Correlative Metrics of Adherence to Immunosuppression in Upper Extremity Transplant Recipients - Pittsburgh Experience
Firuz G. Feturi, PhD1, Vincent Chavanon, MD1, Jaimie Shores, MD2, Gerald Brandacher, MD2, Andrew Lee, MD2, Joseph Losee, MD1, Kia Washington, MD1, Mario G. Solari, MD1, Raman Venkataramanan, PhD1, Vijay Gorantla, MD3, Alexander M. Spiess, MD1.
1University of Pittsburgh, Pittsburgh, PA, USA, 2John Hopkins University, Baltimore, MD, USA, 3Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
Patients' adherence to their immunosuppressive regimen is vital for favorable immunologic and functional outcomes. Poor medication adherence MA remains a major cause of preventable graft rejection. Self- and physician report are the common methods used to assess adherence in clinical settings, they are often inaccurate and may underestimate nonadherence. Data related to MA and accurate method to assess MA in upper extremity transplants (UETs) have not been adequately evaluated and are thus not available. We present our experience of MA monitoring utilizing an objective and subjective battery of measures including patient, protocol (drugs/endogenous materials level measurement), graft, and physician related metrics.
Between March 2009 and September 2010, 5 patients received 8 UETs (2 unilateral, 3 bilateral) with a mean follow-up of 2.3 years. Post-transplant adherence to immunosuppression was evaluated using subjective and objective metrics. Patients completed Morisky Medication Adherence Questionnaire (MMAQ8). Patient records were reviewed retrospectively to assess intra-subject variability (ISV) of tacrolimus trough levels, number of blood draws and therapy visits, biopsy results, donor specific antibodies (DSA), cellular mediated immunity (Cylex). ISV of trough levels was determined by coefficient of variation (CV, %) of trough levels taken between 6 and 18 months post-transplant. Median CV of the overall cohort is the threshold of variability 28.3 (range 23.4-43.3). Total adherence scores were correlated with the outcomes (# of severe rejection episodes, and Carroll (function) and DASH (disability) test scores).
High intra-subject variability 32 (range 19-40.7) in tacrolimus troughs was observed in all patients during the first six months. All patients experienced acute rejection (AR) episodes during the first 3 months. Patients 2 and 3 reported high adherence, while patients 1, 4 and 5 were moderately adherent, by self-reported MMAQ8 standards. Surrogate trends of fluctuating tacrolimus troughs with a CV 42.4, more frequent monitoring, DSA persistently greater >2000 MFI, greater variability in Cylex data, and repetitive AR with a trend toward higher Banff grades mandating increased immunosuppression indicate non-adherence in Patient 1. He had allograft failure, and underwent explanation 4 years post-transplant. The fluctuating tacrolimus troughs with a CV 30 and repetitive AR episodes indicate low adherence in Patient 2. While Patients 3, 4 and 5 have demonstrated adherence to medication as evidenced by relatively stable tacrolimus troughs with CV 24, 28, and 23, less frequent monitoring, and a fewer number AR episodes. Total adherence scores were significantly correlated with the outcomes (r=-0.9). Among these metrics, ISV of trough levels was significantly correlated with the outcomes (r=0.7).
Currently, no teams actively measure MA in UETs. Prevalence of non-adherence NA may thus be under-detected/reported. This study shows that post-operative assessment of patient behavior combined with selected clinical metrics including ISV of tacrolimus trough levels, number of blood draws and therapy visits, biopsy results, with self and physician report can better estimate
NA and identify at-risk patients, ensuring timely intervention with graft-sparing measures that improve outcomes. ISV of tacrolimus trough levels should be considered in the current monitoring protocols due to its relationship with adherence and to graft outcome.
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