Buprenorphine, a novel opioid with complex pharmacology, is effective for treating pain and is qualitatively safer than high-dose full agonist opioid therapy; but transitioning to buprenorphine can be technically complex and carries some risk of precipitated withdrawal. We report our clinic's experience converting 36 patients with sickle cell disease (SCD) from full agonist opioids to buprenorphine using a method developed in the past 10 years. Thirty of these patients were induced using a standard outpatient protocol and six were induced during medical admissions. Typically, patients were on high-dose chronic opioid therapy (COT) with inadequate response, and often with very high acute care utilization. Unlike prior case series, the method of induction, dosing, and management of withdrawal are detailed, as are postinduction adverse events. There were seven adverse events in the first 3 days following standard induction, and two of which were judged to be definitely related to the induction but none with any lasting sequelae. At 6 months follow-up, five participants had discontinued buprenorphine (16.67%), and overall acute care visits dropped from a mean of 10.50 (SD 11.35) in the 6 months pre-induction to 2.89 (SD 3.40) in the 6 months post-induction. In an appropriately interdisciplinary care setting, buprenorphine shows promise as a safe alternative to COT with early evidence of benefit for high-utilizing patients with SCD. | INTRODUCTIONSickle cell disease (SCD) is a genetic hematologic disorder that affects between 80 000 and 100 000 individuals in the United States and leads to severe morbidity and early mortality. [1][2][3][4][5][6] Acute painful crises are the most common complications of SCD and drive a large number of acute care visits and hospitalizations. [7][8][9][10] In addition, SCD pain can evolve into a chronic pain condition with poorly understood physiology. [11][12][13][14][15][16] Half or more of adult SCD patients in the United States likely meet criteria for chronic pain. 11,17 People living with SCD consistently describe pain as the greatest detriment to their quality of life, and an optimal pain management strategy remains unclear. 18 Numerous studies show that patients and healthcare providers are dissatisfied with the quality of SCD pain management. [18][19][20] Disease-modifying therapies that prevent acute crises have little effect on chronic SCD pain. 16,21 The evidence base for management of chronic pain in SCD is sparse, 22 but chronic opioid therapy (COT) is one major modality. Clinical trials of opioids for chronic non-cancer pain (CNCP) support efficacy relative to placebo, but also frequently fail to produce clinically significant improvements. Risks emerge with

Background: The management of pain in adults with sickle cell disease (SCD) is complex, with the intermingling of both acute vaso-occlusive events and chronic daily pain. Sixty percent of adults with SCD suffer with every day chronic pain. In patients with frequent acute visits we use aggressive disease modifying therapy to decrease the risk of VOC yet there remains a subset of patients who continue to have frequent acute visits for pain. In addition, there are patients maintained on high doses of oral opioids as outpatients who continue to have high levels of daily pain. There is little data that escalating doses of opioids is associated with benefit, yet significant data to support that higher doses are associated with harms. We consider these to be cases of opioid failure. Identifying therapies for these patients that improve quality of life is essential. Buprenorphine is a partial mu opioid receptor agonist and kappa antagonist, and has a very high affinity for the mu receptors, with an elimination half-life of 28-37 hours for the sublingual administration. The reduced risk of overdose, lower risk for misuse, diminished withdrawal symptoms, and blunting of opioid craving make it an appealing alternative to full opioid agonists in a subset of patients with SCD who continue to have significant pain or are unable to wean off of ineffective opioid therapy. The purpose of this report is to describe our experience converting patients with SCD and chronic pain from chronic opioid therapy to buprenorphine. Methods: Routine clinical care in our clinic includes offering buprenorphine transition to patients on chronic opioid therapy with numerous acute care visits despite the use of disease modifying therapy; or patients on chronic opioid therapy reporting significant ongoing pain. Patients are typically weaned to lower opioid doses (goal 90 oral morphine equivalents) prior to the planned induction with buprenorphine. Once patients are at the goal dose, they are asked to hold opioids for 12-24 hours prior to presentation so that they are in at least mild opioid withdrawal prior to their first dose of buprenorphine to avoid precipitated withdrawal. The patient is assessed with the Clinical Opiate Withdrawal Scale (COWs) and if their score is 5 or higher they are administered their first dose of sublingual buprenorphine. If COWs scores are less than 5, buprenorphine is not initiated and the subject is asked to return the following day or earlier if withdrawal symptoms begin. Patients are reassessed with the COWs and dosed with buprenorphine hourly until withdrawal has ceased. The dose needed to minimize withdrawal is considered the working total daily dose. Patients are sent home and return the next day to start their once daily dose of buprenorphine. Urine toxicology testing is done the day of planned induction. Data on acute visits 6 months prior and 6 months post induction and on complications associated with induction were pulled from the electronic health record. Results: 21 patients have been converted from full agonist opioids to buprenorphine from 3/2015-6/1/2018. The average age of the patients at the time of induction was 36.1 years (SD 9.1), 62% were female. Sixteen (76 %) of the patients had sickle cell anemia, the remainder had variant genotypes. The mean dose (in morphine equivalents) of full agonist opioid that patients were on prior to weaning of opioids was 196.8 mg (SD 222.7) and just prior to induction was 85 mg (SD 70 mg) with a range of 11.4 to 315 mg. Seventeen patients tolerated the induction without any complications, 2 patients had abdominal cramps but were successfully converted, 2 patients has adverse reactions (1 had numbness of tongue and 1 with worsening of asthma) and buprenorphine was stopped. Of the 19 patients successfully converted, two chose to stop buprenorphine and resume taking full opioid agonists. For the 13 patients with 6 months of follow-up post induction, the median number of acute care visits prior to induction was 12.5 and post was 4.0 (Figure). Conclusions: Adults with sickle cell disease on chronic full agonist opioid therapy can be safely converted to buprenorphine. Acute care utilization has dropped significantly for patients post induction. Assessment of patient reported outcomes such as quality of life and pain interference are being collected. Buprenorphine appears to be a safe and effective medication in the management of pain in adults with SCD. Figure. Figure. Disclosures Lanzkron: PCORI: Research Funding; GBT: Research Funding; Prolong: Research Funding; Pfizer: Research Funding; selexys: Research Funding; NHLBI: Research Funding; HRSA: Research Funding; Ironwood: Research Funding.