TBD Meeting (5367-19)

FORT LAUDERDALE, FLA. — A dedicated, 24-hour, 7-day-a-week sickle cell inpatient observation unit staffed by a multidisciplinary care team significantly reduced inpatient admissions and emergency department visits per patient, according to an analysis of a Philadelphia program.

“These findings confirm the need for an individualized approach to treatment,” Sanaa Rizk, MD, director of the hereditary anemia program at Thomas Jefferson University Hospital, Philadelphia, said at the annual meeting of the Foundation for Sickle Cell Disease Research. “The potential strength of a multidisciplinary approach and personalized interventions toward high-utilizing subpopulations may offer the greatest impact.”

The study evaluated what Dr. Rizk called “the second clinical transformation” in care of sickle cell disease patients, which Thomas Jefferson University implemented in 2015. The comprehensive sickle cell center first opened in 2003, and the first transformation in November 2013 consisted of opening a four-bed sickle cell day unit to treat uncomplicated sickle cell vaso-occlusive crises with personalized pain treatment protocols (including IV fluids and opioids). It was staffed by a nurse practitioner, medical assistant, and two registered nurses from 8 a.m. to 5 p.m.

The second transformation transferred care to the inpatient observation unit on the hospital floor with access to 12 patient beds. A sickle cell nurse practitioner sees patients for same-day appointments, conducts sick visits, performs outreach, and handles follow-up with patients. The rest of the multidisciplinary team includes hospitalists, hematologists, internists, and a social worker who performs weekly inpatient rounds and meets monthly with ED leaders and pharmacists.

With the first transformation, ED visits per patient fell from 3.67 to 2.14 a year (P less than .001), and inpatient admissions per patient fell from 1.33 to 0.63 (P less than .0001), Dr. Rizk reported.

The second transformation reduced those per-patient rates even further, to 0.47 ED visits (P less than .01) and 0.29 inpatient admissions (P less than .001), she said.

“The expansion of the service reduced admissions and ED use significantly,” Dr. Rizk said.

She added that a subanalysis of the high-utilizer subgroup showed a decrease in average total medical charges by approximately $100,000/patient per year.

Dr. Rizk reported having no relevant financial disclosures.

SOURCE: Rizk S et al. FSCDR 2019, Abstract JSCDH-D-19-00049.

FORT LAUDERDALE, FLA. — A dedicated, 24-hour, 7-day-a-week sickle cell inpatient observation unit staffed by a multidisciplinary care team significantly reduced inpatient admissions and emergency department visits per patient, according to an analysis of a Philadelphia program.

“These findings confirm the need for an individualized approach to treatment,” Sanaa Rizk, MD, director of the hereditary anemia program at Thomas Jefferson University Hospital, Philadelphia, said at the annual meeting of the Foundation for Sickle Cell Disease Research. “The potential strength of a multidisciplinary approach and personalized interventions toward high-utilizing subpopulations may offer the greatest impact.”

The study evaluated what Dr. Rizk called “the second clinical transformation” in care of sickle cell disease patients, which Thomas Jefferson University implemented in 2015. The comprehensive sickle cell center first opened in 2003, and the first transformation in November 2013 consisted of opening a four-bed sickle cell day unit to treat uncomplicated sickle cell vaso-occlusive crises with personalized pain treatment protocols (including IV fluids and opioids). It was staffed by a nurse practitioner, medical assistant, and two registered nurses from 8 a.m. to 5 p.m.

The second transformation transferred care to the inpatient observation unit on the hospital floor with access to 12 patient beds. A sickle cell nurse practitioner sees patients for same-day appointments, conducts sick visits, performs outreach, and handles follow-up with patients. The rest of the multidisciplinary team includes hospitalists, hematologists, internists, and a social worker who performs weekly inpatient rounds and meets monthly with ED leaders and pharmacists.

With the first transformation, ED visits per patient fell from 3.67 to 2.14 a year (P less than .001), and inpatient admissions per patient fell from 1.33 to 0.63 (P less than .0001), Dr. Rizk reported.

The second transformation reduced those per-patient rates even further, to 0.47 ED visits (P less than .01) and 0.29 inpatient admissions (P less than .001), she said.

“The expansion of the service reduced admissions and ED use significantly,” Dr. Rizk said.

She added that a subanalysis of the high-utilizer subgroup showed a decrease in average total medical charges by approximately $100,000/patient per year.

Dr. Rizk reported having no relevant financial disclosures.

SOURCE: Rizk S et al. FSCDR 2019, Abstract JSCDH-D-19-00049.

FORT LAUDERDALE, FLA. — A dedicated, 24-hour, 7-day-a-week sickle cell inpatient observation unit staffed by a multidisciplinary care team significantly reduced inpatient admissions and emergency department visits per patient, according to an analysis of a Philadelphia program.

“These findings confirm the need for an individualized approach to treatment,” Sanaa Rizk, MD, director of the hereditary anemia program at Thomas Jefferson University Hospital, Philadelphia, said at the annual meeting of the Foundation for Sickle Cell Disease Research. “The potential strength of a multidisciplinary approach and personalized interventions toward high-utilizing subpopulations may offer the greatest impact.”

The study evaluated what Dr. Rizk called “the second clinical transformation” in care of sickle cell disease patients, which Thomas Jefferson University implemented in 2015. The comprehensive sickle cell center first opened in 2003, and the first transformation in November 2013 consisted of opening a four-bed sickle cell day unit to treat uncomplicated sickle cell vaso-occlusive crises with personalized pain treatment protocols (including IV fluids and opioids). It was staffed by a nurse practitioner, medical assistant, and two registered nurses from 8 a.m. to 5 p.m.

The second transformation transferred care to the inpatient observation unit on the hospital floor with access to 12 patient beds. A sickle cell nurse practitioner sees patients for same-day appointments, conducts sick visits, performs outreach, and handles follow-up with patients. The rest of the multidisciplinary team includes hospitalists, hematologists, internists, and a social worker who performs weekly inpatient rounds and meets monthly with ED leaders and pharmacists.

With the first transformation, ED visits per patient fell from 3.67 to 2.14 a year (P less than .001), and inpatient admissions per patient fell from 1.33 to 0.63 (P less than .0001), Dr. Rizk reported.

The second transformation reduced those per-patient rates even further, to 0.47 ED visits (P less than .01) and 0.29 inpatient admissions (P less than .001), she said.

“The expansion of the service reduced admissions and ED use significantly,” Dr. Rizk said.

She added that a subanalysis of the high-utilizer subgroup showed a decrease in average total medical charges by approximately $100,000/patient per year.

Dr. Rizk reported having no relevant financial disclosures.

SOURCE: Rizk S et al. FSCDR 2019, Abstract JSCDH-D-19-00049.

FORT LAUDERDALE, FLA. — Researchers have developed an assay that can be used in noninvasive prenatal testing (NIPT) of cell-free fetal DNA present in maternal blood to identify sickle cell disease without using paternal DNA, which could provide an alternative to other invasive methods, according to results of a pilot study.

Richard Mark Kirkner/MDedge News

The novel NIPT assay had a sensitivity greater than 98% and a specificity greater than 99% in early-phase analysis, Vivien A. Sheehan, MD, PhD, of Baylor College of Medicine, Houston, reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“Noninvasive prenatal testing is a safe and affordable alternative to chorionic villus sampling or amniocentesis and can be performed earlier in pregnancy,” Dr. Sheehan said. “There is a lot of potential for the growth of this test and its impact not only in this country, but worldwide.”

The NIPT uses cell-free fetal DNA from the pregnant mother’s peripheral blood.

“We know that fetal DNA is present in maternal blood and can comprise about 10% by the 10th week of gestation, and it increases as pregnancy progresses,” Dr. Sheehan said.

Maternal alleles from the baby and mother, as well as paternal alleles from the baby, can be identified in maternal blood. “By analyzing cell-free DNA in maternal blood via next-generation sequencing, we can determine fetal disease status,” she said.

Dr. Sheehan noted some reports have supported the use of NIPT for identifying trisomy and aneuploidy, but NIPT has encountered some challenges in identifying autosomal recessive disorders such as sickle cell disease.

To accomplish this, researchers at Baylor and test developer BillionToOne, developed a novel sequencing-based molecular counting strategy that can help measure the ratio of mutant versus normal alleles, Dr. Sheehan said.

The results obtained to date indicate that the assay reliably detects fetal sickle cell disease status when the fetal fraction is as low as 5%, the same limit as aneuploidy NIPT.

The method uses a commercial DNA extraction kit to isolate and purify cell-free fetal DNA from a single blood draw, then performs sickle cell disease NIPT assays using proprietary reagents, Dr. Sheehan explained. The protocol includes bioinformatic analyses that are used to determine hemoglobin S (HbS) mutation ratio and fetal disease status.

The pilot study had two phases. In the first phase, which has been completed, researchers sought to optimize the beta-globin gene probes using cell-free fetal DNA from compound heterozygote patients with sickle cell disease to establish the expected ratio of HbS mutation.

In the second phase, the researchers validated the test on pregnant women with sickle cell trait or sickle cell disease by performing the assay in maternal samples collected between 10-35 weeks of gestation.

Among the six controls who have sickle cell trait, the NIPT reported no false positives when compared with the state newborn screen results, Dr. Sheehan said. For the one participant with sickle cell anemia, the NIPT and newborn screening concurred on two blood draws, but the NIPT was inconclusive on the first blood draw obtained at 10 weeks’ gestation because of low levels of cell-free fetal DNA.

Overall, the analysis showed an analytical sensitivity greater than 98% and a specificity greater than 99%, even in the absence of paternal DNA, the study found.

BillionToOne developed the test. Dr. Sheehan reported having no financial relationships to disclose.

SOURCE: Sheehan VA et al. FSCDR 2019, Abstract JSCDH-D-19-00048.

FORT LAUDERDALE, FLA. — Researchers have developed an assay that can be used in noninvasive prenatal testing (NIPT) of cell-free fetal DNA present in maternal blood to identify sickle cell disease without using paternal DNA, which could provide an alternative to other invasive methods, according to results of a pilot study.

Richard Mark Kirkner/MDedge News

The novel NIPT assay had a sensitivity greater than 98% and a specificity greater than 99% in early-phase analysis, Vivien A. Sheehan, MD, PhD, of Baylor College of Medicine, Houston, reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“Noninvasive prenatal testing is a safe and affordable alternative to chorionic villus sampling or amniocentesis and can be performed earlier in pregnancy,” Dr. Sheehan said. “There is a lot of potential for the growth of this test and its impact not only in this country, but worldwide.”

The NIPT uses cell-free fetal DNA from the pregnant mother’s peripheral blood.

“We know that fetal DNA is present in maternal blood and can comprise about 10% by the 10th week of gestation, and it increases as pregnancy progresses,” Dr. Sheehan said.

Maternal alleles from the baby and mother, as well as paternal alleles from the baby, can be identified in maternal blood. “By analyzing cell-free DNA in maternal blood via next-generation sequencing, we can determine fetal disease status,” she said.

Dr. Sheehan noted some reports have supported the use of NIPT for identifying trisomy and aneuploidy, but NIPT has encountered some challenges in identifying autosomal recessive disorders such as sickle cell disease.

To accomplish this, researchers at Baylor and test developer BillionToOne, developed a novel sequencing-based molecular counting strategy that can help measure the ratio of mutant versus normal alleles, Dr. Sheehan said.

The results obtained to date indicate that the assay reliably detects fetal sickle cell disease status when the fetal fraction is as low as 5%, the same limit as aneuploidy NIPT.

The method uses a commercial DNA extraction kit to isolate and purify cell-free fetal DNA from a single blood draw, then performs sickle cell disease NIPT assays using proprietary reagents, Dr. Sheehan explained. The protocol includes bioinformatic analyses that are used to determine hemoglobin S (HbS) mutation ratio and fetal disease status.

The pilot study had two phases. In the first phase, which has been completed, researchers sought to optimize the beta-globin gene probes using cell-free fetal DNA from compound heterozygote patients with sickle cell disease to establish the expected ratio of HbS mutation.

In the second phase, the researchers validated the test on pregnant women with sickle cell trait or sickle cell disease by performing the assay in maternal samples collected between 10-35 weeks of gestation.

Among the six controls who have sickle cell trait, the NIPT reported no false positives when compared with the state newborn screen results, Dr. Sheehan said. For the one participant with sickle cell anemia, the NIPT and newborn screening concurred on two blood draws, but the NIPT was inconclusive on the first blood draw obtained at 10 weeks’ gestation because of low levels of cell-free fetal DNA.

Overall, the analysis showed an analytical sensitivity greater than 98% and a specificity greater than 99%, even in the absence of paternal DNA, the study found.

BillionToOne developed the test. Dr. Sheehan reported having no financial relationships to disclose.

SOURCE: Sheehan VA et al. FSCDR 2019, Abstract JSCDH-D-19-00048.

FORT LAUDERDALE, FLA. — Researchers have developed an assay that can be used in noninvasive prenatal testing (NIPT) of cell-free fetal DNA present in maternal blood to identify sickle cell disease without using paternal DNA, which could provide an alternative to other invasive methods, according to results of a pilot study.

Richard Mark Kirkner/MDedge News

The novel NIPT assay had a sensitivity greater than 98% and a specificity greater than 99% in early-phase analysis, Vivien A. Sheehan, MD, PhD, of Baylor College of Medicine, Houston, reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“Noninvasive prenatal testing is a safe and affordable alternative to chorionic villus sampling or amniocentesis and can be performed earlier in pregnancy,” Dr. Sheehan said. “There is a lot of potential for the growth of this test and its impact not only in this country, but worldwide.”

The NIPT uses cell-free fetal DNA from the pregnant mother’s peripheral blood.

“We know that fetal DNA is present in maternal blood and can comprise about 10% by the 10th week of gestation, and it increases as pregnancy progresses,” Dr. Sheehan said.

Maternal alleles from the baby and mother, as well as paternal alleles from the baby, can be identified in maternal blood. “By analyzing cell-free DNA in maternal blood via next-generation sequencing, we can determine fetal disease status,” she said.

Dr. Sheehan noted some reports have supported the use of NIPT for identifying trisomy and aneuploidy, but NIPT has encountered some challenges in identifying autosomal recessive disorders such as sickle cell disease.

To accomplish this, researchers at Baylor and test developer BillionToOne, developed a novel sequencing-based molecular counting strategy that can help measure the ratio of mutant versus normal alleles, Dr. Sheehan said.

The results obtained to date indicate that the assay reliably detects fetal sickle cell disease status when the fetal fraction is as low as 5%, the same limit as aneuploidy NIPT.

The method uses a commercial DNA extraction kit to isolate and purify cell-free fetal DNA from a single blood draw, then performs sickle cell disease NIPT assays using proprietary reagents, Dr. Sheehan explained. The protocol includes bioinformatic analyses that are used to determine hemoglobin S (HbS) mutation ratio and fetal disease status.

The pilot study had two phases. In the first phase, which has been completed, researchers sought to optimize the beta-globin gene probes using cell-free fetal DNA from compound heterozygote patients with sickle cell disease to establish the expected ratio of HbS mutation.

In the second phase, the researchers validated the test on pregnant women with sickle cell trait or sickle cell disease by performing the assay in maternal samples collected between 10-35 weeks of gestation.

Among the six controls who have sickle cell trait, the NIPT reported no false positives when compared with the state newborn screen results, Dr. Sheehan said. For the one participant with sickle cell anemia, the NIPT and newborn screening concurred on two blood draws, but the NIPT was inconclusive on the first blood draw obtained at 10 weeks’ gestation because of low levels of cell-free fetal DNA.

Overall, the analysis showed an analytical sensitivity greater than 98% and a specificity greater than 99%, even in the absence of paternal DNA, the study found.

BillionToOne developed the test. Dr. Sheehan reported having no financial relationships to disclose.

SOURCE: Sheehan VA et al. FSCDR 2019, Abstract JSCDH-D-19-00048.

FORT LAUDERDALE, FLA. – Sickle cell patients who received high-dose crizanlizumab had fewer vaso-occlusive crises (VOCs) than patients on a low-dose regimen a year after stopping the treatment, findings from a real-world follow-up study suggest.

But hospitalization rates and use of other health care resources were similar during and after therapy, regardless of dose, Nirmish Shah, MD, of Duke Health in Durham, N.C., reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“This is our attempt at a real-world study of patients after being in a big study that has good results and what happens to them afterward in regard to VOCs and health care utilization,” Dr. Shah said.

He reported results from the SUCCESSOR trial – a multicenter, retrospective cohort study – that evaluated a subset of 48 adult patients up to a year after they completed the SUSTAIN placebo-controlled phase 2 trial of crizanlizumab, a P-selectin inhibitor designed to control sickle cell pain crises.

In SUSTAIN, researchers evaluated two different dosages of crizanlizumab: 5 mg/kg and 2.5 mg/kg.

In the follow-up study, researchers obtained data from medical records over the study period November 2014 to March 2017. Crizanlizumab was not administered in the 52 weeks following the SUSTAIN trial.

They found that the subset of patients on the high dose of crizanlizumab had annual VOC rates of 2.7, compared with 4.0 among patients on the low dose of the drug. By comparison, VOC rates in SUSTAIN were 1.7 per year for the 5-mg/kg–dose group and 3.2 per year for the 2.5-mg/kg–dose group.

Overall, at least 60% of patients in the follow-up study had at least one hospitalization in the year after SUSTAIN. In the higher-dose group, the rates of hospitalization were similar in both SUSTAIN and SUCCESSOR – 53%. In the lower-dose group, hospitalization rates were 67% and 61% in SUCCESSOR and SUSTAIN, respectively.

“Among the previously treated patients with crizanlizumab, the total number of emergency department visits did seem to be higher in SUCCESSOR,” Dr. Shah said.

The study was limited by its retrospective nature and the fact that full data sets and follow-up were available on only a small number of patients, Dr. Shah said. “It was underpowered for a statistical analysis between groups,” he said. The goal was to determine the drug’s effect after treatment is discontinued, he said.

Dr. Shah reported a financial relationship with Novartis, which is developing crizanlizumab.

SOURCE: Shah N et al. FSCDR 2019, Abstract JSCDH-D-19-00031.

FORT LAUDERDALE, FLA. – Sickle cell patients who received high-dose crizanlizumab had fewer vaso-occlusive crises (VOCs) than patients on a low-dose regimen a year after stopping the treatment, findings from a real-world follow-up study suggest.

But hospitalization rates and use of other health care resources were similar during and after therapy, regardless of dose, Nirmish Shah, MD, of Duke Health in Durham, N.C., reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“This is our attempt at a real-world study of patients after being in a big study that has good results and what happens to them afterward in regard to VOCs and health care utilization,” Dr. Shah said.

He reported results from the SUCCESSOR trial – a multicenter, retrospective cohort study – that evaluated a subset of 48 adult patients up to a year after they completed the SUSTAIN placebo-controlled phase 2 trial of crizanlizumab, a P-selectin inhibitor designed to control sickle cell pain crises.

In SUSTAIN, researchers evaluated two different dosages of crizanlizumab: 5 mg/kg and 2.5 mg/kg.

In the follow-up study, researchers obtained data from medical records over the study period November 2014 to March 2017. Crizanlizumab was not administered in the 52 weeks following the SUSTAIN trial.

They found that the subset of patients on the high dose of crizanlizumab had annual VOC rates of 2.7, compared with 4.0 among patients on the low dose of the drug. By comparison, VOC rates in SUSTAIN were 1.7 per year for the 5-mg/kg–dose group and 3.2 per year for the 2.5-mg/kg–dose group.

Overall, at least 60% of patients in the follow-up study had at least one hospitalization in the year after SUSTAIN. In the higher-dose group, the rates of hospitalization were similar in both SUSTAIN and SUCCESSOR – 53%. In the lower-dose group, hospitalization rates were 67% and 61% in SUCCESSOR and SUSTAIN, respectively.

“Among the previously treated patients with crizanlizumab, the total number of emergency department visits did seem to be higher in SUCCESSOR,” Dr. Shah said.

The study was limited by its retrospective nature and the fact that full data sets and follow-up were available on only a small number of patients, Dr. Shah said. “It was underpowered for a statistical analysis between groups,” he said. The goal was to determine the drug’s effect after treatment is discontinued, he said.

Dr. Shah reported a financial relationship with Novartis, which is developing crizanlizumab.

SOURCE: Shah N et al. FSCDR 2019, Abstract JSCDH-D-19-00031.

FORT LAUDERDALE, FLA. – Sickle cell patients who received high-dose crizanlizumab had fewer vaso-occlusive crises (VOCs) than patients on a low-dose regimen a year after stopping the treatment, findings from a real-world follow-up study suggest.

But hospitalization rates and use of other health care resources were similar during and after therapy, regardless of dose, Nirmish Shah, MD, of Duke Health in Durham, N.C., reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“This is our attempt at a real-world study of patients after being in a big study that has good results and what happens to them afterward in regard to VOCs and health care utilization,” Dr. Shah said.

He reported results from the SUCCESSOR trial – a multicenter, retrospective cohort study – that evaluated a subset of 48 adult patients up to a year after they completed the SUSTAIN placebo-controlled phase 2 trial of crizanlizumab, a P-selectin inhibitor designed to control sickle cell pain crises.

In SUSTAIN, researchers evaluated two different dosages of crizanlizumab: 5 mg/kg and 2.5 mg/kg.

In the follow-up study, researchers obtained data from medical records over the study period November 2014 to March 2017. Crizanlizumab was not administered in the 52 weeks following the SUSTAIN trial.

They found that the subset of patients on the high dose of crizanlizumab had annual VOC rates of 2.7, compared with 4.0 among patients on the low dose of the drug. By comparison, VOC rates in SUSTAIN were 1.7 per year for the 5-mg/kg–dose group and 3.2 per year for the 2.5-mg/kg–dose group.

Overall, at least 60% of patients in the follow-up study had at least one hospitalization in the year after SUSTAIN. In the higher-dose group, the rates of hospitalization were similar in both SUSTAIN and SUCCESSOR – 53%. In the lower-dose group, hospitalization rates were 67% and 61% in SUCCESSOR and SUSTAIN, respectively.

“Among the previously treated patients with crizanlizumab, the total number of emergency department visits did seem to be higher in SUCCESSOR,” Dr. Shah said.

The study was limited by its retrospective nature and the fact that full data sets and follow-up were available on only a small number of patients, Dr. Shah said. “It was underpowered for a statistical analysis between groups,” he said. The goal was to determine the drug’s effect after treatment is discontinued, he said.

Dr. Shah reported a financial relationship with Novartis, which is developing crizanlizumab.

SOURCE: Shah N et al. FSCDR 2019, Abstract JSCDH-D-19-00031.

FORT LAUDERDALE, Fla. – A study of sickle cell patients at a clinic in the Bronx found that upwards of 75% of them get a prescription for hydroxyurea to improve hemoglobin levels, but that one-third have discontinued use for various reasons, according to results reported at the 13^th annual Foundation for Sickle Cell Disease Research symposium here.

“The results identify variability in reported side effects and reasons for discontinuation, and highlight the importance of clear communication between providers and patients to discuss the benefits and challenges of hydroxyurea,” said Caterina Minniti, MD, professor of clinical medicine and pediatrics at Einstein College of Medicine and director of the Sickle Cell Center for Adults at Montefiore Hospital, Bronx, N.Y. The study analyzed self-reporting surveys completed by 224 adult outpatients in the Montefiore sickle cell clinic, and then verified the data in the electronic medical record, Dr. Minniti said. She noted, “Our population is unique in the Bronx in that we have a high percentage of Hispanic patients.” They comprised 24.1% of the study population.

“We found that 77.2% of the patients have ever been prescribed hydroxyurea,” she said. “That was really great.” Also, 91% of those with severe genotypes of SCD had been prescribed the drug; 68% of them were still taking hydroxyurea at the time of the survey, she said. Among patients with the mild genotype, 42.1% had been prescribed hydroxyurea and half were still on it when they completed their surveys.

When the survey evaluated how long patients had been taking the drug, she said, “That’s where I start to get concerned.” About half – 48.6% – had taken the drug for one to five years, “which is a very short period of time,” Dr. Minniti said. Another 15% were on hydroxyurea for less than a year, 23% for 5 to 10 years and 19% for 10 years or more.

The study drilled down into reasons why patients discontinued the drug. Side effects were cited by 24.6% (n=15). They include fatigue, hair loss, and GI upset. Other reasons include perceived ineffectiveness (16.4%, n=10); physician direction (14.8%, n=9), and reproductive health and ulcer formation (each at 8.2%, n=5).

“Many patients perceive ineffectiveness of hydroxyurea in the short term, but the benefits of hydoxyurea stem from chronic use over the long term,” Dr. Minniti said. She noted that some patients discontinued the drug for legitimate medical indications, “such as pregnancy and breast feeding, but were not restarted afterward.”

Dr. Minniti disclosed relationships with Novartis, Global Blood Therapeutics, Teutona, Bluebird Bio, GBT and Bayer.

SOURCE: Minniti C, et al. Abstract no. JSCDH-D-19-00058. Foundation for Sickle Cell Disease Research Symposium; Fort Lauderdale, Fla.; June 9, 2019.

FORT LAUDERDALE, Fla. – A study of sickle cell patients at a clinic in the Bronx found that upwards of 75% of them get a prescription for hydroxyurea to improve hemoglobin levels, but that one-third have discontinued use for various reasons, according to results reported at the 13^th annual Foundation for Sickle Cell Disease Research symposium here.

“The results identify variability in reported side effects and reasons for discontinuation, and highlight the importance of clear communication between providers and patients to discuss the benefits and challenges of hydroxyurea,” said Caterina Minniti, MD, professor of clinical medicine and pediatrics at Einstein College of Medicine and director of the Sickle Cell Center for Adults at Montefiore Hospital, Bronx, N.Y. The study analyzed self-reporting surveys completed by 224 adult outpatients in the Montefiore sickle cell clinic, and then verified the data in the electronic medical record, Dr. Minniti said. She noted, “Our population is unique in the Bronx in that we have a high percentage of Hispanic patients.” They comprised 24.1% of the study population.

“We found that 77.2% of the patients have ever been prescribed hydroxyurea,” she said. “That was really great.” Also, 91% of those with severe genotypes of SCD had been prescribed the drug; 68% of them were still taking hydroxyurea at the time of the survey, she said. Among patients with the mild genotype, 42.1% had been prescribed hydroxyurea and half were still on it when they completed their surveys.

When the survey evaluated how long patients had been taking the drug, she said, “That’s where I start to get concerned.” About half – 48.6% – had taken the drug for one to five years, “which is a very short period of time,” Dr. Minniti said. Another 15% were on hydroxyurea for less than a year, 23% for 5 to 10 years and 19% for 10 years or more.

The study drilled down into reasons why patients discontinued the drug. Side effects were cited by 24.6% (n=15). They include fatigue, hair loss, and GI upset. Other reasons include perceived ineffectiveness (16.4%, n=10); physician direction (14.8%, n=9), and reproductive health and ulcer formation (each at 8.2%, n=5).

“Many patients perceive ineffectiveness of hydroxyurea in the short term, but the benefits of hydoxyurea stem from chronic use over the long term,” Dr. Minniti said. She noted that some patients discontinued the drug for legitimate medical indications, “such as pregnancy and breast feeding, but were not restarted afterward.”

Dr. Minniti disclosed relationships with Novartis, Global Blood Therapeutics, Teutona, Bluebird Bio, GBT and Bayer.

SOURCE: Minniti C, et al. Abstract no. JSCDH-D-19-00058. Foundation for Sickle Cell Disease Research Symposium; Fort Lauderdale, Fla.; June 9, 2019.

FORT LAUDERDALE, Fla. – A study of sickle cell patients at a clinic in the Bronx found that upwards of 75% of them get a prescription for hydroxyurea to improve hemoglobin levels, but that one-third have discontinued use for various reasons, according to results reported at the 13^th annual Foundation for Sickle Cell Disease Research symposium here.

“The results identify variability in reported side effects and reasons for discontinuation, and highlight the importance of clear communication between providers and patients to discuss the benefits and challenges of hydroxyurea,” said Caterina Minniti, MD, professor of clinical medicine and pediatrics at Einstein College of Medicine and director of the Sickle Cell Center for Adults at Montefiore Hospital, Bronx, N.Y. The study analyzed self-reporting surveys completed by 224 adult outpatients in the Montefiore sickle cell clinic, and then verified the data in the electronic medical record, Dr. Minniti said. She noted, “Our population is unique in the Bronx in that we have a high percentage of Hispanic patients.” They comprised 24.1% of the study population.

“We found that 77.2% of the patients have ever been prescribed hydroxyurea,” she said. “That was really great.” Also, 91% of those with severe genotypes of SCD had been prescribed the drug; 68% of them were still taking hydroxyurea at the time of the survey, she said. Among patients with the mild genotype, 42.1% had been prescribed hydroxyurea and half were still on it when they completed their surveys.

When the survey evaluated how long patients had been taking the drug, she said, “That’s where I start to get concerned.” About half – 48.6% – had taken the drug for one to five years, “which is a very short period of time,” Dr. Minniti said. Another 15% were on hydroxyurea for less than a year, 23% for 5 to 10 years and 19% for 10 years or more.

The study drilled down into reasons why patients discontinued the drug. Side effects were cited by 24.6% (n=15). They include fatigue, hair loss, and GI upset. Other reasons include perceived ineffectiveness (16.4%, n=10); physician direction (14.8%, n=9), and reproductive health and ulcer formation (each at 8.2%, n=5).

“Many patients perceive ineffectiveness of hydroxyurea in the short term, but the benefits of hydoxyurea stem from chronic use over the long term,” Dr. Minniti said. She noted that some patients discontinued the drug for legitimate medical indications, “such as pregnancy and breast feeding, but were not restarted afterward.”

Dr. Minniti disclosed relationships with Novartis, Global Blood Therapeutics, Teutona, Bluebird Bio, GBT and Bayer.

SOURCE: Minniti C, et al. Abstract no. JSCDH-D-19-00058. Foundation for Sickle Cell Disease Research Symposium; Fort Lauderdale, Fla.; June 9, 2019.

FORT LAUDERDALE, FLA. – Hip joint pain and deterioration can be a painful and disabling outcome for patients with sickle cell disease, but femoral head core decompression with the addition of bone marrow aspirate concentrate decreases their pain and may help avoid or delay hip replacement, according to results of a pilot study presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

Eric Fornari, MD, of the Children’s Hospital at Montefiore in Bronx, N.Y., reported on results of core decompression (CD) in 35 hips of 26 sickle cell patients; 17 underwent CD only and 18 had CD with injection of bone marrow aspirate concentrate (CD+BMAC). The average patient age was 24.3 years, with a range from 9.7-50.7 years.

“Compared to patients treated with CD alone, patients treated with CD+BMAC complained of significantly less pain and had significant improvement in their functional scores and patient-related outcomes at short-term follow-up,” Dr. Fornari said.

Among the CD+BMAC patients, pain scores declined two points on average, from 6 preoperatively to 4 postoperatively, he said. This was clinically significant, compared with the CD-only group, Dr. Fornari said.

Patients in the CD+BMAC group also reported consistently superior hip outcome and modified Harris hip scores. With either treatment, more than 90% of patients were pain-free and walked independently at their most recent follow-up, he said.

The objective of CD is to relieve pressure within the head of the femur, stimulate vascularity and target the avascular necrosis (AVN) lesion within the head that is visible on imaging. To get the bone marrow aspirate concentrate, Dr. Fornari extracts 120 cc of bone marrow from the iliac crest, then concentrates it to 12 cc. The same instrument is used to tap into the femoral head and inject the bone marrow aspirate concentrate. The study looked at clinical and radiographic outcomes of treated patients.

Average follow-up for the entire study population was 3.6 years, but that varied widely between the two groups (CD-only at almost 6 years, CD+BMAC at 1.4 years) because CD+BMAC has only been done for the last 3 years, Dr. Fornari said.

Progression to total hip arthroplasty (THA) was similar between both groups: 5 of 17 patients (29%) for CD-only vs. 4 of 18 patients (22%) for CD+BMAC (P = .711).

“When you look at progression, there were a number of hips that got CD or CD+BMAC and were better postoperatively; they went from a Ficat score of stage II to a stage I, or stage III to stage II,” he said.

X-rays were not always a reliable marker of outcome after either CD procedure, Dr. Fornari noted. “I’ve seen patients who’ve had terrible looking X-rays who have no pain, and patients who have totally normal X-rays that are completely debilitated,” he said. “We have to start asking ourselves, ‘What is the marker of success?’ because when we do this patients are feeling better.”

Multivariate analysis was used to identify factors predictive of progression to THA after the procedure, Dr. Fornari said. “Age of diagnosis, age of surgery, female gender, and lower hydroxyurea dose at surgery were predictive of advancing disease, whereas a higher dose of hydroxyurea was predictive against advancement,” he said.

The average age of patients who had no THA after either procedure was 21 years, compared with 33.9 years for those who had THA (P = .003). Average hydroxyurea dose at surgery was 24.7 mg/kg in the no-THA group vs. 12.5 mg/kg in those who had THA (P = .005).

Notably, there were no readmissions, fractures, deep vein thromboses, pulmonary embolisms or infarctions after CD, Dr. Fornari said. Transfusions were required in two CD-only and three CD+BMAC patients. Hospitalization rates for vaso-occlusive crisis were similar between groups (P = .103).

Dr. Fornari said the challenge is to identify suitable patients for these procedures. “These are complicated patients and you don’t want to put them through the process of having surgery, putting them on crutches and restricted weight bearing, if they’re not going to get better,” he said. “This procedure done minimally invasively is not the end all and be all, but we have to figure out who are the right patients for it. Patient selection is key.”

Finding those patients starts with a rigorous history and physical exam, he said. Physicians should have a “low threshold” for MRI in these patients because that will reveal findings, such as pre-collapse disease and characteristic of AVN lesions, that may appear normal on X-ray. Patient education is also important. “To think that an injection into the top of the hip is going to solve all their problems is a little naive, so you have to have an honest conversation with the patient,” he said.

Dr. Fornari reported having no financial disclosures.

SOURCE: Fornari ED et al. FSCDR 2019, Abstract JSCDH-D-19-00004.

FORT LAUDERDALE, FLA. – Hip joint pain and deterioration can be a painful and disabling outcome for patients with sickle cell disease, but femoral head core decompression with the addition of bone marrow aspirate concentrate decreases their pain and may help avoid or delay hip replacement, according to results of a pilot study presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

Eric Fornari, MD, of the Children’s Hospital at Montefiore in Bronx, N.Y., reported on results of core decompression (CD) in 35 hips of 26 sickle cell patients; 17 underwent CD only and 18 had CD with injection of bone marrow aspirate concentrate (CD+BMAC). The average patient age was 24.3 years, with a range from 9.7-50.7 years.

“Compared to patients treated with CD alone, patients treated with CD+BMAC complained of significantly less pain and had significant improvement in their functional scores and patient-related outcomes at short-term follow-up,” Dr. Fornari said.

Among the CD+BMAC patients, pain scores declined two points on average, from 6 preoperatively to 4 postoperatively, he said. This was clinically significant, compared with the CD-only group, Dr. Fornari said.

Patients in the CD+BMAC group also reported consistently superior hip outcome and modified Harris hip scores. With either treatment, more than 90% of patients were pain-free and walked independently at their most recent follow-up, he said.

The objective of CD is to relieve pressure within the head of the femur, stimulate vascularity and target the avascular necrosis (AVN) lesion within the head that is visible on imaging. To get the bone marrow aspirate concentrate, Dr. Fornari extracts 120 cc of bone marrow from the iliac crest, then concentrates it to 12 cc. The same instrument is used to tap into the femoral head and inject the bone marrow aspirate concentrate. The study looked at clinical and radiographic outcomes of treated patients.

Average follow-up for the entire study population was 3.6 years, but that varied widely between the two groups (CD-only at almost 6 years, CD+BMAC at 1.4 years) because CD+BMAC has only been done for the last 3 years, Dr. Fornari said.

Progression to total hip arthroplasty (THA) was similar between both groups: 5 of 17 patients (29%) for CD-only vs. 4 of 18 patients (22%) for CD+BMAC (P = .711).

“When you look at progression, there were a number of hips that got CD or CD+BMAC and were better postoperatively; they went from a Ficat score of stage II to a stage I, or stage III to stage II,” he said.

X-rays were not always a reliable marker of outcome after either CD procedure, Dr. Fornari noted. “I’ve seen patients who’ve had terrible looking X-rays who have no pain, and patients who have totally normal X-rays that are completely debilitated,” he said. “We have to start asking ourselves, ‘What is the marker of success?’ because when we do this patients are feeling better.”

Multivariate analysis was used to identify factors predictive of progression to THA after the procedure, Dr. Fornari said. “Age of diagnosis, age of surgery, female gender, and lower hydroxyurea dose at surgery were predictive of advancing disease, whereas a higher dose of hydroxyurea was predictive against advancement,” he said.

The average age of patients who had no THA after either procedure was 21 years, compared with 33.9 years for those who had THA (P = .003). Average hydroxyurea dose at surgery was 24.7 mg/kg in the no-THA group vs. 12.5 mg/kg in those who had THA (P = .005).

Notably, there were no readmissions, fractures, deep vein thromboses, pulmonary embolisms or infarctions after CD, Dr. Fornari said. Transfusions were required in two CD-only and three CD+BMAC patients. Hospitalization rates for vaso-occlusive crisis were similar between groups (P = .103).

Dr. Fornari said the challenge is to identify suitable patients for these procedures. “These are complicated patients and you don’t want to put them through the process of having surgery, putting them on crutches and restricted weight bearing, if they’re not going to get better,” he said. “This procedure done minimally invasively is not the end all and be all, but we have to figure out who are the right patients for it. Patient selection is key.”

Finding those patients starts with a rigorous history and physical exam, he said. Physicians should have a “low threshold” for MRI in these patients because that will reveal findings, such as pre-collapse disease and characteristic of AVN lesions, that may appear normal on X-ray. Patient education is also important. “To think that an injection into the top of the hip is going to solve all their problems is a little naive, so you have to have an honest conversation with the patient,” he said.

Dr. Fornari reported having no financial disclosures.

SOURCE: Fornari ED et al. FSCDR 2019, Abstract JSCDH-D-19-00004.

FORT LAUDERDALE, FLA. – Hip joint pain and deterioration can be a painful and disabling outcome for patients with sickle cell disease, but femoral head core decompression with the addition of bone marrow aspirate concentrate decreases their pain and may help avoid or delay hip replacement, according to results of a pilot study presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

Eric Fornari, MD, of the Children’s Hospital at Montefiore in Bronx, N.Y., reported on results of core decompression (CD) in 35 hips of 26 sickle cell patients; 17 underwent CD only and 18 had CD with injection of bone marrow aspirate concentrate (CD+BMAC). The average patient age was 24.3 years, with a range from 9.7-50.7 years.

“Compared to patients treated with CD alone, patients treated with CD+BMAC complained of significantly less pain and had significant improvement in their functional scores and patient-related outcomes at short-term follow-up,” Dr. Fornari said.

Among the CD+BMAC patients, pain scores declined two points on average, from 6 preoperatively to 4 postoperatively, he said. This was clinically significant, compared with the CD-only group, Dr. Fornari said.

Patients in the CD+BMAC group also reported consistently superior hip outcome and modified Harris hip scores. With either treatment, more than 90% of patients were pain-free and walked independently at their most recent follow-up, he said.

The objective of CD is to relieve pressure within the head of the femur, stimulate vascularity and target the avascular necrosis (AVN) lesion within the head that is visible on imaging. To get the bone marrow aspirate concentrate, Dr. Fornari extracts 120 cc of bone marrow from the iliac crest, then concentrates it to 12 cc. The same instrument is used to tap into the femoral head and inject the bone marrow aspirate concentrate. The study looked at clinical and radiographic outcomes of treated patients.

Average follow-up for the entire study population was 3.6 years, but that varied widely between the two groups (CD-only at almost 6 years, CD+BMAC at 1.4 years) because CD+BMAC has only been done for the last 3 years, Dr. Fornari said.

Progression to total hip arthroplasty (THA) was similar between both groups: 5 of 17 patients (29%) for CD-only vs. 4 of 18 patients (22%) for CD+BMAC (P = .711).

“When you look at progression, there were a number of hips that got CD or CD+BMAC and were better postoperatively; they went from a Ficat score of stage II to a stage I, or stage III to stage II,” he said.

X-rays were not always a reliable marker of outcome after either CD procedure, Dr. Fornari noted. “I’ve seen patients who’ve had terrible looking X-rays who have no pain, and patients who have totally normal X-rays that are completely debilitated,” he said. “We have to start asking ourselves, ‘What is the marker of success?’ because when we do this patients are feeling better.”

Multivariate analysis was used to identify factors predictive of progression to THA after the procedure, Dr. Fornari said. “Age of diagnosis, age of surgery, female gender, and lower hydroxyurea dose at surgery were predictive of advancing disease, whereas a higher dose of hydroxyurea was predictive against advancement,” he said.

The average age of patients who had no THA after either procedure was 21 years, compared with 33.9 years for those who had THA (P = .003). Average hydroxyurea dose at surgery was 24.7 mg/kg in the no-THA group vs. 12.5 mg/kg in those who had THA (P = .005).

Notably, there were no readmissions, fractures, deep vein thromboses, pulmonary embolisms or infarctions after CD, Dr. Fornari said. Transfusions were required in two CD-only and three CD+BMAC patients. Hospitalization rates for vaso-occlusive crisis were similar between groups (P = .103).

Dr. Fornari said the challenge is to identify suitable patients for these procedures. “These are complicated patients and you don’t want to put them through the process of having surgery, putting them on crutches and restricted weight bearing, if they’re not going to get better,” he said. “This procedure done minimally invasively is not the end all and be all, but we have to figure out who are the right patients for it. Patient selection is key.”

Finding those patients starts with a rigorous history and physical exam, he said. Physicians should have a “low threshold” for MRI in these patients because that will reveal findings, such as pre-collapse disease and characteristic of AVN lesions, that may appear normal on X-ray. Patient education is also important. “To think that an injection into the top of the hip is going to solve all their problems is a little naive, so you have to have an honest conversation with the patient,” he said.

Dr. Fornari reported having no financial disclosures.

SOURCE: Fornari ED et al. FSCDR 2019, Abstract JSCDH-D-19-00004.

FORT LAUDERDALE, FLA. – Orthopedic crises are common in patients with sickle cell disease, ranging from osteonecrosis to bone infarction, and physicians who manage these patients should know how to recognize these crises and not hesitate to consult an orthopedic surgeon early on, according to one expert at the annual meeting of the Foundation for Sickle Cell Disease Research.

Richard Mark Kirkner/MDedge News

“Sickle cell is a common entity in orthopedic surgery, so you shouldn’t hesitate in the hospital or outpatient settings to call for an orthopedic surgeon when you’re dealing with acute pain crises, medullary infarcts, and osteonecrosis,” said Mark W. Bridges, MD, an orthopedic surgeon with Orthopaedic Associates in Southern Florida.

Dr. Bridges noted that the femoral head is the most common location for osteonecrosis, one of the four major orthopedic manifestations of sickle cell disease that he reviewed. The others are septic arthritis, osteomyelitis, and bone infarction.

“Bone infarction is more common than osteomyelitis, and gadolinium-enhanced MRI can help to differentiate the two,” he said.

Osteonecrosis occurs when ischemic cells die, weakening the subchondral bone. Besides the femoral head, osteonecrosis commonly affects the humeral head of the shoulder and the femoral condyles of the knee. Dr. Bridges reviewed the five stages of the Ficat and Arlet classification of osteonecrosis:

• 0 – no pain, normal x-rays.
• I – pain, normal x-rays but abnormal MRI.
• II – pain, abnormal x-ray (sclerosis without collapse).
• III – pain (subchondral collapse without joint degeneration).
• IV – pain (arthritic changes with subchondral collapse).

For osteonecrosis of the shoulder, Dr. Bridges said four surgical options exist: core decompression for stages I and II; humeral head resurfacing for stages II and III; and hemiarthroplasty or total shoulder replacement for stages III and IV.

“No medical therapies are known to slow the progression,” he said.

Total joint replacement can be inevitable in these patients when total collapse of the joint occurs, but Dr. Bridges added a word of caution. “Overall when it comes down to replacing joints, there are more complications in patients that have [sickle cell disease],” he said. “Normally the complication rate is about 1%; that typically goes up to about 10% in SCD patients, but when you have a patient with end-stage disease – shoulder collapse or hip collapse – you have to do something.”

Septic arthritis is an infection within the joint space, most commonly the hip, and it affects 5% of children and 0.3% of adults with sickle cell disease (Clin Orthop Relat Res. 2010;468:1676-81).

“This is very similar to a vaso-occlusive crisis,” Dr. Bridges said.

MRI with gadolinium can help guide treatment, and blood cultures and joint aspiration can identify the infectious microbe. Staphylococcus aureus is the most common, Dr. Bridges said. Treatment consists of IV antibiotics, irrigation, and debridement.

Osteomyelitis is an infection within the bone with symptoms similar to those of septic arthritis, although osteomyelitis patients are typically sicker, he said. MRI with gadolinium is indicated in patients who don’t respond to IV fluid, oxygenation, and nonsteroidal anti-inflammatory drugs. “Try to treat them like they have vaso-occlusive crisis,” he said. Blood cultures usually suffice in these patients; bone aspiration is rarely needed, Dr. Bridges said.

The most common organisms are Staphylococcus aureus and Salmonella, and sickle cell disease patients can have infections in more than one location, Dr. Bridges noted.

“If IV antibiotics don’t work, then these patients need surgical debridement,” he added.

Adults are prone to a higher rate of complications than are children, including joint stiffness, osteonecrosis, pathologic fracture, and chronic osteomyelitis.

Ischemic marrow from vaso-occlusion can result in bone infarction. With its severe pain, swelling, erythema, and loss of motion, bone infarction can appear similar to osteomyelitis and septic arthritis, although a high-grade fever is uncommon in bone infarction. Unlike osteomyelitis, gadolinium on MRI does not enhance in bone infarction.

Treatment “consists of supportive management with pain medications, hydration, and antibiotics until osteomyelitis is ruled out,” Dr. Bridges said.

When a patient with one of these orthopedic conditions needs surgery, there are three considerations: preoperative transfusions to achieve hemoglobin level of 10 mg/dL for major procedures; no transfusions for arthroscopy and small closed reductions; and postoperative oxygenation and hydration to prevent a vaso-occlusive event and acute chest syndrome, he said.

Dr. Bridges reported having no conflicts of interest.

FORT LAUDERDALE, FLA. – Orthopedic crises are common in patients with sickle cell disease, ranging from osteonecrosis to bone infarction, and physicians who manage these patients should know how to recognize these crises and not hesitate to consult an orthopedic surgeon early on, according to one expert at the annual meeting of the Foundation for Sickle Cell Disease Research.

Richard Mark Kirkner/MDedge News

“Sickle cell is a common entity in orthopedic surgery, so you shouldn’t hesitate in the hospital or outpatient settings to call for an orthopedic surgeon when you’re dealing with acute pain crises, medullary infarcts, and osteonecrosis,” said Mark W. Bridges, MD, an orthopedic surgeon with Orthopaedic Associates in Southern Florida.

Dr. Bridges noted that the femoral head is the most common location for osteonecrosis, one of the four major orthopedic manifestations of sickle cell disease that he reviewed. The others are septic arthritis, osteomyelitis, and bone infarction.

“Bone infarction is more common than osteomyelitis, and gadolinium-enhanced MRI can help to differentiate the two,” he said.

Osteonecrosis occurs when ischemic cells die, weakening the subchondral bone. Besides the femoral head, osteonecrosis commonly affects the humeral head of the shoulder and the femoral condyles of the knee. Dr. Bridges reviewed the five stages of the Ficat and Arlet classification of osteonecrosis:

• 0 – no pain, normal x-rays.
• I – pain, normal x-rays but abnormal MRI.
• II – pain, abnormal x-ray (sclerosis without collapse).
• III – pain (subchondral collapse without joint degeneration).
• IV – pain (arthritic changes with subchondral collapse).

For osteonecrosis of the shoulder, Dr. Bridges said four surgical options exist: core decompression for stages I and II; humeral head resurfacing for stages II and III; and hemiarthroplasty or total shoulder replacement for stages III and IV.

“No medical therapies are known to slow the progression,” he said.

Total joint replacement can be inevitable in these patients when total collapse of the joint occurs, but Dr. Bridges added a word of caution. “Overall when it comes down to replacing joints, there are more complications in patients that have [sickle cell disease],” he said. “Normally the complication rate is about 1%; that typically goes up to about 10% in SCD patients, but when you have a patient with end-stage disease – shoulder collapse or hip collapse – you have to do something.”

Septic arthritis is an infection within the joint space, most commonly the hip, and it affects 5% of children and 0.3% of adults with sickle cell disease (Clin Orthop Relat Res. 2010;468:1676-81).

“This is very similar to a vaso-occlusive crisis,” Dr. Bridges said.

MRI with gadolinium can help guide treatment, and blood cultures and joint aspiration can identify the infectious microbe. Staphylococcus aureus is the most common, Dr. Bridges said. Treatment consists of IV antibiotics, irrigation, and debridement.

Osteomyelitis is an infection within the bone with symptoms similar to those of septic arthritis, although osteomyelitis patients are typically sicker, he said. MRI with gadolinium is indicated in patients who don’t respond to IV fluid, oxygenation, and nonsteroidal anti-inflammatory drugs. “Try to treat them like they have vaso-occlusive crisis,” he said. Blood cultures usually suffice in these patients; bone aspiration is rarely needed, Dr. Bridges said.

The most common organisms are Staphylococcus aureus and Salmonella, and sickle cell disease patients can have infections in more than one location, Dr. Bridges noted.

“If IV antibiotics don’t work, then these patients need surgical debridement,” he added.

Adults are prone to a higher rate of complications than are children, including joint stiffness, osteonecrosis, pathologic fracture, and chronic osteomyelitis.

Ischemic marrow from vaso-occlusion can result in bone infarction. With its severe pain, swelling, erythema, and loss of motion, bone infarction can appear similar to osteomyelitis and septic arthritis, although a high-grade fever is uncommon in bone infarction. Unlike osteomyelitis, gadolinium on MRI does not enhance in bone infarction.

Treatment “consists of supportive management with pain medications, hydration, and antibiotics until osteomyelitis is ruled out,” Dr. Bridges said.

When a patient with one of these orthopedic conditions needs surgery, there are three considerations: preoperative transfusions to achieve hemoglobin level of 10 mg/dL for major procedures; no transfusions for arthroscopy and small closed reductions; and postoperative oxygenation and hydration to prevent a vaso-occlusive event and acute chest syndrome, he said.

Dr. Bridges reported having no conflicts of interest.

FORT LAUDERDALE, FLA. – Orthopedic crises are common in patients with sickle cell disease, ranging from osteonecrosis to bone infarction, and physicians who manage these patients should know how to recognize these crises and not hesitate to consult an orthopedic surgeon early on, according to one expert at the annual meeting of the Foundation for Sickle Cell Disease Research.

Richard Mark Kirkner/MDedge News

“Sickle cell is a common entity in orthopedic surgery, so you shouldn’t hesitate in the hospital or outpatient settings to call for an orthopedic surgeon when you’re dealing with acute pain crises, medullary infarcts, and osteonecrosis,” said Mark W. Bridges, MD, an orthopedic surgeon with Orthopaedic Associates in Southern Florida.

Dr. Bridges noted that the femoral head is the most common location for osteonecrosis, one of the four major orthopedic manifestations of sickle cell disease that he reviewed. The others are septic arthritis, osteomyelitis, and bone infarction.

“Bone infarction is more common than osteomyelitis, and gadolinium-enhanced MRI can help to differentiate the two,” he said.

Osteonecrosis occurs when ischemic cells die, weakening the subchondral bone. Besides the femoral head, osteonecrosis commonly affects the humeral head of the shoulder and the femoral condyles of the knee. Dr. Bridges reviewed the five stages of the Ficat and Arlet classification of osteonecrosis:

• 0 – no pain, normal x-rays.
• I – pain, normal x-rays but abnormal MRI.
• II – pain, abnormal x-ray (sclerosis without collapse).
• III – pain (subchondral collapse without joint degeneration).
• IV – pain (arthritic changes with subchondral collapse).

For osteonecrosis of the shoulder, Dr. Bridges said four surgical options exist: core decompression for stages I and II; humeral head resurfacing for stages II and III; and hemiarthroplasty or total shoulder replacement for stages III and IV.

“No medical therapies are known to slow the progression,” he said.

Total joint replacement can be inevitable in these patients when total collapse of the joint occurs, but Dr. Bridges added a word of caution. “Overall when it comes down to replacing joints, there are more complications in patients that have [sickle cell disease],” he said. “Normally the complication rate is about 1%; that typically goes up to about 10% in SCD patients, but when you have a patient with end-stage disease – shoulder collapse or hip collapse – you have to do something.”

Septic arthritis is an infection within the joint space, most commonly the hip, and it affects 5% of children and 0.3% of adults with sickle cell disease (Clin Orthop Relat Res. 2010;468:1676-81).

“This is very similar to a vaso-occlusive crisis,” Dr. Bridges said.

MRI with gadolinium can help guide treatment, and blood cultures and joint aspiration can identify the infectious microbe. Staphylococcus aureus is the most common, Dr. Bridges said. Treatment consists of IV antibiotics, irrigation, and debridement.

Osteomyelitis is an infection within the bone with symptoms similar to those of septic arthritis, although osteomyelitis patients are typically sicker, he said. MRI with gadolinium is indicated in patients who don’t respond to IV fluid, oxygenation, and nonsteroidal anti-inflammatory drugs. “Try to treat them like they have vaso-occlusive crisis,” he said. Blood cultures usually suffice in these patients; bone aspiration is rarely needed, Dr. Bridges said.

The most common organisms are Staphylococcus aureus and Salmonella, and sickle cell disease patients can have infections in more than one location, Dr. Bridges noted.

“If IV antibiotics don’t work, then these patients need surgical debridement,” he added.

Adults are prone to a higher rate of complications than are children, including joint stiffness, osteonecrosis, pathologic fracture, and chronic osteomyelitis.

Ischemic marrow from vaso-occlusion can result in bone infarction. With its severe pain, swelling, erythema, and loss of motion, bone infarction can appear similar to osteomyelitis and septic arthritis, although a high-grade fever is uncommon in bone infarction. Unlike osteomyelitis, gadolinium on MRI does not enhance in bone infarction.

Treatment “consists of supportive management with pain medications, hydration, and antibiotics until osteomyelitis is ruled out,” Dr. Bridges said.

When a patient with one of these orthopedic conditions needs surgery, there are three considerations: preoperative transfusions to achieve hemoglobin level of 10 mg/dL for major procedures; no transfusions for arthroscopy and small closed reductions; and postoperative oxygenation and hydration to prevent a vaso-occlusive event and acute chest syndrome, he said.

Dr. Bridges reported having no conflicts of interest.

FORT LAUDERDALE, FLA. – When the Food and Drug Administration in 2017 approved L-glutamine (Endari) to treat the symptoms of sickle cell disease (SCD), it was the first new drug indicated for the condition in nearly two decades. But a small study of sickle cell patients in New York has found that patients are having difficulty obtaining the drug and sticking to the regimen.

bubaone/DigitalVision Vectors

“We found out that there are multiple barriers, mostly insurance related, and that after 10 months only one-fifth of the patients were still actively taking this medication,” said Ugochi Ogu, MD, assistant director of the Sickle Cell Center for Adults at Montefiore Medical Center in New York. She presented preliminary study results at the annual meeting of the Foundation for Sickle Cell Disease Research.

L-glutamine oral powder is taken twice a day to treat the symptoms of SCD. GoodRx reports that the average cash price for a 60-day supply of L-glutamine is $2,773.

The study followed 101 patients prescribed L-glutamine at the Montefiore Medical Center. When they returned to the clinic, patients were asked about barriers to obtaining the medication and adherence to the twice-a-day dosing. The center used a nearby local specialty pharmacy to fill the prescriptions.

The study also evaluated adherence by calculating the mean possession ratio (MPR) utilizing pharmacy records. The average age of the patient population was 36 years, and 56% were women.

It’s the first study of L-glutamine barriers and adherence in SCD patients in the real-world setting, Dr. Ogu said.

At the end of the 10-month study period, 21% of the patients were actively taking the medication, she said. “Forty-three percent had discontinued the medication, and 33% never filled the prescriptions; 4% had received but never started Endari,” Dr. Ogu said.

Of the patients who never filled the prescriptions, Dr. Ogu reported that 27% said their insurer denied prior authorization, 19% said their deductible was too high, and 16% cited other insurance issues.

“So we can see that insurance alone accounted for over 60% of why patients did not receive or could not start the medication,” she said.

Most patients – 94% – either had Medicare or Medicaid; the remainder had private insurance.

Among the 43% of all study patients who stopped taking the medication, reasons given include poor adherence (47%), side effects (9%), pregnancy and breast feeding (5%), and no perceived benefit (5%), Dr. Ogu said. At the outset, pharmacy records estimated adherence at 74% by using the average MPR, a rate similar to the phase 3 trial adherence rate of 77.4%.

Patient education is important to eliminate these barriers to treatment for SCD, Dr. Ogu said. “The patients need to understand why they’re taking whatever medication you prescribe. We need to educate them about the side effects, and we need to make them understand why it’s important to take certain medications or how they’re going to help them,” she said.

But even more important, she added, is a systems-based method to deal with insurance barriers. “If 62% of the patients did not get the medication due to insurance issues, I don’t think we’re doing a good job of making it accessible to them.”

Dr. Ogu reported a financial relationship with Vertex.

SOURCE: Ogu U et al. FSCDR 2019, Abstract JSCDH-D-19-00041.




 

FORT LAUDERDALE, FLA. – When the Food and Drug Administration in 2017 approved L-glutamine (Endari) to treat the symptoms of sickle cell disease (SCD), it was the first new drug indicated for the condition in nearly two decades. But a small study of sickle cell patients in New York has found that patients are having difficulty obtaining the drug and sticking to the regimen.

bubaone/DigitalVision Vectors

“We found out that there are multiple barriers, mostly insurance related, and that after 10 months only one-fifth of the patients were still actively taking this medication,” said Ugochi Ogu, MD, assistant director of the Sickle Cell Center for Adults at Montefiore Medical Center in New York. She presented preliminary study results at the annual meeting of the Foundation for Sickle Cell Disease Research.

L-glutamine oral powder is taken twice a day to treat the symptoms of SCD. GoodRx reports that the average cash price for a 60-day supply of L-glutamine is $2,773.

The study followed 101 patients prescribed L-glutamine at the Montefiore Medical Center. When they returned to the clinic, patients were asked about barriers to obtaining the medication and adherence to the twice-a-day dosing. The center used a nearby local specialty pharmacy to fill the prescriptions.

The study also evaluated adherence by calculating the mean possession ratio (MPR) utilizing pharmacy records. The average age of the patient population was 36 years, and 56% were women.

It’s the first study of L-glutamine barriers and adherence in SCD patients in the real-world setting, Dr. Ogu said.

At the end of the 10-month study period, 21% of the patients were actively taking the medication, she said. “Forty-three percent had discontinued the medication, and 33% never filled the prescriptions; 4% had received but never started Endari,” Dr. Ogu said.

Of the patients who never filled the prescriptions, Dr. Ogu reported that 27% said their insurer denied prior authorization, 19% said their deductible was too high, and 16% cited other insurance issues.

“So we can see that insurance alone accounted for over 60% of why patients did not receive or could not start the medication,” she said.

Most patients – 94% – either had Medicare or Medicaid; the remainder had private insurance.

Among the 43% of all study patients who stopped taking the medication, reasons given include poor adherence (47%), side effects (9%), pregnancy and breast feeding (5%), and no perceived benefit (5%), Dr. Ogu said. At the outset, pharmacy records estimated adherence at 74% by using the average MPR, a rate similar to the phase 3 trial adherence rate of 77.4%.

Patient education is important to eliminate these barriers to treatment for SCD, Dr. Ogu said. “The patients need to understand why they’re taking whatever medication you prescribe. We need to educate them about the side effects, and we need to make them understand why it’s important to take certain medications or how they’re going to help them,” she said.

But even more important, she added, is a systems-based method to deal with insurance barriers. “If 62% of the patients did not get the medication due to insurance issues, I don’t think we’re doing a good job of making it accessible to them.”

Dr. Ogu reported a financial relationship with Vertex.

SOURCE: Ogu U et al. FSCDR 2019, Abstract JSCDH-D-19-00041.




 

FORT LAUDERDALE, FLA. – When the Food and Drug Administration in 2017 approved L-glutamine (Endari) to treat the symptoms of sickle cell disease (SCD), it was the first new drug indicated for the condition in nearly two decades. But a small study of sickle cell patients in New York has found that patients are having difficulty obtaining the drug and sticking to the regimen.

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“We found out that there are multiple barriers, mostly insurance related, and that after 10 months only one-fifth of the patients were still actively taking this medication,” said Ugochi Ogu, MD, assistant director of the Sickle Cell Center for Adults at Montefiore Medical Center in New York. She presented preliminary study results at the annual meeting of the Foundation for Sickle Cell Disease Research.

L-glutamine oral powder is taken twice a day to treat the symptoms of SCD. GoodRx reports that the average cash price for a 60-day supply of L-glutamine is $2,773.

The study followed 101 patients prescribed L-glutamine at the Montefiore Medical Center. When they returned to the clinic, patients were asked about barriers to obtaining the medication and adherence to the twice-a-day dosing. The center used a nearby local specialty pharmacy to fill the prescriptions.

The study also evaluated adherence by calculating the mean possession ratio (MPR) utilizing pharmacy records. The average age of the patient population was 36 years, and 56% were women.

It’s the first study of L-glutamine barriers and adherence in SCD patients in the real-world setting, Dr. Ogu said.

At the end of the 10-month study period, 21% of the patients were actively taking the medication, she said. “Forty-three percent had discontinued the medication, and 33% never filled the prescriptions; 4% had received but never started Endari,” Dr. Ogu said.

Of the patients who never filled the prescriptions, Dr. Ogu reported that 27% said their insurer denied prior authorization, 19% said their deductible was too high, and 16% cited other insurance issues.

“So we can see that insurance alone accounted for over 60% of why patients did not receive or could not start the medication,” she said.

Most patients – 94% – either had Medicare or Medicaid; the remainder had private insurance.

Among the 43% of all study patients who stopped taking the medication, reasons given include poor adherence (47%), side effects (9%), pregnancy and breast feeding (5%), and no perceived benefit (5%), Dr. Ogu said. At the outset, pharmacy records estimated adherence at 74% by using the average MPR, a rate similar to the phase 3 trial adherence rate of 77.4%.

Patient education is important to eliminate these barriers to treatment for SCD, Dr. Ogu said. “The patients need to understand why they’re taking whatever medication you prescribe. We need to educate them about the side effects, and we need to make them understand why it’s important to take certain medications or how they’re going to help them,” she said.

But even more important, she added, is a systems-based method to deal with insurance barriers. “If 62% of the patients did not get the medication due to insurance issues, I don’t think we’re doing a good job of making it accessible to them.”

Dr. Ogu reported a financial relationship with Vertex.

SOURCE: Ogu U et al. FSCDR 2019, Abstract JSCDH-D-19-00041.




 

FORT LAUDERDALE, FLA. — A multicenter pilot study of a prophylactic regimen for both matched sibling donor and unrelated donor bone marrow transplantation in adults with severe sickle cell disease has found similar overall and event-free survival rates between the two approaches, exceeding 90% and 85%, respectively, at one year, according to preliminary results presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

The results have led to a Phase 2 single-arm, multicenter trial, known as STRIDE , to evaluate a reduced toxicity preparative regimen consisting of busulfan (13.2 mg/kg), fludarabine (175   mg/m ² ) and antithymocyte globulin (ATG, 6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis in adults with sickle cell disease (SCD), said Lakshmanan Krishnamurti, MD, of Children’s Healthcare of Atlanta/Emory University. “The data are similar with 91% overall survival and 86% event-free survival,” he said.

The pilot study, published recently ( Am J Hematol. 2019;94:446-54 ), indicated the effectiveness of non-myeloablative conditioning in SCD patients with matched-sibling bone marrow transplant (BMT), with a higher intensity regimen of busulfan/fludarabine/ATG effective in unrelated donor BMT for other conditions, Dr. Krishnamurti said.

The pilot study also found that three-year event-free survival (EFS) of 82%, and statistically significant improvements in pain and health-related quality of life.

STRIDE is the first comparative study of BMT vs. standard of care in severe SCD, Dr. Krishnamurti added. The primary endpoint is overall survival at two years after biologic assignment, with longer-term outcomes including survival at three to 10 years post-hematopoietic stem cell transplantation (HSCT), and impact of BMT on sickle-related events, organ function, health-related quality of life and chronic pain.  

The pilot study included 22 patients between the ages of 17 and 36 who had BMT at eight centers. Seventeen patients received marrow from a sibling-matched donor and five patients received marrow from an unrelated donor. 

Dr. Krishnamurti referenced a recent study out of France that showed chimerism levels after transplant may be a determining physiological factor for outcomes (Haematologica. doi:10.3324/haematol.2018.213207 ). “So if chimerism is stable, somewhere in the 25% to 50% or better range, and hemoglobin levels are improved, this decrease hemolysis,” he said. “This is very important in understanding how to manage these patients.”

That study showed that rates of chronic GVHD up to 10 years post-transplant have steadily improved over the past three decades in patients with SCD who’ve had BMT, Dr. Krishnamurti noted. “But chronic GVHD is higher in patients age 16 to 30 vs. patients 15 and younger,” he said, “so that’s the reason to consider transplantation sooner in patients who have a matched sibling donor.”

The French study shows that BMT with sibling-matched donors has excellent outcomes in young children, Dr. Krishnamurti said. “Outcomes for adults with transplantation is becoming similar to that in children,” he added. “Age is an important predictor of outcomes and the risk for progressive morbidity-impaired quality of life and risk of mortality still exists in adults with sickle cell disease.”

The bottom line, he said, is that patients and caregivers must be given the opportunity to consider transplantation as an option at younger ages.

Dr. Krishnamurti did not disclose any financial relationships.

SOURCE: Krishnamurti L et al. FSCDR 2019

FORT LAUDERDALE, FLA. — A multicenter pilot study of a prophylactic regimen for both matched sibling donor and unrelated donor bone marrow transplantation in adults with severe sickle cell disease has found similar overall and event-free survival rates between the two approaches, exceeding 90% and 85%, respectively, at one year, according to preliminary results presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

The results have led to a Phase 2 single-arm, multicenter trial, known as STRIDE , to evaluate a reduced toxicity preparative regimen consisting of busulfan (13.2 mg/kg), fludarabine (175   mg/m ² ) and antithymocyte globulin (ATG, 6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis in adults with sickle cell disease (SCD), said Lakshmanan Krishnamurti, MD, of Children’s Healthcare of Atlanta/Emory University. “The data are similar with 91% overall survival and 86% event-free survival,” he said.

The pilot study, published recently ( Am J Hematol. 2019;94:446-54 ), indicated the effectiveness of non-myeloablative conditioning in SCD patients with matched-sibling bone marrow transplant (BMT), with a higher intensity regimen of busulfan/fludarabine/ATG effective in unrelated donor BMT for other conditions, Dr. Krishnamurti said.

The pilot study also found that three-year event-free survival (EFS) of 82%, and statistically significant improvements in pain and health-related quality of life.

STRIDE is the first comparative study of BMT vs. standard of care in severe SCD, Dr. Krishnamurti added. The primary endpoint is overall survival at two years after biologic assignment, with longer-term outcomes including survival at three to 10 years post-hematopoietic stem cell transplantation (HSCT), and impact of BMT on sickle-related events, organ function, health-related quality of life and chronic pain.  

The pilot study included 22 patients between the ages of 17 and 36 who had BMT at eight centers. Seventeen patients received marrow from a sibling-matched donor and five patients received marrow from an unrelated donor. 

Dr. Krishnamurti referenced a recent study out of France that showed chimerism levels after transplant may be a determining physiological factor for outcomes (Haematologica. doi:10.3324/haematol.2018.213207 ). “So if chimerism is stable, somewhere in the 25% to 50% or better range, and hemoglobin levels are improved, this decrease hemolysis,” he said. “This is very important in understanding how to manage these patients.”

That study showed that rates of chronic GVHD up to 10 years post-transplant have steadily improved over the past three decades in patients with SCD who’ve had BMT, Dr. Krishnamurti noted. “But chronic GVHD is higher in patients age 16 to 30 vs. patients 15 and younger,” he said, “so that’s the reason to consider transplantation sooner in patients who have a matched sibling donor.”

The French study shows that BMT with sibling-matched donors has excellent outcomes in young children, Dr. Krishnamurti said. “Outcomes for adults with transplantation is becoming similar to that in children,” he added. “Age is an important predictor of outcomes and the risk for progressive morbidity-impaired quality of life and risk of mortality still exists in adults with sickle cell disease.”

The bottom line, he said, is that patients and caregivers must be given the opportunity to consider transplantation as an option at younger ages.

Dr. Krishnamurti did not disclose any financial relationships.

SOURCE: Krishnamurti L et al. FSCDR 2019

FORT LAUDERDALE, FLA. — A multicenter pilot study of a prophylactic regimen for both matched sibling donor and unrelated donor bone marrow transplantation in adults with severe sickle cell disease has found similar overall and event-free survival rates between the two approaches, exceeding 90% and 85%, respectively, at one year, according to preliminary results presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

The results have led to a Phase 2 single-arm, multicenter trial, known as STRIDE , to evaluate a reduced toxicity preparative regimen consisting of busulfan (13.2 mg/kg), fludarabine (175   mg/m ² ) and antithymocyte globulin (ATG, 6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis in adults with sickle cell disease (SCD), said Lakshmanan Krishnamurti, MD, of Children’s Healthcare of Atlanta/Emory University. “The data are similar with 91% overall survival and 86% event-free survival,” he said.

The pilot study, published recently ( Am J Hematol. 2019;94:446-54 ), indicated the effectiveness of non-myeloablative conditioning in SCD patients with matched-sibling bone marrow transplant (BMT), with a higher intensity regimen of busulfan/fludarabine/ATG effective in unrelated donor BMT for other conditions, Dr. Krishnamurti said.

The pilot study also found that three-year event-free survival (EFS) of 82%, and statistically significant improvements in pain and health-related quality of life.

STRIDE is the first comparative study of BMT vs. standard of care in severe SCD, Dr. Krishnamurti added. The primary endpoint is overall survival at two years after biologic assignment, with longer-term outcomes including survival at three to 10 years post-hematopoietic stem cell transplantation (HSCT), and impact of BMT on sickle-related events, organ function, health-related quality of life and chronic pain.  

The pilot study included 22 patients between the ages of 17 and 36 who had BMT at eight centers. Seventeen patients received marrow from a sibling-matched donor and five patients received marrow from an unrelated donor. 

Dr. Krishnamurti referenced a recent study out of France that showed chimerism levels after transplant may be a determining physiological factor for outcomes (Haematologica. doi:10.3324/haematol.2018.213207 ). “So if chimerism is stable, somewhere in the 25% to 50% or better range, and hemoglobin levels are improved, this decrease hemolysis,” he said. “This is very important in understanding how to manage these patients.”

That study showed that rates of chronic GVHD up to 10 years post-transplant have steadily improved over the past three decades in patients with SCD who’ve had BMT, Dr. Krishnamurti noted. “But chronic GVHD is higher in patients age 16 to 30 vs. patients 15 and younger,” he said, “so that’s the reason to consider transplantation sooner in patients who have a matched sibling donor.”

The French study shows that BMT with sibling-matched donors has excellent outcomes in young children, Dr. Krishnamurti said. “Outcomes for adults with transplantation is becoming similar to that in children,” he added. “Age is an important predictor of outcomes and the risk for progressive morbidity-impaired quality of life and risk of mortality still exists in adults with sickle cell disease.”

The bottom line, he said, is that patients and caregivers must be given the opportunity to consider transplantation as an option at younger ages.

Dr. Krishnamurti did not disclose any financial relationships.

SOURCE: Krishnamurti L et al. FSCDR 2019