TY - JOUR

T1 - Mycophenolate Mofetil Versus Cyclophosphamide for Remission Induction in Childhood Polyarteritis Nodosa: An Open-Label, Randomized, Bayesian Noninferiority Trial

AU - Brogan, Paul A.

AU - Arch, B.

AU - Hickey, H.

AU - Anton, J.

AU - Iglesias, E.

AU - Baildam, E,

AU - Mahmood, K.

AU - Cleary, G.

AU - Moraitis, E.

AU - Papadopoulou, C.

AU - Beresford, M.W.

AU - Riley, P.

AU - Demir, S.

AU - Ozen, S.

AU - Culeddu, Giovanna

AU - Hughes, Dyfrig

AU - Dolezalova, P.

AU - Hampson, L.

AU - Whitehead, J.

AU - Jayne, D.

AU - Ruperto, N.

AU - Tudor-Smith, Catrin

AU - Eleftheriou, D.

N1 - Sponsorship was provided by University College London. Funding was provided by Versus Arthritis (grant number 20094), Vasculitis UK, and the Lauren Currie Twilight Foundation. The lead clinical trial unit was the Liverpool Clinical Trials Centre (LCTC). We also acknowledge support from the Pediatric Rheumatology International Trial Organisation (PRINTO), and Great Ormond St Hospital Charity.

PY - 2021/9

Y1 - 2021/9

N2 - ObjectiveCyclophosphamide (CYC) is used in clinical practice off-label for induction of remission of childhood polyarteritis nodosa (cPAN). Mycophenolate mofetil (MMF) might offer a less toxic alternative: we explored their relative effectiveness in a randomised controlled trial (RCT).MethodsInternational, open-label, Bayesian, RCT investigating the relative effectiveness of MMF and CYC for remission induction in cPAN. Eleven newly-diagnosed patients were randomised (1:1) to MMF or intravenous-CYC; all received the same glucocorticoid regimen. The primary endpoint was remission within 6-months whilst compliant with glucocorticoid taper. Bayesian distributions for remission rates were established a priori for MMF and CYC by experienced clinicians, and updated to posterior distributions on trial completion.ResultsBaseline disease activity/features were similar between groups. The primary remission endpoint occurred in 4/6 patients (67%) in the MMF group and 4/5 patients (80%) in the CYC group. Time to remission was shorter in the MMF group (median 7.4 weeks versus 17.5 weeks for CYC). No relapses occurred in either group within 18-months. Two serious infections were probably related to MMF. Physical and psychosocial quality-of-life scores were superior in the MMF group compared to CYC at 6-and 18-months. Combining the prior expert opinion with results from MYPAN provided posterior estimates of remission of 71% (90% CrI 51-83%) for MMF; and 75% (90% CrI 57-86%) for CYC.ConclusionTaking the prior opinion and the study results together, rates of remission induction in cPAN on MMF and CYC are similar, and MMF might be associated with better health-related quality of life than CYC.

AB - ObjectiveCyclophosphamide (CYC) is used in clinical practice off-label for induction of remission of childhood polyarteritis nodosa (cPAN). Mycophenolate mofetil (MMF) might offer a less toxic alternative: we explored their relative effectiveness in a randomised controlled trial (RCT).MethodsInternational, open-label, Bayesian, RCT investigating the relative effectiveness of MMF and CYC for remission induction in cPAN. Eleven newly-diagnosed patients were randomised (1:1) to MMF or intravenous-CYC; all received the same glucocorticoid regimen. The primary endpoint was remission within 6-months whilst compliant with glucocorticoid taper. Bayesian distributions for remission rates were established a priori for MMF and CYC by experienced clinicians, and updated to posterior distributions on trial completion.ResultsBaseline disease activity/features were similar between groups. The primary remission endpoint occurred in 4/6 patients (67%) in the MMF group and 4/5 patients (80%) in the CYC group. Time to remission was shorter in the MMF group (median 7.4 weeks versus 17.5 weeks for CYC). No relapses occurred in either group within 18-months. Two serious infections were probably related to MMF. Physical and psychosocial quality-of-life scores were superior in the MMF group compared to CYC at 6-and 18-months. Combining the prior expert opinion with results from MYPAN provided posterior estimates of remission of 71% (90% CrI 51-83%) for MMF; and 75% (90% CrI 57-86%) for CYC.ConclusionTaking the prior opinion and the study results together, rates of remission induction in cPAN on MMF and CYC are similar, and MMF might be associated with better health-related quality of life than CYC.

KW - Polyarteritis nodosa

KW - Child

KW - Randomised control trial

KW - Bayesian

KW - Mycophenolate mofetil

KW - Cyclophosphamide

U2 - 10.1002/art.41730

DO - 10.1002/art.41730

M3 - Article

VL - 73

SP - 1673

EP - 1682

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 9

ER -