COPENHAGEN – In a classic case of clinical sibling rivalry, results of the POLLUX trial support the benefits of adding daratumumab to lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma, echoing results reported a few days earlier by investigators in the twin (and archly named) CASTOR trial

Among 569 patients with relapsed/refractory multiple myeloma, the addition of the anti-CD38 monoclonal antibody daratumumab (Darzalex) to lenalidomide (Revlimid) and dexamethasone was associated with a 63% reduction in the risk of disease progress or death, compared with len-dex alone, reported Dr. Meletios A Dimopoulos of the National and Kapodistrian University of Athens.

With daratumumab and len-dex, “there is the highest-ever response rate seen in relapsed or refractory myeloma; 93% of the patients achieved at least a partial response, and more importantly, 43% of the patients achieved a complete response,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

“The addition of daratumumab to lenalidomide and dexamethasone induces deep and durable responses. Data indicate that we can achieve minimal residual disease negativity status in a significant number of patients,” he added.

The trial was halted on May 20, 2016, after a preplanned interim analysis showed a significant improvement in the primary endpoint of a progression-free survival, compared with len-dex alone.

Dizygotic twins

Like their mythologic namesakes, who were twin sons from different fathers, the CASTOR and POLLUX trials differed somewhat in the patient populations treated and in trial design. The CASTOR trial is looking at the addition of daratumumab to bortezomib (Velcade) and dexamethasone, and excludes patients resistant to bortezomib. The POLLUX trial includes bortezomib-resistant patients, but excludes lenalidomide-resistant patients.

In addition, in CASTOR, patients were treated with the assigned regimen for a specified number of courses, followed by daratumumab maintenance, whereas patients in both arms in POLLUX continued on their assigned therapy until disease progression or unacceptable toxicity occurred.

POLLUX was a multicenter, randomized, open-label phase III trial in patients with relapsed/refractory multiple myeloma following one or more prior lines of therapy. They were randomized on a 1:1 basis to either len-dex (283 patients) or len-dex plus intravenous daratumumab at a dose of 16 mg/kg once a week during treatment cycles 1 and 2, every 2 weeks during cycles 3-6, and once only on day 1 of subsequent cycles.

After a median follow-up of 13.5 months, the median progression-free survival for patients treated with len-dex alone was 18.4 months, but the median was not yet reached among patients treated with daratumumab. The difference translated into a hazard ratio for progression-free survival with daratumumab of 0.37 (P less than .0001).

In addition, the antibody was associated with a significantly better overall response rate (93% for daratumumab vs. 76% for len-dex only; P less than .0001), as well as better rates of complete responses (43% vs. 19%, respectively; P less than .0001), and very good partial responses or better (76% vs. 44%, P less than .0001).

The combination was generally well tolerated, with adverse events consistent with the known safety profile of len-dex. Infusion reactions with daratumumab were generally mild, and tended to occur during the first infusion, Dr. Dimopoulos said.

Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam (the Netherlands), who moderated the briefing, commented that the progression-free survival curves with daratumumab appeared to plateau, and asked whether any patients in the trial could be considered to have been “cured.”

Dr. Dimopoulos replied that “although we believe that in the relapsed setting of myeloma, it is unlikely to achieve the cure rate, we are optimistic that there will be a sizable number of patients that will remain without progression for many months. Already from single-agent daratumumab where this patient population is far more heavily pretreated, there are patients who are without progression for several years.”

Dr. Dimopoulos has previously disclosed honoraria from Janssen, maker of daratumumab. Dr. Hagenbeek disclosed serving on an advisory board for Takeda, maker of bortezomib.

COPENHAGEN – In a classic case of clinical sibling rivalry, results of the POLLUX trial support the benefits of adding daratumumab to lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma, echoing results reported a few days earlier by investigators in the twin (and archly named) CASTOR trial

Among 569 patients with relapsed/refractory multiple myeloma, the addition of the anti-CD38 monoclonal antibody daratumumab (Darzalex) to lenalidomide (Revlimid) and dexamethasone was associated with a 63% reduction in the risk of disease progress or death, compared with len-dex alone, reported Dr. Meletios A Dimopoulos of the National and Kapodistrian University of Athens.

With daratumumab and len-dex, “there is the highest-ever response rate seen in relapsed or refractory myeloma; 93% of the patients achieved at least a partial response, and more importantly, 43% of the patients achieved a complete response,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

“The addition of daratumumab to lenalidomide and dexamethasone induces deep and durable responses. Data indicate that we can achieve minimal residual disease negativity status in a significant number of patients,” he added.

The trial was halted on May 20, 2016, after a preplanned interim analysis showed a significant improvement in the primary endpoint of a progression-free survival, compared with len-dex alone.

Dizygotic twins

Like their mythologic namesakes, who were twin sons from different fathers, the CASTOR and POLLUX trials differed somewhat in the patient populations treated and in trial design. The CASTOR trial is looking at the addition of daratumumab to bortezomib (Velcade) and dexamethasone, and excludes patients resistant to bortezomib. The POLLUX trial includes bortezomib-resistant patients, but excludes lenalidomide-resistant patients.

In addition, in CASTOR, patients were treated with the assigned regimen for a specified number of courses, followed by daratumumab maintenance, whereas patients in both arms in POLLUX continued on their assigned therapy until disease progression or unacceptable toxicity occurred.

POLLUX was a multicenter, randomized, open-label phase III trial in patients with relapsed/refractory multiple myeloma following one or more prior lines of therapy. They were randomized on a 1:1 basis to either len-dex (283 patients) or len-dex plus intravenous daratumumab at a dose of 16 mg/kg once a week during treatment cycles 1 and 2, every 2 weeks during cycles 3-6, and once only on day 1 of subsequent cycles.

After a median follow-up of 13.5 months, the median progression-free survival for patients treated with len-dex alone was 18.4 months, but the median was not yet reached among patients treated with daratumumab. The difference translated into a hazard ratio for progression-free survival with daratumumab of 0.37 (P less than .0001).

In addition, the antibody was associated with a significantly better overall response rate (93% for daratumumab vs. 76% for len-dex only; P less than .0001), as well as better rates of complete responses (43% vs. 19%, respectively; P less than .0001), and very good partial responses or better (76% vs. 44%, P less than .0001).

The combination was generally well tolerated, with adverse events consistent with the known safety profile of len-dex. Infusion reactions with daratumumab were generally mild, and tended to occur during the first infusion, Dr. Dimopoulos said.

Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam (the Netherlands), who moderated the briefing, commented that the progression-free survival curves with daratumumab appeared to plateau, and asked whether any patients in the trial could be considered to have been “cured.”

Dr. Dimopoulos replied that “although we believe that in the relapsed setting of myeloma, it is unlikely to achieve the cure rate, we are optimistic that there will be a sizable number of patients that will remain without progression for many months. Already from single-agent daratumumab where this patient population is far more heavily pretreated, there are patients who are without progression for several years.”

Dr. Dimopoulos has previously disclosed honoraria from Janssen, maker of daratumumab. Dr. Hagenbeek disclosed serving on an advisory board for Takeda, maker of bortezomib.

COPENHAGEN – In a classic case of clinical sibling rivalry, results of the POLLUX trial support the benefits of adding daratumumab to lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma, echoing results reported a few days earlier by investigators in the twin (and archly named) CASTOR trial

Among 569 patients with relapsed/refractory multiple myeloma, the addition of the anti-CD38 monoclonal antibody daratumumab (Darzalex) to lenalidomide (Revlimid) and dexamethasone was associated with a 63% reduction in the risk of disease progress or death, compared with len-dex alone, reported Dr. Meletios A Dimopoulos of the National and Kapodistrian University of Athens.

With daratumumab and len-dex, “there is the highest-ever response rate seen in relapsed or refractory myeloma; 93% of the patients achieved at least a partial response, and more importantly, 43% of the patients achieved a complete response,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

“The addition of daratumumab to lenalidomide and dexamethasone induces deep and durable responses. Data indicate that we can achieve minimal residual disease negativity status in a significant number of patients,” he added.

The trial was halted on May 20, 2016, after a preplanned interim analysis showed a significant improvement in the primary endpoint of a progression-free survival, compared with len-dex alone.

Dizygotic twins

Like their mythologic namesakes, who were twin sons from different fathers, the CASTOR and POLLUX trials differed somewhat in the patient populations treated and in trial design. The CASTOR trial is looking at the addition of daratumumab to bortezomib (Velcade) and dexamethasone, and excludes patients resistant to bortezomib. The POLLUX trial includes bortezomib-resistant patients, but excludes lenalidomide-resistant patients.

In addition, in CASTOR, patients were treated with the assigned regimen for a specified number of courses, followed by daratumumab maintenance, whereas patients in both arms in POLLUX continued on their assigned therapy until disease progression or unacceptable toxicity occurred.

POLLUX was a multicenter, randomized, open-label phase III trial in patients with relapsed/refractory multiple myeloma following one or more prior lines of therapy. They were randomized on a 1:1 basis to either len-dex (283 patients) or len-dex plus intravenous daratumumab at a dose of 16 mg/kg once a week during treatment cycles 1 and 2, every 2 weeks during cycles 3-6, and once only on day 1 of subsequent cycles.

After a median follow-up of 13.5 months, the median progression-free survival for patients treated with len-dex alone was 18.4 months, but the median was not yet reached among patients treated with daratumumab. The difference translated into a hazard ratio for progression-free survival with daratumumab of 0.37 (P less than .0001).

In addition, the antibody was associated with a significantly better overall response rate (93% for daratumumab vs. 76% for len-dex only; P less than .0001), as well as better rates of complete responses (43% vs. 19%, respectively; P less than .0001), and very good partial responses or better (76% vs. 44%, P less than .0001).

The combination was generally well tolerated, with adverse events consistent with the known safety profile of len-dex. Infusion reactions with daratumumab were generally mild, and tended to occur during the first infusion, Dr. Dimopoulos said.

Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam (the Netherlands), who moderated the briefing, commented that the progression-free survival curves with daratumumab appeared to plateau, and asked whether any patients in the trial could be considered to have been “cured.”

Dr. Dimopoulos replied that “although we believe that in the relapsed setting of myeloma, it is unlikely to achieve the cure rate, we are optimistic that there will be a sizable number of patients that will remain without progression for many months. Already from single-agent daratumumab where this patient population is far more heavily pretreated, there are patients who are without progression for several years.”

Dr. Dimopoulos has previously disclosed honoraria from Janssen, maker of daratumumab. Dr. Hagenbeek disclosed serving on an advisory board for Takeda, maker of bortezomib.

Copenhagen – The monoclonal antibody blinatumomab nearly doubled overall survival compared with standard chemotherapy among patients with relapsed or refractory B-cell precursor leukemia negative for the Philadelphia chromosome, investigators reported.

Among 405 patients enrolled in the TOWER study, a multicenter, open-label phase III trial, median overall survival for patients treated with blinatumomab (Blincyto) was 7.7 months, compared with 4.0 months for patients treated with one of four standard chemotherapy regimens (P = .012) reported Dr. Max S. Topp of Universitätsklinikum in Würzburg, Germany.

“Blinatumomab is the first immunotherapy agent to demonstrate an overall survival benefit when compared to chemotherapy in patients relapsing with adult acute lymphoblastic leukemia. It increases almost twofold the overall survival when compared to standard care. This was consistent in all subgroups that we were looking at, regardless of age, prior salvage therapy, or patients relapsing after an allo-transplantation,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

The trial was halted early, after a preplanned interim analysis showed a clear survival benefit with blinatumomab.

Blinatumomab is a bispecific T-cell engager (BiTE) antibody designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. As previously reported, it has induced high complete remission rates in patients with relapsed or refractory acute lymphoblastic leukemia (ALL).

In May 2015, the Food and Drug Administration granted blinatumomab accelerated approval for the treatment of adult patients with relapsed/refractory Philadelphia chromosome–negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

In the TOWER trial, patients with relapsed/refractory BCP-ALL were randomly assigned on a 2:1 basis to receive either blinatumomab (271 patients) or standard chemotherapy (134), consisting of the investigator’s choice of one of four defined regimens (based on either anthracyclines, histone deacetylase inhibitors, high-dose methotrexate, or clofarabine).

The patients were further stratified by age, prior salvage therapy, and prior allogeneic stem cell transplant (alloSCT).

Patients assigned to receive blinatumomab received it in 6-week cycles consisting of continuous infusions of 9 mcg/day in week 1 of cycle 1, then 28 mcg/day for weeks 3-4, followed by 2 weeks off. Patients were pretreated with dexamethasone for prophylaxis against the cytokine release syndrome.

Patients whose disease was in remission following two induction cycles could be continued on therapy until relapse.

As noted, the trial was halted early, after 248 patients had died; the primary analysis had been planned to occur after 330 patients had died.

In addition to the superior survival rates, blinatumomab was associated with a higher rate of complete responses (39% vs. 19%, P less than .001) and combined complete responses, complete hematologic responses, and complete responses with incomplete recovery of counts (46% vs. 28%, P = .001).

In all, 19% of patients assigned to blinatumomab and 17% assigned to chemotherapy died on study. Grade 3 or greater adverse events included neutropenia (38% of patients and 58%, respectively), infections (34% and 52%), neurologic events (9% and 8%), and the cytokine release syndrome (5% vs. 0%).

Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who moderated the briefing, asked Dr. Topp whether there were plans to use blinatumomab earlier in the course of disease.

Dr. Topp agreed that it might be a valuable addition to upfront therapy, noting that blinatumomab has been shown in a small percentage of patients who are positive for minimal residual disease to convert to being negative for minimal residual disease, and that this conversion was associated with improved overall survival.

Copenhagen – The monoclonal antibody blinatumomab nearly doubled overall survival compared with standard chemotherapy among patients with relapsed or refractory B-cell precursor leukemia negative for the Philadelphia chromosome, investigators reported.

Among 405 patients enrolled in the TOWER study, a multicenter, open-label phase III trial, median overall survival for patients treated with blinatumomab (Blincyto) was 7.7 months, compared with 4.0 months for patients treated with one of four standard chemotherapy regimens (P = .012) reported Dr. Max S. Topp of Universitätsklinikum in Würzburg, Germany.

“Blinatumomab is the first immunotherapy agent to demonstrate an overall survival benefit when compared to chemotherapy in patients relapsing with adult acute lymphoblastic leukemia. It increases almost twofold the overall survival when compared to standard care. This was consistent in all subgroups that we were looking at, regardless of age, prior salvage therapy, or patients relapsing after an allo-transplantation,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

The trial was halted early, after a preplanned interim analysis showed a clear survival benefit with blinatumomab.

Blinatumomab is a bispecific T-cell engager (BiTE) antibody designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. As previously reported, it has induced high complete remission rates in patients with relapsed or refractory acute lymphoblastic leukemia (ALL).

In May 2015, the Food and Drug Administration granted blinatumomab accelerated approval for the treatment of adult patients with relapsed/refractory Philadelphia chromosome–negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

In the TOWER trial, patients with relapsed/refractory BCP-ALL were randomly assigned on a 2:1 basis to receive either blinatumomab (271 patients) or standard chemotherapy (134), consisting of the investigator’s choice of one of four defined regimens (based on either anthracyclines, histone deacetylase inhibitors, high-dose methotrexate, or clofarabine).

The patients were further stratified by age, prior salvage therapy, and prior allogeneic stem cell transplant (alloSCT).

Patients assigned to receive blinatumomab received it in 6-week cycles consisting of continuous infusions of 9 mcg/day in week 1 of cycle 1, then 28 mcg/day for weeks 3-4, followed by 2 weeks off. Patients were pretreated with dexamethasone for prophylaxis against the cytokine release syndrome.

Patients whose disease was in remission following two induction cycles could be continued on therapy until relapse.

As noted, the trial was halted early, after 248 patients had died; the primary analysis had been planned to occur after 330 patients had died.

In addition to the superior survival rates, blinatumomab was associated with a higher rate of complete responses (39% vs. 19%, P less than .001) and combined complete responses, complete hematologic responses, and complete responses with incomplete recovery of counts (46% vs. 28%, P = .001).

In all, 19% of patients assigned to blinatumomab and 17% assigned to chemotherapy died on study. Grade 3 or greater adverse events included neutropenia (38% of patients and 58%, respectively), infections (34% and 52%), neurologic events (9% and 8%), and the cytokine release syndrome (5% vs. 0%).

Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who moderated the briefing, asked Dr. Topp whether there were plans to use blinatumomab earlier in the course of disease.

Dr. Topp agreed that it might be a valuable addition to upfront therapy, noting that blinatumomab has been shown in a small percentage of patients who are positive for minimal residual disease to convert to being negative for minimal residual disease, and that this conversion was associated with improved overall survival.

Copenhagen – The monoclonal antibody blinatumomab nearly doubled overall survival compared with standard chemotherapy among patients with relapsed or refractory B-cell precursor leukemia negative for the Philadelphia chromosome, investigators reported.

Among 405 patients enrolled in the TOWER study, a multicenter, open-label phase III trial, median overall survival for patients treated with blinatumomab (Blincyto) was 7.7 months, compared with 4.0 months for patients treated with one of four standard chemotherapy regimens (P = .012) reported Dr. Max S. Topp of Universitätsklinikum in Würzburg, Germany.

“Blinatumomab is the first immunotherapy agent to demonstrate an overall survival benefit when compared to chemotherapy in patients relapsing with adult acute lymphoblastic leukemia. It increases almost twofold the overall survival when compared to standard care. This was consistent in all subgroups that we were looking at, regardless of age, prior salvage therapy, or patients relapsing after an allo-transplantation,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

The trial was halted early, after a preplanned interim analysis showed a clear survival benefit with blinatumomab.

Blinatumomab is a bispecific T-cell engager (BiTE) antibody designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. As previously reported, it has induced high complete remission rates in patients with relapsed or refractory acute lymphoblastic leukemia (ALL).

In May 2015, the Food and Drug Administration granted blinatumomab accelerated approval for the treatment of adult patients with relapsed/refractory Philadelphia chromosome–negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

In the TOWER trial, patients with relapsed/refractory BCP-ALL were randomly assigned on a 2:1 basis to receive either blinatumomab (271 patients) or standard chemotherapy (134), consisting of the investigator’s choice of one of four defined regimens (based on either anthracyclines, histone deacetylase inhibitors, high-dose methotrexate, or clofarabine).

The patients were further stratified by age, prior salvage therapy, and prior allogeneic stem cell transplant (alloSCT).

Patients assigned to receive blinatumomab received it in 6-week cycles consisting of continuous infusions of 9 mcg/day in week 1 of cycle 1, then 28 mcg/day for weeks 3-4, followed by 2 weeks off. Patients were pretreated with dexamethasone for prophylaxis against the cytokine release syndrome.

Patients whose disease was in remission following two induction cycles could be continued on therapy until relapse.

As noted, the trial was halted early, after 248 patients had died; the primary analysis had been planned to occur after 330 patients had died.

In addition to the superior survival rates, blinatumomab was associated with a higher rate of complete responses (39% vs. 19%, P less than .001) and combined complete responses, complete hematologic responses, and complete responses with incomplete recovery of counts (46% vs. 28%, P = .001).

In all, 19% of patients assigned to blinatumomab and 17% assigned to chemotherapy died on study. Grade 3 or greater adverse events included neutropenia (38% of patients and 58%, respectively), infections (34% and 52%), neurologic events (9% and 8%), and the cytokine release syndrome (5% vs. 0%).

Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who moderated the briefing, asked Dr. Topp whether there were plans to use blinatumomab earlier in the course of disease.

Dr. Topp agreed that it might be a valuable addition to upfront therapy, noting that blinatumomab has been shown in a small percentage of patients who are positive for minimal residual disease to convert to being negative for minimal residual disease, and that this conversion was associated with improved overall survival.

NATIONAL HARBOR, MD. – A subgroup analysis of 46 patients of African descent with active relapsing-remitting multiple sclerosis (RRMS) from the CARE-MS I and CARE-MS II trials has demonstrated the efficacy of alemtuzumab over 5 years.

The long-term results implicate alemtuzumab as a valuable treatment option for RRMS patients of African descent. These patients are at higher risk of more severe disease.

HUNG KUO CHUN/Thinkstock

“In patients of African descent, alemtuzumab had clinical and [magnetic resonance imaging] efficacy comparable with that observed in the overall CARE-MS study population. Efficacy was durable over 5 years, with the majority of patients not receiving alemtuzumab treatment after month 12,” Dr. Annette Okai of the Multiple Sclerosis Treatment Center of Dallas reported at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Patients of African descent have a heightened risk of MS that is more severe and more rapidly debilitating than that of white patients. As well, disease-modifying therapies may not be as effective in this group. To seek a better treatment option, Dr. Okai and colleagues performed a subgroup analysis involving the alemtuzumab treatment arm of the CARE I and II phase III randomized trials.

In CARE-MS I and II, a total of 811 patients received two annual intravenous injections of 12 mg alemtuzumab during the 2-year core phase of the trial and as-needed treatment during the extension phase from years 3 to 5. The trial cohort comprised 46 patients of African descent (80% from the United States, 76% female). Thirty-two of the 46 patients entered the extension phase.

Of the 32 patients, 17 (53%) did not receive retreatment beginning in year 2, and 28 (88%) did not receive another disease-modifying treatment. The efficacy of alemtuzumab in the overall CARE-MS cohort and in patients of African descent was durable over the full 5 years of the study. In those of African descent, the cumulative 0- to 5-year annualized relapse rate was 0.16. Sixty percent of the patients of African descent were relapse free in years 3-5.

Disease severity as measured by Expanded Disability Status Scale scores did not change appreciably over the 5 years (mean change, +0.52). No evidence of disease activity (NEDA) was observed in 33% of alemtuzumab patients in years 0-2, compared with 13% of those in the subcutaneous interferon beta-1a arm of CARE-MS I and II. Rates of NEDA in year 3, 4, and 5 were 45%, 42%, and 56%, respectively, and NEDA was achieved by 25% of the patients of African descent from years 3 to 5.

There were no serious infusion-associated reactions in the patients of African descent and the safety profile was similar to the overall cohort.

The efficacy and durability of alemtuzumab in the overall cohort generally, and in the patients of African descent more particularly, could reflect immunomodulation that is linked to lymphocyte repopulation, Dr. Okai suggested.

“Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in this high-risk population,” she concluded.

The studies were sponsored by Genzyme and Bayer Healthcare Pharmaceuticals. Dr. Okai disclosed receiving consulting fees from Genzyme, Novartis, Teva, Genentech, Biogen, and EMD Serono.

NATIONAL HARBOR, MD. – A subgroup analysis of 46 patients of African descent with active relapsing-remitting multiple sclerosis (RRMS) from the CARE-MS I and CARE-MS II trials has demonstrated the efficacy of alemtuzumab over 5 years.

The long-term results implicate alemtuzumab as a valuable treatment option for RRMS patients of African descent. These patients are at higher risk of more severe disease.

HUNG KUO CHUN/Thinkstock

“In patients of African descent, alemtuzumab had clinical and [magnetic resonance imaging] efficacy comparable with that observed in the overall CARE-MS study population. Efficacy was durable over 5 years, with the majority of patients not receiving alemtuzumab treatment after month 12,” Dr. Annette Okai of the Multiple Sclerosis Treatment Center of Dallas reported at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Patients of African descent have a heightened risk of MS that is more severe and more rapidly debilitating than that of white patients. As well, disease-modifying therapies may not be as effective in this group. To seek a better treatment option, Dr. Okai and colleagues performed a subgroup analysis involving the alemtuzumab treatment arm of the CARE I and II phase III randomized trials.

In CARE-MS I and II, a total of 811 patients received two annual intravenous injections of 12 mg alemtuzumab during the 2-year core phase of the trial and as-needed treatment during the extension phase from years 3 to 5. The trial cohort comprised 46 patients of African descent (80% from the United States, 76% female). Thirty-two of the 46 patients entered the extension phase.

Of the 32 patients, 17 (53%) did not receive retreatment beginning in year 2, and 28 (88%) did not receive another disease-modifying treatment. The efficacy of alemtuzumab in the overall CARE-MS cohort and in patients of African descent was durable over the full 5 years of the study. In those of African descent, the cumulative 0- to 5-year annualized relapse rate was 0.16. Sixty percent of the patients of African descent were relapse free in years 3-5.

Disease severity as measured by Expanded Disability Status Scale scores did not change appreciably over the 5 years (mean change, +0.52). No evidence of disease activity (NEDA) was observed in 33% of alemtuzumab patients in years 0-2, compared with 13% of those in the subcutaneous interferon beta-1a arm of CARE-MS I and II. Rates of NEDA in year 3, 4, and 5 were 45%, 42%, and 56%, respectively, and NEDA was achieved by 25% of the patients of African descent from years 3 to 5.

There were no serious infusion-associated reactions in the patients of African descent and the safety profile was similar to the overall cohort.

The efficacy and durability of alemtuzumab in the overall cohort generally, and in the patients of African descent more particularly, could reflect immunomodulation that is linked to lymphocyte repopulation, Dr. Okai suggested.

“Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in this high-risk population,” she concluded.

The studies were sponsored by Genzyme and Bayer Healthcare Pharmaceuticals. Dr. Okai disclosed receiving consulting fees from Genzyme, Novartis, Teva, Genentech, Biogen, and EMD Serono.

NATIONAL HARBOR, MD. – A subgroup analysis of 46 patients of African descent with active relapsing-remitting multiple sclerosis (RRMS) from the CARE-MS I and CARE-MS II trials has demonstrated the efficacy of alemtuzumab over 5 years.

The long-term results implicate alemtuzumab as a valuable treatment option for RRMS patients of African descent. These patients are at higher risk of more severe disease.

HUNG KUO CHUN/Thinkstock

“In patients of African descent, alemtuzumab had clinical and [magnetic resonance imaging] efficacy comparable with that observed in the overall CARE-MS study population. Efficacy was durable over 5 years, with the majority of patients not receiving alemtuzumab treatment after month 12,” Dr. Annette Okai of the Multiple Sclerosis Treatment Center of Dallas reported at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Patients of African descent have a heightened risk of MS that is more severe and more rapidly debilitating than that of white patients. As well, disease-modifying therapies may not be as effective in this group. To seek a better treatment option, Dr. Okai and colleagues performed a subgroup analysis involving the alemtuzumab treatment arm of the CARE I and II phase III randomized trials.

In CARE-MS I and II, a total of 811 patients received two annual intravenous injections of 12 mg alemtuzumab during the 2-year core phase of the trial and as-needed treatment during the extension phase from years 3 to 5. The trial cohort comprised 46 patients of African descent (80% from the United States, 76% female). Thirty-two of the 46 patients entered the extension phase.

Of the 32 patients, 17 (53%) did not receive retreatment beginning in year 2, and 28 (88%) did not receive another disease-modifying treatment. The efficacy of alemtuzumab in the overall CARE-MS cohort and in patients of African descent was durable over the full 5 years of the study. In those of African descent, the cumulative 0- to 5-year annualized relapse rate was 0.16. Sixty percent of the patients of African descent were relapse free in years 3-5.

Disease severity as measured by Expanded Disability Status Scale scores did not change appreciably over the 5 years (mean change, +0.52). No evidence of disease activity (NEDA) was observed in 33% of alemtuzumab patients in years 0-2, compared with 13% of those in the subcutaneous interferon beta-1a arm of CARE-MS I and II. Rates of NEDA in year 3, 4, and 5 were 45%, 42%, and 56%, respectively, and NEDA was achieved by 25% of the patients of African descent from years 3 to 5.

There were no serious infusion-associated reactions in the patients of African descent and the safety profile was similar to the overall cohort.

The efficacy and durability of alemtuzumab in the overall cohort generally, and in the patients of African descent more particularly, could reflect immunomodulation that is linked to lymphocyte repopulation, Dr. Okai suggested.

“Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in this high-risk population,” she concluded.

The studies were sponsored by Genzyme and Bayer Healthcare Pharmaceuticals. Dr. Okai disclosed receiving consulting fees from Genzyme, Novartis, Teva, Genentech, Biogen, and EMD Serono.

NATIONAL HARBOR, MD. – A pair of studies by the same research team has clarified how poor sleep worsens cognitive and physical function in people with multiple sclerosis (MS) and how poor sleep can be improved by exercise.

Whether the better sleep directly relates to the cognitive and physical improvements was not shown conclusively. However, a link between exercise and transient cognitive improvement has been demonstrated by others.

©Eraxion/ thinkstockphotos.com

“Exercise may be a nonpharmacological and an inexpensive method to address sleep symptoms,” said Catherine Siengsukon, Ph.D., of the University of Kansas Medical Center, Kansas City, at the annual meeting of the Consortium of Multiple Sclerosis Centers.

About half of all people with MS experience poor sleep that results from the disease itself, medications, anxiety/depression, or other causes. The fatigue and reduced physical and psychological function diminish the quality of life and can increase the risk of mortality. “But it is unknown if poor sleep quality may impact physical function in individuals with MS,” said Dr. Siengsukon.

In healthy individuals, cognitive aspects like attention, working and long-term memory, information processing, decision making, and problem solving can all be affected by poor sleep. “But which cognitive domains are associated with poor sleep quality in people with MS is unknown,” said Dr. Siengsukon.

In the first study, 40 people (36 females) with MS (mainly relapsing-remitting MS) were analyzed through a battery of established tests of sleep quality, cognitive function, physical function, depression, anxiety, and quality of life. The subjects had a disease duration of about 12 years. All were ambulatory without the need of assistance, and none had sleep apnea.

About 68% of the subjects were considered poor sleepers with the remainder being good sleepers. They were comparable in age, sex, type of MS, disease duration, and cognitive impairment.

Compared with good sleepers, poor sleepers were significantly impaired in visuospatial memory and questionnaire-assessed physical function, were more fatigued, were more prone to be anxious and depressed, and had a worse quality of life. Independent factors of poor sleep quality included state and trait anxiety (P = .003 and .02, respectively).

“Evidence demonstrates that sleep consolidates memory. Therefore, poor sleep may selectively impair memory while not impacting other cognitive domains,” said Dr. Siengsukon.

In the second study, the influence of supervised, moderate exercise and home exercise on sleep quality was assessed in 22 other MS patients. Most had relapsing-remitting MS. The inclusion and exclusion criteria were similar to those for the first study, with additional exclusion criteria concerning cardiovascular risk of exercise.

The supervised stretching and exercise program for 12 subjects was done at a social center and utilized recumbent exercise machines, with the home-based program for 10 subjects consisting of stretching and outdoor walking. Both exercise programs were done three times weekly for 12 weeks.

Both exercise programs were beneficial in improving sleep, with the moderate-intensity program being relatively more effective than home-based exercise in two measurement scales of sleep. The greater benefit of moderate exercise might reflect the mode of exercise, with subjects feeling safer and more relaxed using a recumbent exerciser, Dr. Siengsukon said. Offering the exercise in a social setting might have been another plus.

“The results suggest that moderate-intensity exercise may improve cardiovascular fitness in people with MS. While both groups experienced moderate to large effects on sleep quality, the mechanism for improvement in sleep quality remains to be determined, as the improvement was not related to change in cardiorespiratory fitness,” said Dr. Siengsukon.

A link between treadmill exercise and transient cognitive improvement has been reported.

The studies were supported by the National Institutes of Health and the National Multiple Sclerosis Society. Dr. Siengsukon disclosed grant support from the National Multiple Sclerosis Society.

NATIONAL HARBOR, MD. – A pair of studies by the same research team has clarified how poor sleep worsens cognitive and physical function in people with multiple sclerosis (MS) and how poor sleep can be improved by exercise.

Whether the better sleep directly relates to the cognitive and physical improvements was not shown conclusively. However, a link between exercise and transient cognitive improvement has been demonstrated by others.

©Eraxion/ thinkstockphotos.com

“Exercise may be a nonpharmacological and an inexpensive method to address sleep symptoms,” said Catherine Siengsukon, Ph.D., of the University of Kansas Medical Center, Kansas City, at the annual meeting of the Consortium of Multiple Sclerosis Centers.

About half of all people with MS experience poor sleep that results from the disease itself, medications, anxiety/depression, or other causes. The fatigue and reduced physical and psychological function diminish the quality of life and can increase the risk of mortality. “But it is unknown if poor sleep quality may impact physical function in individuals with MS,” said Dr. Siengsukon.

In healthy individuals, cognitive aspects like attention, working and long-term memory, information processing, decision making, and problem solving can all be affected by poor sleep. “But which cognitive domains are associated with poor sleep quality in people with MS is unknown,” said Dr. Siengsukon.

In the first study, 40 people (36 females) with MS (mainly relapsing-remitting MS) were analyzed through a battery of established tests of sleep quality, cognitive function, physical function, depression, anxiety, and quality of life. The subjects had a disease duration of about 12 years. All were ambulatory without the need of assistance, and none had sleep apnea.

About 68% of the subjects were considered poor sleepers with the remainder being good sleepers. They were comparable in age, sex, type of MS, disease duration, and cognitive impairment.

Compared with good sleepers, poor sleepers were significantly impaired in visuospatial memory and questionnaire-assessed physical function, were more fatigued, were more prone to be anxious and depressed, and had a worse quality of life. Independent factors of poor sleep quality included state and trait anxiety (P = .003 and .02, respectively).

“Evidence demonstrates that sleep consolidates memory. Therefore, poor sleep may selectively impair memory while not impacting other cognitive domains,” said Dr. Siengsukon.

In the second study, the influence of supervised, moderate exercise and home exercise on sleep quality was assessed in 22 other MS patients. Most had relapsing-remitting MS. The inclusion and exclusion criteria were similar to those for the first study, with additional exclusion criteria concerning cardiovascular risk of exercise.

The supervised stretching and exercise program for 12 subjects was done at a social center and utilized recumbent exercise machines, with the home-based program for 10 subjects consisting of stretching and outdoor walking. Both exercise programs were done three times weekly for 12 weeks.

Both exercise programs were beneficial in improving sleep, with the moderate-intensity program being relatively more effective than home-based exercise in two measurement scales of sleep. The greater benefit of moderate exercise might reflect the mode of exercise, with subjects feeling safer and more relaxed using a recumbent exerciser, Dr. Siengsukon said. Offering the exercise in a social setting might have been another plus.

“The results suggest that moderate-intensity exercise may improve cardiovascular fitness in people with MS. While both groups experienced moderate to large effects on sleep quality, the mechanism for improvement in sleep quality remains to be determined, as the improvement was not related to change in cardiorespiratory fitness,” said Dr. Siengsukon.

A link between treadmill exercise and transient cognitive improvement has been reported.

The studies were supported by the National Institutes of Health and the National Multiple Sclerosis Society. Dr. Siengsukon disclosed grant support from the National Multiple Sclerosis Society.

NATIONAL HARBOR, MD. – A pair of studies by the same research team has clarified how poor sleep worsens cognitive and physical function in people with multiple sclerosis (MS) and how poor sleep can be improved by exercise.

Whether the better sleep directly relates to the cognitive and physical improvements was not shown conclusively. However, a link between exercise and transient cognitive improvement has been demonstrated by others.

©Eraxion/ thinkstockphotos.com

“Exercise may be a nonpharmacological and an inexpensive method to address sleep symptoms,” said Catherine Siengsukon, Ph.D., of the University of Kansas Medical Center, Kansas City, at the annual meeting of the Consortium of Multiple Sclerosis Centers.

About half of all people with MS experience poor sleep that results from the disease itself, medications, anxiety/depression, or other causes. The fatigue and reduced physical and psychological function diminish the quality of life and can increase the risk of mortality. “But it is unknown if poor sleep quality may impact physical function in individuals with MS,” said Dr. Siengsukon.

In healthy individuals, cognitive aspects like attention, working and long-term memory, information processing, decision making, and problem solving can all be affected by poor sleep. “But which cognitive domains are associated with poor sleep quality in people with MS is unknown,” said Dr. Siengsukon.

In the first study, 40 people (36 females) with MS (mainly relapsing-remitting MS) were analyzed through a battery of established tests of sleep quality, cognitive function, physical function, depression, anxiety, and quality of life. The subjects had a disease duration of about 12 years. All were ambulatory without the need of assistance, and none had sleep apnea.

About 68% of the subjects were considered poor sleepers with the remainder being good sleepers. They were comparable in age, sex, type of MS, disease duration, and cognitive impairment.

Compared with good sleepers, poor sleepers were significantly impaired in visuospatial memory and questionnaire-assessed physical function, were more fatigued, were more prone to be anxious and depressed, and had a worse quality of life. Independent factors of poor sleep quality included state and trait anxiety (P = .003 and .02, respectively).

“Evidence demonstrates that sleep consolidates memory. Therefore, poor sleep may selectively impair memory while not impacting other cognitive domains,” said Dr. Siengsukon.

In the second study, the influence of supervised, moderate exercise and home exercise on sleep quality was assessed in 22 other MS patients. Most had relapsing-remitting MS. The inclusion and exclusion criteria were similar to those for the first study, with additional exclusion criteria concerning cardiovascular risk of exercise.

The supervised stretching and exercise program for 12 subjects was done at a social center and utilized recumbent exercise machines, with the home-based program for 10 subjects consisting of stretching and outdoor walking. Both exercise programs were done three times weekly for 12 weeks.

Both exercise programs were beneficial in improving sleep, with the moderate-intensity program being relatively more effective than home-based exercise in two measurement scales of sleep. The greater benefit of moderate exercise might reflect the mode of exercise, with subjects feeling safer and more relaxed using a recumbent exerciser, Dr. Siengsukon said. Offering the exercise in a social setting might have been another plus.

“The results suggest that moderate-intensity exercise may improve cardiovascular fitness in people with MS. While both groups experienced moderate to large effects on sleep quality, the mechanism for improvement in sleep quality remains to be determined, as the improvement was not related to change in cardiorespiratory fitness,” said Dr. Siengsukon.

A link between treadmill exercise and transient cognitive improvement has been reported.

The studies were supported by the National Institutes of Health and the National Multiple Sclerosis Society. Dr. Siengsukon disclosed grant support from the National Multiple Sclerosis Society.

SAN DIEGO – Tumor necrosis factor inhibitors improved the extraintestinal manifestations of inflammatory bowel disease (IBD) among more than half of affected patients, according to a national cohort study.

“The best response rates were for psoriasis, aphthous stomatitis, uveitis, and peripheral arthritis,” said Dr. Thomas Greuter of University Hospital in Zürich. Patients responded similarly whether they received oral infliximab or subcutaneous adalimumab or certolizumab, he noted.

IBD often is associated with debilitating disorders of the skin, joints, eyes, and hepatobiliary tract, but “due to the lack of randomized, controlled trials, the therapy of extraintestinal manifestations remains rather empirical,” Dr. Greuter said at the annual Digestive Disease Week.

To study the role of anti-TNF agents in treating these disorders, he and his associates analyzed data for 1,249 patients from the national Swiss IBD Cohort Study between 2006 and 2010. Patients were typically in their mid-30s and had lived with IBD for about 9 years, he said.

A total of 366 patients (29%) had at least one extraintestinal manifestation of IBD – most commonly peripheral arthritis (75%), followed by aphthous stomatitis (24%), and ankylosing spondylitis (22%). In all, 213 (58%) patients received at least one anti-TNF agent, and 40% received the prescription specifically for extraintestinal manifestations. Nearly two-thirds of the patients received infliximab, while 22% received adalimumab and 15% received certolizumab.

About 55% of patients improved on anti-TNF therapy over an average of 7 years of follow-up, Dr. Greuter and his associates reported. Among all three anti-TNF agents, response rates ranged from 100% for psoriasis, to 80% for erythema nodosum and stomatitis, to 73% for arthritis and uveitis, to 50% for pyoderma granulosum. Overall rates of improvement were slightly higher for infliximab than for the other two drugs, but “adalimumab and certolizumab were used mostly as a second or a third-line anti-TNF agent, and the response rate to a second or third-line treatment was lower than for the first one,” Dr. Greuter said. Some patients also received corticosteroids and immunomodulators, but excluding this subgroup had little effect on rates of response to anti-TNF therapy, he added.

Dr. Greuter also reported that 11 patients (about 5% of the cohort) developed 14 new extraintestinal manifestations after starting anti-TNF agents – usually peripheral arthritis, but also pyoderma granulosum, aphthous stomatitis, psoriasis, and uveitis. “We cannot say if this was primary, or a side effect of treatment,” he said. These disorders usually improved if patients stayed on their anti-TNF agent, he added.

About two-thirds of patients in the cohort were female, more than three-quarters had Crohn’s disease, 19% had ulcerative colitis, and 3% had indeterminate colitis, he noted.

A research grant from the Swiss National Science Foundation funded the study. Dr. Greuter had no disclosures.

SAN DIEGO – Tumor necrosis factor inhibitors improved the extraintestinal manifestations of inflammatory bowel disease (IBD) among more than half of affected patients, according to a national cohort study.

“The best response rates were for psoriasis, aphthous stomatitis, uveitis, and peripheral arthritis,” said Dr. Thomas Greuter of University Hospital in Zürich. Patients responded similarly whether they received oral infliximab or subcutaneous adalimumab or certolizumab, he noted.

IBD often is associated with debilitating disorders of the skin, joints, eyes, and hepatobiliary tract, but “due to the lack of randomized, controlled trials, the therapy of extraintestinal manifestations remains rather empirical,” Dr. Greuter said at the annual Digestive Disease Week.

To study the role of anti-TNF agents in treating these disorders, he and his associates analyzed data for 1,249 patients from the national Swiss IBD Cohort Study between 2006 and 2010. Patients were typically in their mid-30s and had lived with IBD for about 9 years, he said.

A total of 366 patients (29%) had at least one extraintestinal manifestation of IBD – most commonly peripheral arthritis (75%), followed by aphthous stomatitis (24%), and ankylosing spondylitis (22%). In all, 213 (58%) patients received at least one anti-TNF agent, and 40% received the prescription specifically for extraintestinal manifestations. Nearly two-thirds of the patients received infliximab, while 22% received adalimumab and 15% received certolizumab.

About 55% of patients improved on anti-TNF therapy over an average of 7 years of follow-up, Dr. Greuter and his associates reported. Among all three anti-TNF agents, response rates ranged from 100% for psoriasis, to 80% for erythema nodosum and stomatitis, to 73% for arthritis and uveitis, to 50% for pyoderma granulosum. Overall rates of improvement were slightly higher for infliximab than for the other two drugs, but “adalimumab and certolizumab were used mostly as a second or a third-line anti-TNF agent, and the response rate to a second or third-line treatment was lower than for the first one,” Dr. Greuter said. Some patients also received corticosteroids and immunomodulators, but excluding this subgroup had little effect on rates of response to anti-TNF therapy, he added.

Dr. Greuter also reported that 11 patients (about 5% of the cohort) developed 14 new extraintestinal manifestations after starting anti-TNF agents – usually peripheral arthritis, but also pyoderma granulosum, aphthous stomatitis, psoriasis, and uveitis. “We cannot say if this was primary, or a side effect of treatment,” he said. These disorders usually improved if patients stayed on their anti-TNF agent, he added.

About two-thirds of patients in the cohort were female, more than three-quarters had Crohn’s disease, 19% had ulcerative colitis, and 3% had indeterminate colitis, he noted.

A research grant from the Swiss National Science Foundation funded the study. Dr. Greuter had no disclosures.

SAN DIEGO – Tumor necrosis factor inhibitors improved the extraintestinal manifestations of inflammatory bowel disease (IBD) among more than half of affected patients, according to a national cohort study.

“The best response rates were for psoriasis, aphthous stomatitis, uveitis, and peripheral arthritis,” said Dr. Thomas Greuter of University Hospital in Zürich. Patients responded similarly whether they received oral infliximab or subcutaneous adalimumab or certolizumab, he noted.

IBD often is associated with debilitating disorders of the skin, joints, eyes, and hepatobiliary tract, but “due to the lack of randomized, controlled trials, the therapy of extraintestinal manifestations remains rather empirical,” Dr. Greuter said at the annual Digestive Disease Week.

To study the role of anti-TNF agents in treating these disorders, he and his associates analyzed data for 1,249 patients from the national Swiss IBD Cohort Study between 2006 and 2010. Patients were typically in their mid-30s and had lived with IBD for about 9 years, he said.

A total of 366 patients (29%) had at least one extraintestinal manifestation of IBD – most commonly peripheral arthritis (75%), followed by aphthous stomatitis (24%), and ankylosing spondylitis (22%). In all, 213 (58%) patients received at least one anti-TNF agent, and 40% received the prescription specifically for extraintestinal manifestations. Nearly two-thirds of the patients received infliximab, while 22% received adalimumab and 15% received certolizumab.

About 55% of patients improved on anti-TNF therapy over an average of 7 years of follow-up, Dr. Greuter and his associates reported. Among all three anti-TNF agents, response rates ranged from 100% for psoriasis, to 80% for erythema nodosum and stomatitis, to 73% for arthritis and uveitis, to 50% for pyoderma granulosum. Overall rates of improvement were slightly higher for infliximab than for the other two drugs, but “adalimumab and certolizumab were used mostly as a second or a third-line anti-TNF agent, and the response rate to a second or third-line treatment was lower than for the first one,” Dr. Greuter said. Some patients also received corticosteroids and immunomodulators, but excluding this subgroup had little effect on rates of response to anti-TNF therapy, he added.

Dr. Greuter also reported that 11 patients (about 5% of the cohort) developed 14 new extraintestinal manifestations after starting anti-TNF agents – usually peripheral arthritis, but also pyoderma granulosum, aphthous stomatitis, psoriasis, and uveitis. “We cannot say if this was primary, or a side effect of treatment,” he said. These disorders usually improved if patients stayed on their anti-TNF agent, he added.

About two-thirds of patients in the cohort were female, more than three-quarters had Crohn’s disease, 19% had ulcerative colitis, and 3% had indeterminate colitis, he noted.

A research grant from the Swiss National Science Foundation funded the study. Dr. Greuter had no disclosures.

Despite following guidelines aimed at reducing the likelihood of tuberculosis infection in patients with psoriasis treated with tumor necrosis factor antagonists, a French study has identified a number of active TB cases in this patient group.

The nationwide retrospective study identified 12 cases of tuberculosis in individuals with psoriasis during treatment with a TNF-antagonist between 2006 and 2014 – 9 men and 3 women, whose mean age was 49 years – according to Dr. E. Guinard of the dermatology service, CHU Toulouse Larrey at Paul Sabatier University, Toulouse, France, and associates (J Eur Acad Dermatol Venereol. 2016 Jun 3. doi: 10.1111/jdv.13633).

The investigators identified the cases from a national pharmacosurveillance database and by contacting members of the psoriasis research group in France’s national dermatology society and the national college of French dermatology professors.

Before starting anti-TNF therapy, all 12 patients had been screened for latent TB based on French guidelines: three patients were tested with the tuberculosis skin test alone, six were tested with QuantiFERON-TB Gold test, and three patients had both the skin test and QuantiFERON-TB. Each had a pretreatment chest x-ray.

Based on this testing, three were diagnosed with latent TB and received chemoprophylaxis; the other nine patients tested negative.

Information on TB risk factors was not available for all 12 cases, but three people had had contact with someone with TB during treatment. Three of the individuals had traveled to or were born in areas where TB was endemic, and one patient had had a case of TB in the family in the year before starting anti-TNF therapy. Nine patients had a known history of BCG vaccination, the investigators said.

The time between starting anti-TNF therapy and the appearance of TB symptoms ranged from 2 to 176 weeks (mean, 23 weeks), and diagnosis was based on clinical signs – such as fever, night sweats, and cough – and on imaging and laboratory investigations. Most (10) of the cases were extrapulmonary presentations, and two were pleuropulmonary. When diagnosed with tuberculosis, seven of the patients were being treated with infliximab, four were being treated with adalimumab, and one was being treated with certolizumab. All stopped anti-TNF therapy once they were diagnosed with tuberculosis.

Dr. Guinard and associates noted that the low sensitivity of Mycobacterium tuberculosis diagnostic tests was “a striking feature” of these cases. Only one-third of the patients showed a positive direct Ziehl-Neelsen stain for acid-fast bacilli and half had a positive culture.

“According to this study and published experience, in a patient with suggestive symptoms, a negative Mycobacterium tuberculosis test should not delay the decision to initiate anti-tuberculosis treatment,” they wrote. “This is particularly important considering the high mortality of tuberculosis in patients treated with TNF antagonists,” which ranges from 6%-17%, they added.

Two of the twelve patients – aged 77 and 32 years – died of disseminated tuberculosis disease during treatment for TB.

“This is the largest study of tuberculosis in psoriasis patients treated with TNF antagonists,” according to the authors.

No conflicts of interest were declared, and the study had no funding source.

Despite following guidelines aimed at reducing the likelihood of tuberculosis infection in patients with psoriasis treated with tumor necrosis factor antagonists, a French study has identified a number of active TB cases in this patient group.

The nationwide retrospective study identified 12 cases of tuberculosis in individuals with psoriasis during treatment with a TNF-antagonist between 2006 and 2014 – 9 men and 3 women, whose mean age was 49 years – according to Dr. E. Guinard of the dermatology service, CHU Toulouse Larrey at Paul Sabatier University, Toulouse, France, and associates (J Eur Acad Dermatol Venereol. 2016 Jun 3. doi: 10.1111/jdv.13633).

The investigators identified the cases from a national pharmacosurveillance database and by contacting members of the psoriasis research group in France’s national dermatology society and the national college of French dermatology professors.

Before starting anti-TNF therapy, all 12 patients had been screened for latent TB based on French guidelines: three patients were tested with the tuberculosis skin test alone, six were tested with QuantiFERON-TB Gold test, and three patients had both the skin test and QuantiFERON-TB. Each had a pretreatment chest x-ray.

Based on this testing, three were diagnosed with latent TB and received chemoprophylaxis; the other nine patients tested negative.

Information on TB risk factors was not available for all 12 cases, but three people had had contact with someone with TB during treatment. Three of the individuals had traveled to or were born in areas where TB was endemic, and one patient had had a case of TB in the family in the year before starting anti-TNF therapy. Nine patients had a known history of BCG vaccination, the investigators said.

The time between starting anti-TNF therapy and the appearance of TB symptoms ranged from 2 to 176 weeks (mean, 23 weeks), and diagnosis was based on clinical signs – such as fever, night sweats, and cough – and on imaging and laboratory investigations. Most (10) of the cases were extrapulmonary presentations, and two were pleuropulmonary. When diagnosed with tuberculosis, seven of the patients were being treated with infliximab, four were being treated with adalimumab, and one was being treated with certolizumab. All stopped anti-TNF therapy once they were diagnosed with tuberculosis.

Dr. Guinard and associates noted that the low sensitivity of Mycobacterium tuberculosis diagnostic tests was “a striking feature” of these cases. Only one-third of the patients showed a positive direct Ziehl-Neelsen stain for acid-fast bacilli and half had a positive culture.

“According to this study and published experience, in a patient with suggestive symptoms, a negative Mycobacterium tuberculosis test should not delay the decision to initiate anti-tuberculosis treatment,” they wrote. “This is particularly important considering the high mortality of tuberculosis in patients treated with TNF antagonists,” which ranges from 6%-17%, they added.

Two of the twelve patients – aged 77 and 32 years – died of disseminated tuberculosis disease during treatment for TB.

“This is the largest study of tuberculosis in psoriasis patients treated with TNF antagonists,” according to the authors.

No conflicts of interest were declared, and the study had no funding source.

Despite following guidelines aimed at reducing the likelihood of tuberculosis infection in patients with psoriasis treated with tumor necrosis factor antagonists, a French study has identified a number of active TB cases in this patient group.

The nationwide retrospective study identified 12 cases of tuberculosis in individuals with psoriasis during treatment with a TNF-antagonist between 2006 and 2014 – 9 men and 3 women, whose mean age was 49 years – according to Dr. E. Guinard of the dermatology service, CHU Toulouse Larrey at Paul Sabatier University, Toulouse, France, and associates (J Eur Acad Dermatol Venereol. 2016 Jun 3. doi: 10.1111/jdv.13633).

The investigators identified the cases from a national pharmacosurveillance database and by contacting members of the psoriasis research group in France’s national dermatology society and the national college of French dermatology professors.

Before starting anti-TNF therapy, all 12 patients had been screened for latent TB based on French guidelines: three patients were tested with the tuberculosis skin test alone, six were tested with QuantiFERON-TB Gold test, and three patients had both the skin test and QuantiFERON-TB. Each had a pretreatment chest x-ray.

Based on this testing, three were diagnosed with latent TB and received chemoprophylaxis; the other nine patients tested negative.

Information on TB risk factors was not available for all 12 cases, but three people had had contact with someone with TB during treatment. Three of the individuals had traveled to or were born in areas where TB was endemic, and one patient had had a case of TB in the family in the year before starting anti-TNF therapy. Nine patients had a known history of BCG vaccination, the investigators said.

The time between starting anti-TNF therapy and the appearance of TB symptoms ranged from 2 to 176 weeks (mean, 23 weeks), and diagnosis was based on clinical signs – such as fever, night sweats, and cough – and on imaging and laboratory investigations. Most (10) of the cases were extrapulmonary presentations, and two were pleuropulmonary. When diagnosed with tuberculosis, seven of the patients were being treated with infliximab, four were being treated with adalimumab, and one was being treated with certolizumab. All stopped anti-TNF therapy once they were diagnosed with tuberculosis.

Dr. Guinard and associates noted that the low sensitivity of Mycobacterium tuberculosis diagnostic tests was “a striking feature” of these cases. Only one-third of the patients showed a positive direct Ziehl-Neelsen stain for acid-fast bacilli and half had a positive culture.

“According to this study and published experience, in a patient with suggestive symptoms, a negative Mycobacterium tuberculosis test should not delay the decision to initiate anti-tuberculosis treatment,” they wrote. “This is particularly important considering the high mortality of tuberculosis in patients treated with TNF antagonists,” which ranges from 6%-17%, they added.

Two of the twelve patients – aged 77 and 32 years – died of disseminated tuberculosis disease during treatment for TB.

“This is the largest study of tuberculosis in psoriasis patients treated with TNF antagonists,” according to the authors.

No conflicts of interest were declared, and the study had no funding source.

People with osteoarthritis who go on to have a total or partial knee replacement do not appear to have an increased risk of all-cause mortality, but the jury is still out on whether they gain any improvement, a study showed.

In their research published in the Annals of the Rheumatic Diseases [2016 May 17. doi: 10.1136/annrheumdis-2016-209167], Dr. Devyani Misra of Boston University and colleagues noted that knee replacement (KR) was thought to decrease long-term mortality risk because of the relief from pain and improvement in function that typically comes with surgery. However, studies on the topic had been conflicting, largely because of the challenges associated with studying mortality with KR surgery in observational settings.

©Nandyphotos/Thinkstock

In the current study the research team sought to evaluate the relation of KR to the risk of all-cause mortality among subjects with knee OA, while at the same time giving particular attention to “potential sources of confounding bias that may account for [the] effect of KR on mortality.”

Using patient data from the U.K. primary care electronic database THIN, the investigators compared the risk of mortality among 14,042 subjects who had OA, were aged 50-89 years old, and had had or had not had KR.

They discovered a strong protective effect of KR on all-cause long-term mortality risk, particularly among the adults over 63 years of age.

For example, people who had undergone KR had a 28% lower risk of mortality than did non-KR subjects (hazard ratio, 0.72; 95% confidence interval, 0.66-0.78).

In the overall propensity score–matched study sample, crude mortality per 1,000 person-years (total person-years) for the KR and non-KR cohorts were 19 (61,015) and 25 (58,294), respectively.

However, despite their best efforts, the researchers said the results showed evidence of residual confounding.

“For example, the observation of improved survival immediately after KR, despite the expectation of potential short-term increased postoperative mortality risk supports the presence of residual confounding,” they wrote.

Another finding suggestive of confounding was that the protective effect was seen only in older patients (over 63) when the authors stratified study participants by age.

“While it is possible that survival benefit seen in older patients with KR is a true effect because it is in this group that greater physical activity is particularly important to survival, more likely it is a result of residual confounding because subject selection is rigorous in this age group due to vulnerability,” the authors wrote.

They concluded that knee replacement “did not appear to be associated with an increased risk of all-cause mortality.”

“While we cannot rule out that KR may potentially reduce the risk of mortality over the long term, the true extent of that potential benefit is difficult to discern due to confounding by indication in observational studies using administrative data or electronic health records,” they added.

This study was funded by the Arthritis Foundation Postdoctoral Fellowship Award, the ACR Rheumatology Research Foundation Investigator Award, and a Boston University scholarship grant.

People with osteoarthritis who go on to have a total or partial knee replacement do not appear to have an increased risk of all-cause mortality, but the jury is still out on whether they gain any improvement, a study showed.

In their research published in the Annals of the Rheumatic Diseases [2016 May 17. doi: 10.1136/annrheumdis-2016-209167], Dr. Devyani Misra of Boston University and colleagues noted that knee replacement (KR) was thought to decrease long-term mortality risk because of the relief from pain and improvement in function that typically comes with surgery. However, studies on the topic had been conflicting, largely because of the challenges associated with studying mortality with KR surgery in observational settings.

©Nandyphotos/Thinkstock

In the current study the research team sought to evaluate the relation of KR to the risk of all-cause mortality among subjects with knee OA, while at the same time giving particular attention to “potential sources of confounding bias that may account for [the] effect of KR on mortality.”

Using patient data from the U.K. primary care electronic database THIN, the investigators compared the risk of mortality among 14,042 subjects who had OA, were aged 50-89 years old, and had had or had not had KR.

They discovered a strong protective effect of KR on all-cause long-term mortality risk, particularly among the adults over 63 years of age.

For example, people who had undergone KR had a 28% lower risk of mortality than did non-KR subjects (hazard ratio, 0.72; 95% confidence interval, 0.66-0.78).

In the overall propensity score–matched study sample, crude mortality per 1,000 person-years (total person-years) for the KR and non-KR cohorts were 19 (61,015) and 25 (58,294), respectively.

However, despite their best efforts, the researchers said the results showed evidence of residual confounding.

“For example, the observation of improved survival immediately after KR, despite the expectation of potential short-term increased postoperative mortality risk supports the presence of residual confounding,” they wrote.

Another finding suggestive of confounding was that the protective effect was seen only in older patients (over 63) when the authors stratified study participants by age.

“While it is possible that survival benefit seen in older patients with KR is a true effect because it is in this group that greater physical activity is particularly important to survival, more likely it is a result of residual confounding because subject selection is rigorous in this age group due to vulnerability,” the authors wrote.

They concluded that knee replacement “did not appear to be associated with an increased risk of all-cause mortality.”

“While we cannot rule out that KR may potentially reduce the risk of mortality over the long term, the true extent of that potential benefit is difficult to discern due to confounding by indication in observational studies using administrative data or electronic health records,” they added.

This study was funded by the Arthritis Foundation Postdoctoral Fellowship Award, the ACR Rheumatology Research Foundation Investigator Award, and a Boston University scholarship grant.

People with osteoarthritis who go on to have a total or partial knee replacement do not appear to have an increased risk of all-cause mortality, but the jury is still out on whether they gain any improvement, a study showed.

In their research published in the Annals of the Rheumatic Diseases [2016 May 17. doi: 10.1136/annrheumdis-2016-209167], Dr. Devyani Misra of Boston University and colleagues noted that knee replacement (KR) was thought to decrease long-term mortality risk because of the relief from pain and improvement in function that typically comes with surgery. However, studies on the topic had been conflicting, largely because of the challenges associated with studying mortality with KR surgery in observational settings.

©Nandyphotos/Thinkstock

In the current study the research team sought to evaluate the relation of KR to the risk of all-cause mortality among subjects with knee OA, while at the same time giving particular attention to “potential sources of confounding bias that may account for [the] effect of KR on mortality.”

Using patient data from the U.K. primary care electronic database THIN, the investigators compared the risk of mortality among 14,042 subjects who had OA, were aged 50-89 years old, and had had or had not had KR.

They discovered a strong protective effect of KR on all-cause long-term mortality risk, particularly among the adults over 63 years of age.

For example, people who had undergone KR had a 28% lower risk of mortality than did non-KR subjects (hazard ratio, 0.72; 95% confidence interval, 0.66-0.78).

In the overall propensity score–matched study sample, crude mortality per 1,000 person-years (total person-years) for the KR and non-KR cohorts were 19 (61,015) and 25 (58,294), respectively.

However, despite their best efforts, the researchers said the results showed evidence of residual confounding.

“For example, the observation of improved survival immediately after KR, despite the expectation of potential short-term increased postoperative mortality risk supports the presence of residual confounding,” they wrote.

Another finding suggestive of confounding was that the protective effect was seen only in older patients (over 63) when the authors stratified study participants by age.

“While it is possible that survival benefit seen in older patients with KR is a true effect because it is in this group that greater physical activity is particularly important to survival, more likely it is a result of residual confounding because subject selection is rigorous in this age group due to vulnerability,” the authors wrote.

They concluded that knee replacement “did not appear to be associated with an increased risk of all-cause mortality.”

“While we cannot rule out that KR may potentially reduce the risk of mortality over the long term, the true extent of that potential benefit is difficult to discern due to confounding by indication in observational studies using administrative data or electronic health records,” they added.

This study was funded by the Arthritis Foundation Postdoctoral Fellowship Award, the ACR Rheumatology Research Foundation Investigator Award, and a Boston University scholarship grant.

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

[email protected]

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

[email protected]

The Food and Drug Administration has revised warnings on certain medications for type 2 diabetes mellitus based on recent reports of kidney injury. The warning labels on canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) now include recommendations on ways to minimize the risk and more information on kidney injury.

“From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use,” the FDA statement said.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA went on to note: “Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs). Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter. If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”

[email protected]

SAN DIEGO – Despite an increase in women entering the gastroenterology field, a new study finds that they are severely underrepresented in academia as fellowship program directors and division chiefs.

In addition, most female program directors have lower academic ranks than did their male counterparts.

“A lack of female leadership can detract future women from entering the field,” said study lead author Dr. Sonali Paul, a gastroenterologist and research fellow in medicine at Massachusetts General Hospital in Boston. “Further research is needed to understand these barriers, whether they’re due to personal choice or more systemic issues. Understanding the challenges women face in academic promotions will allow for policy changes.”

According to statistics quoted in the study, women made up more than a third of gastroenterology fellowship positions and 18% of the academic workforce in 2013. At the same time, more than half of medical graduates are women.

“The role of women in GI is important, especially given that studies have shown that women prefer female endoscopists,” Dr. Paul said. And women make up significant portions of the patient load in GI clinical practices, she said.

But it hasn’t been clear if the increase in fellowship positions has corresponded to a higher number of women in positions of academic leadership.

To better understand the situation, Dr. Paul and her associates analyzed the gender and academic rank of GI fellowship program directors and division chiefs in 2015. The researchers analyzed websites and social media to gather the data and also made direct contacts, Dr. Paul said.

At 165 academic GI programs, 85% of these positions were held by men. Of program directors, 81% were male; 89% of division chiefs were male.

Of the men who hold these positions, half were program directors and half were division chiefs. Among women, however, 67% were program directors and 33% were division chiefs.

There was also a disparity in terms of academic experience. Female division chiefs were less likely to be professors (46%), compared with male division chiefs (82%).

Why the disparity? One possible explanation is a “leaky pipeline,” Dr. Paul said. This refers to the fact that women leave academic medicine at higher rates than men do.

Family obligations are one explanation, she said, “but I don’t think that explains everything in the process. A lot of women have felt that promotion was of no benefit to them and that there was a lack of encouragement.”

Dr. Paul notes that the study has limitations. It’s cross sectional, and misclassification errors are possible.

During a discussion period, a questioner noted that it takes time for an academic physician to move up: “Shouldn’t we look at the fraction of graduates in 1996 who were female and now are professors? It’s unusual for someone at less than a professor rank to be division chief, as compared with program director.” Dr. Paul agreed that this would be a good avenue of research.

In addition, she said, “it will be important to examine if these gender disparities are unique to gastroenterology or if they extend into other specialties that are more female dominant, such as rheumatology or geriatrics.”

SAN DIEGO – Despite an increase in women entering the gastroenterology field, a new study finds that they are severely underrepresented in academia as fellowship program directors and division chiefs.

In addition, most female program directors have lower academic ranks than did their male counterparts.

“A lack of female leadership can detract future women from entering the field,” said study lead author Dr. Sonali Paul, a gastroenterologist and research fellow in medicine at Massachusetts General Hospital in Boston. “Further research is needed to understand these barriers, whether they’re due to personal choice or more systemic issues. Understanding the challenges women face in academic promotions will allow for policy changes.”

According to statistics quoted in the study, women made up more than a third of gastroenterology fellowship positions and 18% of the academic workforce in 2013. At the same time, more than half of medical graduates are women.

“The role of women in GI is important, especially given that studies have shown that women prefer female endoscopists,” Dr. Paul said. And women make up significant portions of the patient load in GI clinical practices, she said.

But it hasn’t been clear if the increase in fellowship positions has corresponded to a higher number of women in positions of academic leadership.

To better understand the situation, Dr. Paul and her associates analyzed the gender and academic rank of GI fellowship program directors and division chiefs in 2015. The researchers analyzed websites and social media to gather the data and also made direct contacts, Dr. Paul said.

At 165 academic GI programs, 85% of these positions were held by men. Of program directors, 81% were male; 89% of division chiefs were male.

Of the men who hold these positions, half were program directors and half were division chiefs. Among women, however, 67% were program directors and 33% were division chiefs.

There was also a disparity in terms of academic experience. Female division chiefs were less likely to be professors (46%), compared with male division chiefs (82%).

Why the disparity? One possible explanation is a “leaky pipeline,” Dr. Paul said. This refers to the fact that women leave academic medicine at higher rates than men do.

Family obligations are one explanation, she said, “but I don’t think that explains everything in the process. A lot of women have felt that promotion was of no benefit to them and that there was a lack of encouragement.”

Dr. Paul notes that the study has limitations. It’s cross sectional, and misclassification errors are possible.

During a discussion period, a questioner noted that it takes time for an academic physician to move up: “Shouldn’t we look at the fraction of graduates in 1996 who were female and now are professors? It’s unusual for someone at less than a professor rank to be division chief, as compared with program director.” Dr. Paul agreed that this would be a good avenue of research.

In addition, she said, “it will be important to examine if these gender disparities are unique to gastroenterology or if they extend into other specialties that are more female dominant, such as rheumatology or geriatrics.”

SAN DIEGO – Despite an increase in women entering the gastroenterology field, a new study finds that they are severely underrepresented in academia as fellowship program directors and division chiefs.

In addition, most female program directors have lower academic ranks than did their male counterparts.

“A lack of female leadership can detract future women from entering the field,” said study lead author Dr. Sonali Paul, a gastroenterologist and research fellow in medicine at Massachusetts General Hospital in Boston. “Further research is needed to understand these barriers, whether they’re due to personal choice or more systemic issues. Understanding the challenges women face in academic promotions will allow for policy changes.”

According to statistics quoted in the study, women made up more than a third of gastroenterology fellowship positions and 18% of the academic workforce in 2013. At the same time, more than half of medical graduates are women.

“The role of women in GI is important, especially given that studies have shown that women prefer female endoscopists,” Dr. Paul said. And women make up significant portions of the patient load in GI clinical practices, she said.

But it hasn’t been clear if the increase in fellowship positions has corresponded to a higher number of women in positions of academic leadership.

To better understand the situation, Dr. Paul and her associates analyzed the gender and academic rank of GI fellowship program directors and division chiefs in 2015. The researchers analyzed websites and social media to gather the data and also made direct contacts, Dr. Paul said.

At 165 academic GI programs, 85% of these positions were held by men. Of program directors, 81% were male; 89% of division chiefs were male.

Of the men who hold these positions, half were program directors and half were division chiefs. Among women, however, 67% were program directors and 33% were division chiefs.

There was also a disparity in terms of academic experience. Female division chiefs were less likely to be professors (46%), compared with male division chiefs (82%).

Why the disparity? One possible explanation is a “leaky pipeline,” Dr. Paul said. This refers to the fact that women leave academic medicine at higher rates than men do.

Family obligations are one explanation, she said, “but I don’t think that explains everything in the process. A lot of women have felt that promotion was of no benefit to them and that there was a lack of encouragement.”

Dr. Paul notes that the study has limitations. It’s cross sectional, and misclassification errors are possible.

During a discussion period, a questioner noted that it takes time for an academic physician to move up: “Shouldn’t we look at the fraction of graduates in 1996 who were female and now are professors? It’s unusual for someone at less than a professor rank to be division chief, as compared with program director.” Dr. Paul agreed that this would be a good avenue of research.

In addition, she said, “it will be important to examine if these gender disparities are unique to gastroenterology or if they extend into other specialties that are more female dominant, such as rheumatology or geriatrics.”