny (2002)
Booth (2003)
Charles (2011)
Guillevin (2014)
Edinburgh registry
PCP in ANCA vasculitis
We have 1012 patient-years and 2 cases = 0.2 cases per 100 patient-years
Consider epidemic vs. sporadic
Outbreak in 2015 in Aberdeen, Birmingham, Cambridge (e.g. 4 cases in Aberdeen)
Jarrousse = GPA without prophylaxis
Booth = London, renal disease only
Guillevin (2014) = MAINRITSAN
Charles = French, rituximab only

4. Case
Case of PCP in patient with AAV during maintenance rituximab. Role of T-S desensitisation discussed.

5. PCP prophylaxis BSR / BHPR EULAR / ERA CANVAS Indication: 1st-line:
CYC (grade B)
other induction with high- dose GC (grade C)
CYC
CYC (grade C)
RTX (grade C)
1st-line:
TMP-SMX 960 mg thrice- weekly
960 mg alt days
480 mg daily
2nd-line:
pentamidine or dapsone
pentamidine (but NOT routinely)
Options: 1) trimethoprim-sulfamethoxazole (daily, thrice-weekly)
2) dapsone 100 mg daily
3) dapsone 100 mg + pyrimethamine 25 mg twice-weekly
4) atovaquone 750 mg daily
5) pentamidine 300 mg nebulised monthly
NB dose-adjustments in renal failure and potential interaction between methotrexate and TMP-SMX

6. TMP-SMX prophylaxis TMP-SMX is effective at preventing PCP
(Stern et al., Cochrane Rev, 2016)
Adverse reactions lead to discontinuation of TMP-SMX in ~20%
Desensitisation is more effective than re-challenge
(Lin et al., Cochrane Rev, 2007)
Our desensitisation regime:
96 mg daily for 3 days (= 1 ml of 480 mg / 5 ml liquid)
192 mg for 3 days (= 2 ml)
288 mg for 3 days (= 3 ml)
384 mg for 3 days (= 4 ml)
480 mg daily (= 5 ml or convert to tablet)
NNT = 19 in non-HIV population with control event rate = 6% = Stern et al, Cochrane 2016
Desensitation is better than re-challenge: NNT = 7 to prevent T-S discontinuation (in HIV population: Lin et al., Cochrane 2007)
Reference for discontinuation in 20% is in introduction to Cochrane review 2007 and also Stegeman (NEJM, 1996)
Classic protocols last 48 hrs – 5 days (including the three studies reviewed by the 2007 Cochrane review)

7. Our answers Who should receive PCP prophylaxis?
everybody during induction (not only cyclophosphamide)
…and for months-years thereafter
inclusive (vs. risk-oriented) prescription
possible immunomodulatory benefit of TMP-SMX
(Stegeman et al., NEJM 1996; Salmela et al., Rheumatology, 2017)
What should we do when patients are allergic to TMP-SMX?
consider immune context
desensitise (13-day regime, steroids, anti-histamines, close monitoring)

8. Acknowledgments Neeraj Dhaun (Bean) David Kluth Eve Miller-Hodges
BHF Intermediate Fellow & Honorary Consultant Nephrologist
David Kluth
Senior Lecturer in Nephrology & Honorary Consultant Nephrologist
Eve Miller-Hodges
Specialist Registrar in Nephrology & Vasculitis Fellow
Tariq Farrah
MRC Clinical Fellow
Jin Werne Hah
Renal Pharmacist
Sadaf Arshad
@renalrob