Pharmacology

Rituximab was greeted with high hopes as a treatment for the fatigue and dry eyes of primary Sjögren syndrome (pSS), a chronic autoimmune disorder. Typically, patients with fatigue or arthralgia are treated with hydroxychloroquine, and those with systemic involvement are treated with corticosteroids, methotrexate, or immunosuppressants. But recent research has been pointing toward B-cell depletion as a treatment, and the most widely studied target is the CD20 antigen.

In open-label studies, rituximab, an anti-CD20 antibody, had a good safety profile, induced rapid B-cell depletion in blood and salivary glands, and “seemed beneficial” in early active pSS and in pSS with active extraglandular involvement, say researchers who conducted the subsequent Tolerance and Efficacy of Rituximab in Primary Sjögren’s Syndrome (TEARS) trial.

Two small trials suggested an effect on fatigue and improvements in dryness symptoms. Those early promising findings led the TEARS trial researchers to conduct the multicenter (14 university hospitals in France), randomized, placebo-controlled trial to evaluate the efficacy and safety of rituximab in pSS. In the study, 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analog scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS were given rituximab 1 g at weeks 0 and 2 or placebo. The primary endpoint was improvement of at least 30 mm in 2 of 4 VASs by week 24.

Rituximab did not entirely fulfill its promise: It did not significantly increase the proportion of patients’ achieving the primary endpoint. However, it showed clinically significant improvements at week 6 (P = .036), suggesting transient efficacy of the study regimen that was not maintained throughout the 24-week period, the researchers say. Further, fatigue, the symptom that causes the most disability in patients with pSS, responded best—and quickly—to rituximab therapy. The VAS dryness score also improved, although by < 30 mm. Mean salivary flow rate was not improved.

Due to limitations of the study,  the researchers say they can’t recommend rituximab for patients with recent-onset or systemic pSS. But that doesn’t mean there couldn’t be better results. First, it would help to determine the best outcome measure for assessing treatment efficacy in pSS, which at the moment, they say, is “debatable.” They note that clinical trials of potentially disease-modifying treatments in pSS have used various outcome measures. For this study, they chose a large effect—improvement of at least 30 mm in at least 2 of 4 VAS scores evaluating different disease domains—which may have been insensitive to clinically important changes in symptoms.

They also point out that the best interval for assessing treatment efficacy in pSS is unclear. All previous studies on the biology of pSS evaluated the primary outcome between weeks 10 and 24; none of the studies suggested differences in treatment effects over time. For this study, the researchers chose 24 weeks, an interval that seemed consistent, they say, with the kinetics of effects of rituximab as established in patients with rheumatoid arthritis.

Finally, the study patients had low disease activity at baseline. The researchers say they cannot exclude a better effect of the treatment in more active pSS.

Thus, although rituximab didn’t produce sustained or substantial symptom relief, hope should not be abandoned—it still could prove its worth.

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

Rituximab was greeted with high hopes as a treatment for the fatigue and dry eyes of primary Sjögren syndrome (pSS), a chronic autoimmune disorder. Typically, patients with fatigue or arthralgia are treated with hydroxychloroquine, and those with systemic involvement are treated with corticosteroids, methotrexate, or immunosuppressants. But recent research has been pointing toward B-cell depletion as a treatment, and the most widely studied target is the CD20 antigen.

In open-label studies, rituximab, an anti-CD20 antibody, had a good safety profile, induced rapid B-cell depletion in blood and salivary glands, and “seemed beneficial” in early active pSS and in pSS with active extraglandular involvement, say researchers who conducted the subsequent Tolerance and Efficacy of Rituximab in Primary Sjögren’s Syndrome (TEARS) trial.

Two small trials suggested an effect on fatigue and improvements in dryness symptoms. Those early promising findings led the TEARS trial researchers to conduct the multicenter (14 university hospitals in France), randomized, placebo-controlled trial to evaluate the efficacy and safety of rituximab in pSS. In the study, 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analog scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS were given rituximab 1 g at weeks 0 and 2 or placebo. The primary endpoint was improvement of at least 30 mm in 2 of 4 VASs by week 24.

Rituximab did not entirely fulfill its promise: It did not significantly increase the proportion of patients’ achieving the primary endpoint. However, it showed clinically significant improvements at week 6 (P = .036), suggesting transient efficacy of the study regimen that was not maintained throughout the 24-week period, the researchers say. Further, fatigue, the symptom that causes the most disability in patients with pSS, responded best—and quickly—to rituximab therapy. The VAS dryness score also improved, although by < 30 mm. Mean salivary flow rate was not improved.

Due to limitations of the study,  the researchers say they can’t recommend rituximab for patients with recent-onset or systemic pSS. But that doesn’t mean there couldn’t be better results. First, it would help to determine the best outcome measure for assessing treatment efficacy in pSS, which at the moment, they say, is “debatable.” They note that clinical trials of potentially disease-modifying treatments in pSS have used various outcome measures. For this study, they chose a large effect—improvement of at least 30 mm in at least 2 of 4 VAS scores evaluating different disease domains—which may have been insensitive to clinically important changes in symptoms.

They also point out that the best interval for assessing treatment efficacy in pSS is unclear. All previous studies on the biology of pSS evaluated the primary outcome between weeks 10 and 24; none of the studies suggested differences in treatment effects over time. For this study, the researchers chose 24 weeks, an interval that seemed consistent, they say, with the kinetics of effects of rituximab as established in patients with rheumatoid arthritis.

Finally, the study patients had low disease activity at baseline. The researchers say they cannot exclude a better effect of the treatment in more active pSS.

Thus, although rituximab didn’t produce sustained or substantial symptom relief, hope should not be abandoned—it still could prove its worth.

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

Rituximab was greeted with high hopes as a treatment for the fatigue and dry eyes of primary Sjögren syndrome (pSS), a chronic autoimmune disorder. Typically, patients with fatigue or arthralgia are treated with hydroxychloroquine, and those with systemic involvement are treated with corticosteroids, methotrexate, or immunosuppressants. But recent research has been pointing toward B-cell depletion as a treatment, and the most widely studied target is the CD20 antigen.

In open-label studies, rituximab, an anti-CD20 antibody, had a good safety profile, induced rapid B-cell depletion in blood and salivary glands, and “seemed beneficial” in early active pSS and in pSS with active extraglandular involvement, say researchers who conducted the subsequent Tolerance and Efficacy of Rituximab in Primary Sjögren’s Syndrome (TEARS) trial.

Two small trials suggested an effect on fatigue and improvements in dryness symptoms. Those early promising findings led the TEARS trial researchers to conduct the multicenter (14 university hospitals in France), randomized, placebo-controlled trial to evaluate the efficacy and safety of rituximab in pSS. In the study, 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analog scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS were given rituximab 1 g at weeks 0 and 2 or placebo. The primary endpoint was improvement of at least 30 mm in 2 of 4 VASs by week 24.

Rituximab did not entirely fulfill its promise: It did not significantly increase the proportion of patients’ achieving the primary endpoint. However, it showed clinically significant improvements at week 6 (P = .036), suggesting transient efficacy of the study regimen that was not maintained throughout the 24-week period, the researchers say. Further, fatigue, the symptom that causes the most disability in patients with pSS, responded best—and quickly—to rituximab therapy. The VAS dryness score also improved, although by < 30 mm. Mean salivary flow rate was not improved.

Due to limitations of the study,  the researchers say they can’t recommend rituximab for patients with recent-onset or systemic pSS. But that doesn’t mean there couldn’t be better results. First, it would help to determine the best outcome measure for assessing treatment efficacy in pSS, which at the moment, they say, is “debatable.” They note that clinical trials of potentially disease-modifying treatments in pSS have used various outcome measures. For this study, they chose a large effect—improvement of at least 30 mm in at least 2 of 4 VAS scores evaluating different disease domains—which may have been insensitive to clinically important changes in symptoms.

They also point out that the best interval for assessing treatment efficacy in pSS is unclear. All previous studies on the biology of pSS evaluated the primary outcome between weeks 10 and 24; none of the studies suggested differences in treatment effects over time. For this study, the researchers chose 24 weeks, an interval that seemed consistent, they say, with the kinetics of effects of rituximab as established in patients with rheumatoid arthritis.

Finally, the study patients had low disease activity at baseline. The researchers say they cannot exclude a better effect of the treatment in more active pSS.

Thus, although rituximab didn’t produce sustained or substantial symptom relief, hope should not be abandoned—it still could prove its worth.

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

To reduce the use of antibiotics for respiratory tract infections, some general practitioners either don’t prescribe antibiotics or delay their use by, for example, asking the patient to wait. But some reviews have suggested that delaying prescriptions can result in worse symptom control than would the immediate use of antibiotics and could lead to higher use of antibiotics than would a no-prescription policy.

The different methods of delaying prescriptions haven’t been compared directly—is there a real benefit to delay? To find out, researchers from the University of Southampton in the United Kingdom conducted a pragmatic, open factorial trial of delayed antibiotic strategies. To their knowledge, they say, it is one of the largest so far to assess the effect of different antibiotic-prescribing strategies on symptom control and antibiotic use and the only trial so far to compare several commonly used methods of delaying antibiotic prescription.

In the study, 53 physicians and nurses in 25 practices decided in negotiation with patients whether immediate antibiotics were needed. If not, patients were randomly assigned to 1 of 4 delayed-prescribing groups: recontact for a prescription, postdated prescription, collection of the prescription, or patient led (the patient was given the prescription but advised to wait to fill it). The main groups were divided into 12 subgroups, according to 3 factors: antipyretic regimens, regular antipyretic vs “as required” dosing, and steam inhalation advice vs no advice about steam. During the study, the researchers added a strategy of “no antibiotic prescription” as another randomized comparison.

The primary outcome was symptom severity measured at the end of each day during days 2 to 4 (when symptoms of all respiratory infections are at their worst) of a 2-week symptom diary. Secondary outcomes included any antibiotic use in the 14 days after recruitment, return with worsening symptoms, and complications.

In all, 264 patients completed the main diary and documented taking antibiotics. The median day for starting was day 4 for delayed-prescription strategies and day 1 for the immediate-prescription group. In the randomized groups (no prescription and delayed-prescription strategies), the researchers observed no significant effect of strategy on symptom severity. Antibiotic use did not differ significantly between strategies. The delayed groups reported slightly higher antibiotic use than that of the no-prescription group; 26% of patients not initially prescribed antibiotics used them, compared with roughly one-third of patients given a delayed prescription. Satisfaction was higher with the patient-led and collection approaches.

Complications were slightly more common in the no-prescription group (3 of 122 patients [2.5%]), compared with the delayed-strategy groups (average 6 of 432 patients [1.4%]), and similar to the immediate-prescription group (8 of 326 patients [2.5%]).

Finding little difference in symptom control between the strategies of no prescription, immediate prescription, or delayed prescription, the researchers say, “contrasts both health professionals’ behavior in commonly requiring immediate antibiotics, and the persistently strong beliefs patients have in the effectiveness of antibiotics.”

The study was designed to be pragmatic: Patients were free to not comply with advice, but compliance was probably reasonable, the researchers say. Most patients who were asked to delay using antibiotics did not use them, and those who used antibiotics, on average, delayed for several days. Such advice is not normally measured or assessed in trials of antibiotic strategies, the researchers note. They say one of the strengths of their study is that they assessed interactions between advice about symptoms and antibiotic-prescribing strategies.

The good symptom control in the study could indicate that all patients were given structured advice about analgesic use. With “clear guidance,” the researchers conclude, any strategy of delayed prescribing is likely to result in less than 40% of patients using antibiotics. 

Source
Little P, Moore M, Kelly J, et al; PIPS Investigators. BMJ. 2014;348:g1606.
doi: 10.1136/bmj.g1606.

To reduce the use of antibiotics for respiratory tract infections, some general practitioners either don’t prescribe antibiotics or delay their use by, for example, asking the patient to wait. But some reviews have suggested that delaying prescriptions can result in worse symptom control than would the immediate use of antibiotics and could lead to higher use of antibiotics than would a no-prescription policy.

The different methods of delaying prescriptions haven’t been compared directly—is there a real benefit to delay? To find out, researchers from the University of Southampton in the United Kingdom conducted a pragmatic, open factorial trial of delayed antibiotic strategies. To their knowledge, they say, it is one of the largest so far to assess the effect of different antibiotic-prescribing strategies on symptom control and antibiotic use and the only trial so far to compare several commonly used methods of delaying antibiotic prescription.

In the study, 53 physicians and nurses in 25 practices decided in negotiation with patients whether immediate antibiotics were needed. If not, patients were randomly assigned to 1 of 4 delayed-prescribing groups: recontact for a prescription, postdated prescription, collection of the prescription, or patient led (the patient was given the prescription but advised to wait to fill it). The main groups were divided into 12 subgroups, according to 3 factors: antipyretic regimens, regular antipyretic vs “as required” dosing, and steam inhalation advice vs no advice about steam. During the study, the researchers added a strategy of “no antibiotic prescription” as another randomized comparison.

The primary outcome was symptom severity measured at the end of each day during days 2 to 4 (when symptoms of all respiratory infections are at their worst) of a 2-week symptom diary. Secondary outcomes included any antibiotic use in the 14 days after recruitment, return with worsening symptoms, and complications.

In all, 264 patients completed the main diary and documented taking antibiotics. The median day for starting was day 4 for delayed-prescription strategies and day 1 for the immediate-prescription group. In the randomized groups (no prescription and delayed-prescription strategies), the researchers observed no significant effect of strategy on symptom severity. Antibiotic use did not differ significantly between strategies. The delayed groups reported slightly higher antibiotic use than that of the no-prescription group; 26% of patients not initially prescribed antibiotics used them, compared with roughly one-third of patients given a delayed prescription. Satisfaction was higher with the patient-led and collection approaches.

Complications were slightly more common in the no-prescription group (3 of 122 patients [2.5%]), compared with the delayed-strategy groups (average 6 of 432 patients [1.4%]), and similar to the immediate-prescription group (8 of 326 patients [2.5%]).

Finding little difference in symptom control between the strategies of no prescription, immediate prescription, or delayed prescription, the researchers say, “contrasts both health professionals’ behavior in commonly requiring immediate antibiotics, and the persistently strong beliefs patients have in the effectiveness of antibiotics.”

The study was designed to be pragmatic: Patients were free to not comply with advice, but compliance was probably reasonable, the researchers say. Most patients who were asked to delay using antibiotics did not use them, and those who used antibiotics, on average, delayed for several days. Such advice is not normally measured or assessed in trials of antibiotic strategies, the researchers note. They say one of the strengths of their study is that they assessed interactions between advice about symptoms and antibiotic-prescribing strategies.

The good symptom control in the study could indicate that all patients were given structured advice about analgesic use. With “clear guidance,” the researchers conclude, any strategy of delayed prescribing is likely to result in less than 40% of patients using antibiotics. 

Source
Little P, Moore M, Kelly J, et al; PIPS Investigators. BMJ. 2014;348:g1606.
doi: 10.1136/bmj.g1606.

To reduce the use of antibiotics for respiratory tract infections, some general practitioners either don’t prescribe antibiotics or delay their use by, for example, asking the patient to wait. But some reviews have suggested that delaying prescriptions can result in worse symptom control than would the immediate use of antibiotics and could lead to higher use of antibiotics than would a no-prescription policy.

The different methods of delaying prescriptions haven’t been compared directly—is there a real benefit to delay? To find out, researchers from the University of Southampton in the United Kingdom conducted a pragmatic, open factorial trial of delayed antibiotic strategies. To their knowledge, they say, it is one of the largest so far to assess the effect of different antibiotic-prescribing strategies on symptom control and antibiotic use and the only trial so far to compare several commonly used methods of delaying antibiotic prescription.

In the study, 53 physicians and nurses in 25 practices decided in negotiation with patients whether immediate antibiotics were needed. If not, patients were randomly assigned to 1 of 4 delayed-prescribing groups: recontact for a prescription, postdated prescription, collection of the prescription, or patient led (the patient was given the prescription but advised to wait to fill it). The main groups were divided into 12 subgroups, according to 3 factors: antipyretic regimens, regular antipyretic vs “as required” dosing, and steam inhalation advice vs no advice about steam. During the study, the researchers added a strategy of “no antibiotic prescription” as another randomized comparison.

The primary outcome was symptom severity measured at the end of each day during days 2 to 4 (when symptoms of all respiratory infections are at their worst) of a 2-week symptom diary. Secondary outcomes included any antibiotic use in the 14 days after recruitment, return with worsening symptoms, and complications.

In all, 264 patients completed the main diary and documented taking antibiotics. The median day for starting was day 4 for delayed-prescription strategies and day 1 for the immediate-prescription group. In the randomized groups (no prescription and delayed-prescription strategies), the researchers observed no significant effect of strategy on symptom severity. Antibiotic use did not differ significantly between strategies. The delayed groups reported slightly higher antibiotic use than that of the no-prescription group; 26% of patients not initially prescribed antibiotics used them, compared with roughly one-third of patients given a delayed prescription. Satisfaction was higher with the patient-led and collection approaches.

Complications were slightly more common in the no-prescription group (3 of 122 patients [2.5%]), compared with the delayed-strategy groups (average 6 of 432 patients [1.4%]), and similar to the immediate-prescription group (8 of 326 patients [2.5%]).

Finding little difference in symptom control between the strategies of no prescription, immediate prescription, or delayed prescription, the researchers say, “contrasts both health professionals’ behavior in commonly requiring immediate antibiotics, and the persistently strong beliefs patients have in the effectiveness of antibiotics.”

The study was designed to be pragmatic: Patients were free to not comply with advice, but compliance was probably reasonable, the researchers say. Most patients who were asked to delay using antibiotics did not use them, and those who used antibiotics, on average, delayed for several days. Such advice is not normally measured or assessed in trials of antibiotic strategies, the researchers note. They say one of the strengths of their study is that they assessed interactions between advice about symptoms and antibiotic-prescribing strategies.

The good symptom control in the study could indicate that all patients were given structured advice about analgesic use. With “clear guidance,” the researchers conclude, any strategy of delayed prescribing is likely to result in less than 40% of patients using antibiotics. 

Source
Little P, Moore M, Kelly J, et al; PIPS Investigators. BMJ. 2014;348:g1606.
doi: 10.1136/bmj.g1606.

Because unfractionated heparin (UFH), the main antithrombotic therapy for patients undergoing percutaneous coronary intervention (PCI), has major bleeding complications associated with higher mortality, bivalirudin has attracted considerable interest. Although the benefits of bivalirudin have been well established in terms of bleeding complications, its impact on mortality is less certain, say researchers from the University of Padua Medical School in Padua, Careggi Hospital in Florence, Papa Giovanni XXIII Hospital in Bergamo, and the Catholic University of the Sacred Heart in Rome, all in Italy; Weil Cornell Medical College in Brooklyn, Columbia University Medical Center, and the Cardiovascular Research Foundation, all in New York; and Radboud University Medical Center, Nijmegen, in The Netherlands. They add that the impact of bivalirudin on mortality, myocardial infarction (MI), and even major bleeding complications as a function of baseline hemorrhagic risk has not been studied.

The researchers say theirs is the largest meta-analysis (12 randomized trials involving 33,261 patients), to their knowledge, of trials exploring outcomes of patients undergoing bivalirudin-supported PCI. It is also the first meta-regression evaluating the efficacy and safety of bivalirudin compared with UFH as a function of the baseline hemorrhagic risk of patients treated with PCI.

Bivalirudin significantly reduced major and minor bleeding (P < .001 for both), but this analysis extends this finding by showing that bivalirudin is associated with lower bleeding regardless of baseline hemorrhagic risk. However, the benefits of the drug were not significantly different from those of UFH in terms of 30-day mortality or MI. Nonetheless, the analysis showed that the higher the baseline hemorrhagic risk, the larger the incremental benefit of bivalirudin over UFH.

Source
Tarantini G, Brener SJ, Barioli A, et al. Am Heart J. 2014;167(3):401-412.e6.
doi: 10.1016/j.ahj.2013.11.013.

Because unfractionated heparin (UFH), the main antithrombotic therapy for patients undergoing percutaneous coronary intervention (PCI), has major bleeding complications associated with higher mortality, bivalirudin has attracted considerable interest. Although the benefits of bivalirudin have been well established in terms of bleeding complications, its impact on mortality is less certain, say researchers from the University of Padua Medical School in Padua, Careggi Hospital in Florence, Papa Giovanni XXIII Hospital in Bergamo, and the Catholic University of the Sacred Heart in Rome, all in Italy; Weil Cornell Medical College in Brooklyn, Columbia University Medical Center, and the Cardiovascular Research Foundation, all in New York; and Radboud University Medical Center, Nijmegen, in The Netherlands. They add that the impact of bivalirudin on mortality, myocardial infarction (MI), and even major bleeding complications as a function of baseline hemorrhagic risk has not been studied.

The researchers say theirs is the largest meta-analysis (12 randomized trials involving 33,261 patients), to their knowledge, of trials exploring outcomes of patients undergoing bivalirudin-supported PCI. It is also the first meta-regression evaluating the efficacy and safety of bivalirudin compared with UFH as a function of the baseline hemorrhagic risk of patients treated with PCI.

Bivalirudin significantly reduced major and minor bleeding (P < .001 for both), but this analysis extends this finding by showing that bivalirudin is associated with lower bleeding regardless of baseline hemorrhagic risk. However, the benefits of the drug were not significantly different from those of UFH in terms of 30-day mortality or MI. Nonetheless, the analysis showed that the higher the baseline hemorrhagic risk, the larger the incremental benefit of bivalirudin over UFH.

Source
Tarantini G, Brener SJ, Barioli A, et al. Am Heart J. 2014;167(3):401-412.e6.
doi: 10.1016/j.ahj.2013.11.013.

Because unfractionated heparin (UFH), the main antithrombotic therapy for patients undergoing percutaneous coronary intervention (PCI), has major bleeding complications associated with higher mortality, bivalirudin has attracted considerable interest. Although the benefits of bivalirudin have been well established in terms of bleeding complications, its impact on mortality is less certain, say researchers from the University of Padua Medical School in Padua, Careggi Hospital in Florence, Papa Giovanni XXIII Hospital in Bergamo, and the Catholic University of the Sacred Heart in Rome, all in Italy; Weil Cornell Medical College in Brooklyn, Columbia University Medical Center, and the Cardiovascular Research Foundation, all in New York; and Radboud University Medical Center, Nijmegen, in The Netherlands. They add that the impact of bivalirudin on mortality, myocardial infarction (MI), and even major bleeding complications as a function of baseline hemorrhagic risk has not been studied.

The researchers say theirs is the largest meta-analysis (12 randomized trials involving 33,261 patients), to their knowledge, of trials exploring outcomes of patients undergoing bivalirudin-supported PCI. It is also the first meta-regression evaluating the efficacy and safety of bivalirudin compared with UFH as a function of the baseline hemorrhagic risk of patients treated with PCI.

Bivalirudin significantly reduced major and minor bleeding (P < .001 for both), but this analysis extends this finding by showing that bivalirudin is associated with lower bleeding regardless of baseline hemorrhagic risk. However, the benefits of the drug were not significantly different from those of UFH in terms of 30-day mortality or MI. Nonetheless, the analysis showed that the higher the baseline hemorrhagic risk, the larger the incremental benefit of bivalirudin over UFH.

Source
Tarantini G, Brener SJ, Barioli A, et al. Am Heart J. 2014;167(3):401-412.e6.
doi: 10.1016/j.ahj.2013.11.013.

About one-quarter of patients reported missing a dose, mistiming a dose, or reducing a dose of basal insulin in the past 30 days, according to an online survey of the multinational Global Attitude of Patients and Physicians. Researchers from St. Michael’s Hospital in Toronto; the University of Toronto; Novo Nordisk, Canada in Mississauga; and the University of Manitoba, all in Canada, analyzed a Canadian cohort of 156 patients and 202 health care professionals (HCPs). The survey was intended to provide real-world data on how patients prevent or manage hypoglycemia and how they feel about it—then, to compare those responses with what physicians think patients are doing.

Most patients (92%) felt they had moderate or good control of their diabetes. Many (80%) reported having experienced a hypoglycemic event they treated themselves; 33% of these respondents reported an event in the past month. When asked about the last time they had taken a basal insulin dose irregularly, 23% of patients reported missing a dose, 26% reported mistiming a dose, and 13% said they had reduced a dose in the past 30 days. On the last occasion of irregular use, 74% had reduced their basal insulin dose intentionally, usually for hypoglycemia or the risk of hypoglycemia.

Of 51 patients who had experienced at least 1 self-treated hypoglycemic event in the past 30 days, 27% experienced ≥ 5 events. Most patients (88%) experienced at least 1 daytime event; 47% experienced at least 1 hypoglycemic event at night.

Patients who responded to a hypoglycemic event, on average, missed 1.2 doses, mistimed 2.1 doses, or reduced 1.7 doses. Half said they also increased blood glucose monitoring.

The physicians, for their part, had a good grasp on what the patients were doing. They reported similar levels of patient-reported dosing irregularities, and more than 90% of physicians said they recommended patients temporarily reduce their insulin doses to manage their hypoglycemia.

Where the 2 groups differed, however, was in the attitude toward hypoglycemic events. Many patients reported being very or somewhat worried about having an event, more worried than the physicians thought. For example, 44% of patients were concerned about self-treated hypoglycemia in a place where there was no access to food or drink; the physicians reported 15% of patients being concerned about this. Only when it came to daytime hypoglycemia were the patients less concerned than the doctors thought they were.

By and large, the responses indicated that patients were probably following their doctors’ advice. Still, the researchers say, the findings also indicated that patients might benefit from HCPs asking more direct questions about any worries associated with self-treated hypoglycemic events. That could help ensure “that it is not fear of hypoglycemia but rather appropriate responses to changes in schedule, food intake, physical activity, and so forth that prompt dosing changes,” the researchers note. The researchers suggest that patients need more education about considering what is precipitating the hypoglycemic event so they can decide on the appropriate response.

Source
Leiter LA, Boras D, Woo VC. Can J Diabetes. 2014;38(1):38-44.
doi: 10.1016/j.jcjd.2013.08.270.

About one-quarter of patients reported missing a dose, mistiming a dose, or reducing a dose of basal insulin in the past 30 days, according to an online survey of the multinational Global Attitude of Patients and Physicians. Researchers from St. Michael’s Hospital in Toronto; the University of Toronto; Novo Nordisk, Canada in Mississauga; and the University of Manitoba, all in Canada, analyzed a Canadian cohort of 156 patients and 202 health care professionals (HCPs). The survey was intended to provide real-world data on how patients prevent or manage hypoglycemia and how they feel about it—then, to compare those responses with what physicians think patients are doing.

Most patients (92%) felt they had moderate or good control of their diabetes. Many (80%) reported having experienced a hypoglycemic event they treated themselves; 33% of these respondents reported an event in the past month. When asked about the last time they had taken a basal insulin dose irregularly, 23% of patients reported missing a dose, 26% reported mistiming a dose, and 13% said they had reduced a dose in the past 30 days. On the last occasion of irregular use, 74% had reduced their basal insulin dose intentionally, usually for hypoglycemia or the risk of hypoglycemia.

Of 51 patients who had experienced at least 1 self-treated hypoglycemic event in the past 30 days, 27% experienced ≥ 5 events. Most patients (88%) experienced at least 1 daytime event; 47% experienced at least 1 hypoglycemic event at night.

Patients who responded to a hypoglycemic event, on average, missed 1.2 doses, mistimed 2.1 doses, or reduced 1.7 doses. Half said they also increased blood glucose monitoring.

The physicians, for their part, had a good grasp on what the patients were doing. They reported similar levels of patient-reported dosing irregularities, and more than 90% of physicians said they recommended patients temporarily reduce their insulin doses to manage their hypoglycemia.

Where the 2 groups differed, however, was in the attitude toward hypoglycemic events. Many patients reported being very or somewhat worried about having an event, more worried than the physicians thought. For example, 44% of patients were concerned about self-treated hypoglycemia in a place where there was no access to food or drink; the physicians reported 15% of patients being concerned about this. Only when it came to daytime hypoglycemia were the patients less concerned than the doctors thought they were.

By and large, the responses indicated that patients were probably following their doctors’ advice. Still, the researchers say, the findings also indicated that patients might benefit from HCPs asking more direct questions about any worries associated with self-treated hypoglycemic events. That could help ensure “that it is not fear of hypoglycemia but rather appropriate responses to changes in schedule, food intake, physical activity, and so forth that prompt dosing changes,” the researchers note. The researchers suggest that patients need more education about considering what is precipitating the hypoglycemic event so they can decide on the appropriate response.

Source
Leiter LA, Boras D, Woo VC. Can J Diabetes. 2014;38(1):38-44.
doi: 10.1016/j.jcjd.2013.08.270.

About one-quarter of patients reported missing a dose, mistiming a dose, or reducing a dose of basal insulin in the past 30 days, according to an online survey of the multinational Global Attitude of Patients and Physicians. Researchers from St. Michael’s Hospital in Toronto; the University of Toronto; Novo Nordisk, Canada in Mississauga; and the University of Manitoba, all in Canada, analyzed a Canadian cohort of 156 patients and 202 health care professionals (HCPs). The survey was intended to provide real-world data on how patients prevent or manage hypoglycemia and how they feel about it—then, to compare those responses with what physicians think patients are doing.

Most patients (92%) felt they had moderate or good control of their diabetes. Many (80%) reported having experienced a hypoglycemic event they treated themselves; 33% of these respondents reported an event in the past month. When asked about the last time they had taken a basal insulin dose irregularly, 23% of patients reported missing a dose, 26% reported mistiming a dose, and 13% said they had reduced a dose in the past 30 days. On the last occasion of irregular use, 74% had reduced their basal insulin dose intentionally, usually for hypoglycemia or the risk of hypoglycemia.

Of 51 patients who had experienced at least 1 self-treated hypoglycemic event in the past 30 days, 27% experienced ≥ 5 events. Most patients (88%) experienced at least 1 daytime event; 47% experienced at least 1 hypoglycemic event at night.

Patients who responded to a hypoglycemic event, on average, missed 1.2 doses, mistimed 2.1 doses, or reduced 1.7 doses. Half said they also increased blood glucose monitoring.

The physicians, for their part, had a good grasp on what the patients were doing. They reported similar levels of patient-reported dosing irregularities, and more than 90% of physicians said they recommended patients temporarily reduce their insulin doses to manage their hypoglycemia.

Where the 2 groups differed, however, was in the attitude toward hypoglycemic events. Many patients reported being very or somewhat worried about having an event, more worried than the physicians thought. For example, 44% of patients were concerned about self-treated hypoglycemia in a place where there was no access to food or drink; the physicians reported 15% of patients being concerned about this. Only when it came to daytime hypoglycemia were the patients less concerned than the doctors thought they were.

By and large, the responses indicated that patients were probably following their doctors’ advice. Still, the researchers say, the findings also indicated that patients might benefit from HCPs asking more direct questions about any worries associated with self-treated hypoglycemic events. That could help ensure “that it is not fear of hypoglycemia but rather appropriate responses to changes in schedule, food intake, physical activity, and so forth that prompt dosing changes,” the researchers note. The researchers suggest that patients need more education about considering what is precipitating the hypoglycemic event so they can decide on the appropriate response.

Source
Leiter LA, Boras D, Woo VC. Can J Diabetes. 2014;38(1):38-44.
doi: 10.1016/j.jcjd.2013.08.270.

Prenatal probiotics have been shown to help prevent atopic dermatitis, but are they effective in preventing asthma? Unfortunately, it seems not, say researchers from the University of Alberta, the University of Manitoba, and the Manitoba Institute of Child Health, all in Canada. The researchers analyzed data from randomized controlled trials of pregnant women or healthy infants but found no evidence to support a protective association between perinatal probiotics and childhood asthma or wheeze.

In 9 trials involving 3,257 children, the incidence of doctor-diagnosed asthma at final assessment was 11.2% among patients who received probiotics and 10.2% among those receiving placebo. In 9 trials involving 1,949 children, incident wheeze was similar after supplementation with probiotics (35%) vs placebo (31%). Two other trials reported an increased risk of recurrent wheeze after probiotics, and a third reported a lower risk.

However, although “inadequately reported,” the researchers say, probiotics could be associated with clinically relevant increases in lower respiratory tract infections (RTIs). Six trials involving 1,364 children that had data on lower RTIs found an incidence of 14.5% among children who received probiotics, compared with 13.2% among those who received placebo. Notably, the researchers say, 4 of those trials documented lower RTIs nonsystematically as adverse events rather than as primary or secondary outcomes. When those 4 trials were excluded, the pooled risk ratio of lower RTI associated with probiotics was 1.11.

Subgroup analyses revealed that the effect of probiotics was similar regardless of timing (prenatal, postnatal, or both) or person receiving the intervention (mother, infant, or both). The researchers also note that the large variety of strains, combinations, and doses tested made it hard to assess efficacy of specific probiotic organisms.

Future research, the authors say, could help identify infants most likely to benefit from probiotics. They cite research that has shown probiotics were protective against IgE-associated allergic disease in infants delivered by cesarean section (whose gut microbiota is disrupted) but not in their vaginally delivered counterparts. They suggest that probiotics might play a useful role in other microbiota-disrupting exposures, such as formula feeding and antibiotic treatment. But so far, they conclude, evidence is insufficient to support recommending perinatal probiotics for primary prevention of asthma or wheeze. 

Source
Azad MB, Coneys JG, Kozyrskyj AL, et al. BMJ. 2013;347:f6471.
doi: 10.1136/bmj.f6471.

Prenatal probiotics have been shown to help prevent atopic dermatitis, but are they effective in preventing asthma? Unfortunately, it seems not, say researchers from the University of Alberta, the University of Manitoba, and the Manitoba Institute of Child Health, all in Canada. The researchers analyzed data from randomized controlled trials of pregnant women or healthy infants but found no evidence to support a protective association between perinatal probiotics and childhood asthma or wheeze.

In 9 trials involving 3,257 children, the incidence of doctor-diagnosed asthma at final assessment was 11.2% among patients who received probiotics and 10.2% among those receiving placebo. In 9 trials involving 1,949 children, incident wheeze was similar after supplementation with probiotics (35%) vs placebo (31%). Two other trials reported an increased risk of recurrent wheeze after probiotics, and a third reported a lower risk.

However, although “inadequately reported,” the researchers say, probiotics could be associated with clinically relevant increases in lower respiratory tract infections (RTIs). Six trials involving 1,364 children that had data on lower RTIs found an incidence of 14.5% among children who received probiotics, compared with 13.2% among those who received placebo. Notably, the researchers say, 4 of those trials documented lower RTIs nonsystematically as adverse events rather than as primary or secondary outcomes. When those 4 trials were excluded, the pooled risk ratio of lower RTI associated with probiotics was 1.11.

Subgroup analyses revealed that the effect of probiotics was similar regardless of timing (prenatal, postnatal, or both) or person receiving the intervention (mother, infant, or both). The researchers also note that the large variety of strains, combinations, and doses tested made it hard to assess efficacy of specific probiotic organisms.

Future research, the authors say, could help identify infants most likely to benefit from probiotics. They cite research that has shown probiotics were protective against IgE-associated allergic disease in infants delivered by cesarean section (whose gut microbiota is disrupted) but not in their vaginally delivered counterparts. They suggest that probiotics might play a useful role in other microbiota-disrupting exposures, such as formula feeding and antibiotic treatment. But so far, they conclude, evidence is insufficient to support recommending perinatal probiotics for primary prevention of asthma or wheeze. 

Source
Azad MB, Coneys JG, Kozyrskyj AL, et al. BMJ. 2013;347:f6471.
doi: 10.1136/bmj.f6471.

Prenatal probiotics have been shown to help prevent atopic dermatitis, but are they effective in preventing asthma? Unfortunately, it seems not, say researchers from the University of Alberta, the University of Manitoba, and the Manitoba Institute of Child Health, all in Canada. The researchers analyzed data from randomized controlled trials of pregnant women or healthy infants but found no evidence to support a protective association between perinatal probiotics and childhood asthma or wheeze.

In 9 trials involving 3,257 children, the incidence of doctor-diagnosed asthma at final assessment was 11.2% among patients who received probiotics and 10.2% among those receiving placebo. In 9 trials involving 1,949 children, incident wheeze was similar after supplementation with probiotics (35%) vs placebo (31%). Two other trials reported an increased risk of recurrent wheeze after probiotics, and a third reported a lower risk.

However, although “inadequately reported,” the researchers say, probiotics could be associated with clinically relevant increases in lower respiratory tract infections (RTIs). Six trials involving 1,364 children that had data on lower RTIs found an incidence of 14.5% among children who received probiotics, compared with 13.2% among those who received placebo. Notably, the researchers say, 4 of those trials documented lower RTIs nonsystematically as adverse events rather than as primary or secondary outcomes. When those 4 trials were excluded, the pooled risk ratio of lower RTI associated with probiotics was 1.11.

Subgroup analyses revealed that the effect of probiotics was similar regardless of timing (prenatal, postnatal, or both) or person receiving the intervention (mother, infant, or both). The researchers also note that the large variety of strains, combinations, and doses tested made it hard to assess efficacy of specific probiotic organisms.

Future research, the authors say, could help identify infants most likely to benefit from probiotics. They cite research that has shown probiotics were protective against IgE-associated allergic disease in infants delivered by cesarean section (whose gut microbiota is disrupted) but not in their vaginally delivered counterparts. They suggest that probiotics might play a useful role in other microbiota-disrupting exposures, such as formula feeding and antibiotic treatment. But so far, they conclude, evidence is insufficient to support recommending perinatal probiotics for primary prevention of asthma or wheeze. 

Source
Azad MB, Coneys JG, Kozyrskyj AL, et al. BMJ. 2013;347:f6471.
doi: 10.1136/bmj.f6471.

When used to treat severe psoriasis and other autoimmune diseases, infliximab is known to cause pulmonary complications, such as increased risk of infection from tuberculosis. Interstitial lung disease (ILD) has also been reported as a complication of antitumor necrosis factor-alpha (anti-TNFα), although the connection is less understood. Moreover, most published reports are about patients with rheumatoid arthritis and preexisting ILD, not psoriasis.

Researchers from Evangelismos General Hospital of Athens in Greece reported on a case of ILD in a patient with psoriasis who was treated with infliximab and who had no history of pulmonary disease.

The patient, a 64-year-old man, presented to the emergency department (ED) with general malaise, fever, persistent dry cough, and progressive exertional dyspnea for 1 week. He had been diagnosed with psoriasis a year earlier and had been treated for depression for the past 2 years. He was started on corticosteroids and cyclosporine for the psoriasis but was switched to 2 weekly intravenous (IV) doses of methotrexate (MTX). The MTX was discontinued due to ineffectiveness, and the infliximab was started. Nine days after the patient’s last MTX dose, the patient received his first IV infusion of infliximab 5 mg/kg. A second infusion of the same dose was given 2 weeks later. One week after that, the patient came to the ED and was admitted to the pulmonary clinic.

On admission, the patient had a respiratory rate of 36 breaths per minute; an arterial blood gas analysis revealed severe hypoxemia and hypocapnia. A chest examination revealed diffuse, inspiratory fine and coarse rales bilaterally. His blood chemistry was significant for increased inflammatory markers, and there were brightly erythematous psoriatic plaques on his trunk, arms, and lower legs. The rest of his physical examination was normal.

Based on the recent infliximab treatment, the low-grade fever, and elevated inflammatory markers, the patient was given broad-spectrum IV antibiotics as well as bronchodilators and furosemide. However, treatment failed to relieve his respiratory condition. The results of an extensive microbiology and immunologic workup were negative. A second thoracic computed tomography (CT) showed the ILD had progressed; a bronchoscopy was performed. Because bronchoalveolar lavage and other testing were negative for malignant cells, common pathogens, Pneumocystis carinii, fungi, and tuberculosis, the clinical team suspected infliximab-induced ILD.

Oral corticosteroid treatment (prednisone 50 mg/d) rapidly improved the patient’s oxygenation, and his symptoms resolved within a few days. One week later, a chest X-ray showed marked improvement. He was discharged on a tapering dose of prednisone. The authors note that in all 4 of the reported cases of infliximab-induced ILD in patients with psoriasis, the patients responded well to corticosteroids.

In the case of infliximab-induced ILD, the symptoms usually appear between 6 weeks and 3 months after infliximab is started, and follow the third infusion. However, the researchers note that ILD has been reported even 1 week after anti-TNFα therapy in other clinical settings, usually after the second or third infusion. In their patient, ILD symptoms appeared only 3 weeks after the first dose. The patient was a smoker, and the authors say possible undiagnosed lung disease should not be ruled out.

Similarly, the researchers say MTX may have played a role. Pulmonary toxicity attributed to anti-TNFα inhibitor usually occurs when the treatment coincides with or follows a course of MTX, which is widely known to cause acute interstitial pneumonitis. This progression has led to the hypothesis that infliximab may exacerbate the pulmonary toxicity of MTX. However, the authors note that a number of cases of anti-TNF-induced ILD have been in patients without MTX treatment. Although there was a strong temporal relationship between their patient’s symptoms and the introduction of infliximab, and the MTX course had been short, they acknowledge that only 9 days elapsed between the last MTX dose and the first dose of infliximab. Involvement of MTX can’t be ruled out in their patient, they add, “because MTX lung toxicity is both unpredictable and poorly understood.”

Infliximab is a wonder drug for patients with plaque psoriasis and psoriatic arthritis when symptoms don’t respond to traditional regimens. However, some patients are at higher risk for ILD, the authors say. Older age, smoking, systemic disease, and concomitant immunosuppressive therapy are all risk factors. Their patient had 3 of those. When deciding whether to start a patient on infliximab, they advise screening for these risk factors. When subclinical ILD is suspected, they advise an initial high-resolution chest CT and pulmonary function tests before starting anti-TNF therapy. Finally, they suggest, instruct patients on infliximab to report any new pulmonary symptoms without delay.

Source
Kakavas S, Balis E, Lazarou V, Kouvela M, Tatsis G. Heart Lung.  2013;42(6):480-482.
doi: 10.1016/j.hrtlng.2013.07.005.

When used to treat severe psoriasis and other autoimmune diseases, infliximab is known to cause pulmonary complications, such as increased risk of infection from tuberculosis. Interstitial lung disease (ILD) has also been reported as a complication of antitumor necrosis factor-alpha (anti-TNFα), although the connection is less understood. Moreover, most published reports are about patients with rheumatoid arthritis and preexisting ILD, not psoriasis.

Researchers from Evangelismos General Hospital of Athens in Greece reported on a case of ILD in a patient with psoriasis who was treated with infliximab and who had no history of pulmonary disease.

The patient, a 64-year-old man, presented to the emergency department (ED) with general malaise, fever, persistent dry cough, and progressive exertional dyspnea for 1 week. He had been diagnosed with psoriasis a year earlier and had been treated for depression for the past 2 years. He was started on corticosteroids and cyclosporine for the psoriasis but was switched to 2 weekly intravenous (IV) doses of methotrexate (MTX). The MTX was discontinued due to ineffectiveness, and the infliximab was started. Nine days after the patient’s last MTX dose, the patient received his first IV infusion of infliximab 5 mg/kg. A second infusion of the same dose was given 2 weeks later. One week after that, the patient came to the ED and was admitted to the pulmonary clinic.

On admission, the patient had a respiratory rate of 36 breaths per minute; an arterial blood gas analysis revealed severe hypoxemia and hypocapnia. A chest examination revealed diffuse, inspiratory fine and coarse rales bilaterally. His blood chemistry was significant for increased inflammatory markers, and there were brightly erythematous psoriatic plaques on his trunk, arms, and lower legs. The rest of his physical examination was normal.

Based on the recent infliximab treatment, the low-grade fever, and elevated inflammatory markers, the patient was given broad-spectrum IV antibiotics as well as bronchodilators and furosemide. However, treatment failed to relieve his respiratory condition. The results of an extensive microbiology and immunologic workup were negative. A second thoracic computed tomography (CT) showed the ILD had progressed; a bronchoscopy was performed. Because bronchoalveolar lavage and other testing were negative for malignant cells, common pathogens, Pneumocystis carinii, fungi, and tuberculosis, the clinical team suspected infliximab-induced ILD.

Oral corticosteroid treatment (prednisone 50 mg/d) rapidly improved the patient’s oxygenation, and his symptoms resolved within a few days. One week later, a chest X-ray showed marked improvement. He was discharged on a tapering dose of prednisone. The authors note that in all 4 of the reported cases of infliximab-induced ILD in patients with psoriasis, the patients responded well to corticosteroids.

In the case of infliximab-induced ILD, the symptoms usually appear between 6 weeks and 3 months after infliximab is started, and follow the third infusion. However, the researchers note that ILD has been reported even 1 week after anti-TNFα therapy in other clinical settings, usually after the second or third infusion. In their patient, ILD symptoms appeared only 3 weeks after the first dose. The patient was a smoker, and the authors say possible undiagnosed lung disease should not be ruled out.

Similarly, the researchers say MTX may have played a role. Pulmonary toxicity attributed to anti-TNFα inhibitor usually occurs when the treatment coincides with or follows a course of MTX, which is widely known to cause acute interstitial pneumonitis. This progression has led to the hypothesis that infliximab may exacerbate the pulmonary toxicity of MTX. However, the authors note that a number of cases of anti-TNF-induced ILD have been in patients without MTX treatment. Although there was a strong temporal relationship between their patient’s symptoms and the introduction of infliximab, and the MTX course had been short, they acknowledge that only 9 days elapsed between the last MTX dose and the first dose of infliximab. Involvement of MTX can’t be ruled out in their patient, they add, “because MTX lung toxicity is both unpredictable and poorly understood.”

Infliximab is a wonder drug for patients with plaque psoriasis and psoriatic arthritis when symptoms don’t respond to traditional regimens. However, some patients are at higher risk for ILD, the authors say. Older age, smoking, systemic disease, and concomitant immunosuppressive therapy are all risk factors. Their patient had 3 of those. When deciding whether to start a patient on infliximab, they advise screening for these risk factors. When subclinical ILD is suspected, they advise an initial high-resolution chest CT and pulmonary function tests before starting anti-TNF therapy. Finally, they suggest, instruct patients on infliximab to report any new pulmonary symptoms without delay.

Source
Kakavas S, Balis E, Lazarou V, Kouvela M, Tatsis G. Heart Lung.  2013;42(6):480-482.
doi: 10.1016/j.hrtlng.2013.07.005.

When used to treat severe psoriasis and other autoimmune diseases, infliximab is known to cause pulmonary complications, such as increased risk of infection from tuberculosis. Interstitial lung disease (ILD) has also been reported as a complication of antitumor necrosis factor-alpha (anti-TNFα), although the connection is less understood. Moreover, most published reports are about patients with rheumatoid arthritis and preexisting ILD, not psoriasis.

Researchers from Evangelismos General Hospital of Athens in Greece reported on a case of ILD in a patient with psoriasis who was treated with infliximab and who had no history of pulmonary disease.

The patient, a 64-year-old man, presented to the emergency department (ED) with general malaise, fever, persistent dry cough, and progressive exertional dyspnea for 1 week. He had been diagnosed with psoriasis a year earlier and had been treated for depression for the past 2 years. He was started on corticosteroids and cyclosporine for the psoriasis but was switched to 2 weekly intravenous (IV) doses of methotrexate (MTX). The MTX was discontinued due to ineffectiveness, and the infliximab was started. Nine days after the patient’s last MTX dose, the patient received his first IV infusion of infliximab 5 mg/kg. A second infusion of the same dose was given 2 weeks later. One week after that, the patient came to the ED and was admitted to the pulmonary clinic.

On admission, the patient had a respiratory rate of 36 breaths per minute; an arterial blood gas analysis revealed severe hypoxemia and hypocapnia. A chest examination revealed diffuse, inspiratory fine and coarse rales bilaterally. His blood chemistry was significant for increased inflammatory markers, and there were brightly erythematous psoriatic plaques on his trunk, arms, and lower legs. The rest of his physical examination was normal.

Based on the recent infliximab treatment, the low-grade fever, and elevated inflammatory markers, the patient was given broad-spectrum IV antibiotics as well as bronchodilators and furosemide. However, treatment failed to relieve his respiratory condition. The results of an extensive microbiology and immunologic workup were negative. A second thoracic computed tomography (CT) showed the ILD had progressed; a bronchoscopy was performed. Because bronchoalveolar lavage and other testing were negative for malignant cells, common pathogens, Pneumocystis carinii, fungi, and tuberculosis, the clinical team suspected infliximab-induced ILD.

Oral corticosteroid treatment (prednisone 50 mg/d) rapidly improved the patient’s oxygenation, and his symptoms resolved within a few days. One week later, a chest X-ray showed marked improvement. He was discharged on a tapering dose of prednisone. The authors note that in all 4 of the reported cases of infliximab-induced ILD in patients with psoriasis, the patients responded well to corticosteroids.

In the case of infliximab-induced ILD, the symptoms usually appear between 6 weeks and 3 months after infliximab is started, and follow the third infusion. However, the researchers note that ILD has been reported even 1 week after anti-TNFα therapy in other clinical settings, usually after the second or third infusion. In their patient, ILD symptoms appeared only 3 weeks after the first dose. The patient was a smoker, and the authors say possible undiagnosed lung disease should not be ruled out.

Similarly, the researchers say MTX may have played a role. Pulmonary toxicity attributed to anti-TNFα inhibitor usually occurs when the treatment coincides with or follows a course of MTX, which is widely known to cause acute interstitial pneumonitis. This progression has led to the hypothesis that infliximab may exacerbate the pulmonary toxicity of MTX. However, the authors note that a number of cases of anti-TNF-induced ILD have been in patients without MTX treatment. Although there was a strong temporal relationship between their patient’s symptoms and the introduction of infliximab, and the MTX course had been short, they acknowledge that only 9 days elapsed between the last MTX dose and the first dose of infliximab. Involvement of MTX can’t be ruled out in their patient, they add, “because MTX lung toxicity is both unpredictable and poorly understood.”

Infliximab is a wonder drug for patients with plaque psoriasis and psoriatic arthritis when symptoms don’t respond to traditional regimens. However, some patients are at higher risk for ILD, the authors say. Older age, smoking, systemic disease, and concomitant immunosuppressive therapy are all risk factors. Their patient had 3 of those. When deciding whether to start a patient on infliximab, they advise screening for these risk factors. When subclinical ILD is suspected, they advise an initial high-resolution chest CT and pulmonary function tests before starting anti-TNF therapy. Finally, they suggest, instruct patients on infliximab to report any new pulmonary symptoms without delay.

Source
Kakavas S, Balis E, Lazarou V, Kouvela M, Tatsis G. Heart Lung.  2013;42(6):480-482.
doi: 10.1016/j.hrtlng.2013.07.005.

Most studies of women who have been treated for menorrhagia find that the women feel the maximum benefits in quality of life (QOL) come in the first 5 years after treatment, but those studies haven’t gone beyond 10 years in follow-up. Finnish researchers who reinterviewed study participants 10 years after their treatment found that the effects of treatment (hysterectomy or levonorgestrel-releasing intrauterine system [LNG-IUS]) had indeed peaked in the first 5 years. Any decline in health-related (HR) QOL thereafter, they say, was probably due to aging.

In their study, 236 women aged 35 to 49 years with menorrhagia were referred to 5 university hospitals in Finland and randomly assigned to treatment with hysterectomy or LNG-IUS. Follow-up visits took place at 6 months, 12 months, 5 years, and 10 years. The women completed questionnaires at each visit, including the Finnish version of the RAND 36-Item Health Survey (RAND-36) and the 5-Dimensional EuroQol (EQ-5D), which measures morbidity, self-care, usual activities, pain, and mood. Other scales measured anxiety, depression, and sexuality-related factors.

The baseline EQ-5D and RAND-36 scores of the study participants were significantly lower, the authors report, than the scores of age-matched Finnish women and, in fact, similar to the scores of women with chronic illness. Treating their menorrhagia boosted HRQOL and psychosocial well-being scores most strongly in the first year. However, between the fifth and tenth years, HRQOL declined by most measures. Sexual functioning was “substantially” impaired, for instance. Nevertheless, the researchers say, the HRQOL scores were still above or at least at the same level as baseline. The key seems to be that 10 years after the study, most of the women had entered or passed menopause (although follicle-stimulating hormone values were not measured).

Both treatments improved HRQOL, the researchers say. But, when helping a patient decide whether to have a hysterectomy or the LNG-IUS, they add that their findings showed that the LNG-IUS costs 31% less.

Source
Heliövaara-Peippo S, Hurskainen R, Teperi J, et al. Am J Obstet Gynecol.  2013;209(6):535.e1-535.e14.
doi: 10.1016/j.ajog.2013.08.041.

Most studies of women who have been treated for menorrhagia find that the women feel the maximum benefits in quality of life (QOL) come in the first 5 years after treatment, but those studies haven’t gone beyond 10 years in follow-up. Finnish researchers who reinterviewed study participants 10 years after their treatment found that the effects of treatment (hysterectomy or levonorgestrel-releasing intrauterine system [LNG-IUS]) had indeed peaked in the first 5 years. Any decline in health-related (HR) QOL thereafter, they say, was probably due to aging.

In their study, 236 women aged 35 to 49 years with menorrhagia were referred to 5 university hospitals in Finland and randomly assigned to treatment with hysterectomy or LNG-IUS. Follow-up visits took place at 6 months, 12 months, 5 years, and 10 years. The women completed questionnaires at each visit, including the Finnish version of the RAND 36-Item Health Survey (RAND-36) and the 5-Dimensional EuroQol (EQ-5D), which measures morbidity, self-care, usual activities, pain, and mood. Other scales measured anxiety, depression, and sexuality-related factors.

The baseline EQ-5D and RAND-36 scores of the study participants were significantly lower, the authors report, than the scores of age-matched Finnish women and, in fact, similar to the scores of women with chronic illness. Treating their menorrhagia boosted HRQOL and psychosocial well-being scores most strongly in the first year. However, between the fifth and tenth years, HRQOL declined by most measures. Sexual functioning was “substantially” impaired, for instance. Nevertheless, the researchers say, the HRQOL scores were still above or at least at the same level as baseline. The key seems to be that 10 years after the study, most of the women had entered or passed menopause (although follicle-stimulating hormone values were not measured).

Both treatments improved HRQOL, the researchers say. But, when helping a patient decide whether to have a hysterectomy or the LNG-IUS, they add that their findings showed that the LNG-IUS costs 31% less.

Source
Heliövaara-Peippo S, Hurskainen R, Teperi J, et al. Am J Obstet Gynecol.  2013;209(6):535.e1-535.e14.
doi: 10.1016/j.ajog.2013.08.041.

Most studies of women who have been treated for menorrhagia find that the women feel the maximum benefits in quality of life (QOL) come in the first 5 years after treatment, but those studies haven’t gone beyond 10 years in follow-up. Finnish researchers who reinterviewed study participants 10 years after their treatment found that the effects of treatment (hysterectomy or levonorgestrel-releasing intrauterine system [LNG-IUS]) had indeed peaked in the first 5 years. Any decline in health-related (HR) QOL thereafter, they say, was probably due to aging.

In their study, 236 women aged 35 to 49 years with menorrhagia were referred to 5 university hospitals in Finland and randomly assigned to treatment with hysterectomy or LNG-IUS. Follow-up visits took place at 6 months, 12 months, 5 years, and 10 years. The women completed questionnaires at each visit, including the Finnish version of the RAND 36-Item Health Survey (RAND-36) and the 5-Dimensional EuroQol (EQ-5D), which measures morbidity, self-care, usual activities, pain, and mood. Other scales measured anxiety, depression, and sexuality-related factors.

The baseline EQ-5D and RAND-36 scores of the study participants were significantly lower, the authors report, than the scores of age-matched Finnish women and, in fact, similar to the scores of women with chronic illness. Treating their menorrhagia boosted HRQOL and psychosocial well-being scores most strongly in the first year. However, between the fifth and tenth years, HRQOL declined by most measures. Sexual functioning was “substantially” impaired, for instance. Nevertheless, the researchers say, the HRQOL scores were still above or at least at the same level as baseline. The key seems to be that 10 years after the study, most of the women had entered or passed menopause (although follicle-stimulating hormone values were not measured).

Both treatments improved HRQOL, the researchers say. But, when helping a patient decide whether to have a hysterectomy or the LNG-IUS, they add that their findings showed that the LNG-IUS costs 31% less.

Source
Heliövaara-Peippo S, Hurskainen R, Teperi J, et al. Am J Obstet Gynecol.  2013;209(6):535.e1-535.e14.
doi: 10.1016/j.ajog.2013.08.041.

Nonsteroidal anti-inflammatories (NSAIDs) are often used to treat the pain and inflammation of osteoarthritis, but they may have another effect: relieving depression.

Depression is 2 to 3 times more prevalent in patients with osteoarthritis than in other groups. Recent research has suggested that NSAIDs—via an association between cytokine release and prostaglandin synthesis in depression—may have a role to play in relieving symptoms of depression. For instance, studies have shown a benefit of NSAIDs as augmentation therapy in patients taking concurrent antidepressant therapy.

Researchers from Mount Sinai School of Medicine in New York City; St. George’s University in Grenada; University of Toronto in Canada; Case Western Reserve University in Cleveland, Ohio; and New York University in New York City looked at data from 5 trials that involved 1,497 patients who had osteoarthritis. Each multicenter, double-blind, placebo-controlled trial was 6 weeks long. Patients were randomly assigned to placebo, ibuprofen 800 mg 3 times daily, naproxen 500 mg twice daily, or celecoxib 200 mg daily. All patients were screened at baseline for depression using the Patient Health Questionnaire-9 (PHQ-9) and were assessed at weeks 2 and 6. The outcome measured was a change in PHQ-9 score at week 6 or early termination.

At baseline and week 6, the median PHQ-9 score was similar in all 3 groups. After 6 weeks of treatment, the researchers observed a significant trend toward lower scores among patients on ibuprofen or naproxen (– 0.31) and celecoxib (– 0.61) (P = .039). They also found a trend toward significant treatment effect of all NSAIDs compared with placebo.

Although their findings are “intriguing” and support the putative connection between depression and inflammation, the researchers don’t recommend routine population-based screening for depression and prophylactic NSAID use in those at high risk for depression. They do, however, underscore the importance of NSAID therapy in osteoarthritis, especially since the benefits may go beyond reducing inflammation.

Source
Iyengar RL, Gandhi S, Aneja A, et al. Am J Med. 2013;126(11):1017.e11-1017.e18.
doi: 10.1016/j.amjmed.2013.02.037.

Nonsteroidal anti-inflammatories (NSAIDs) are often used to treat the pain and inflammation of osteoarthritis, but they may have another effect: relieving depression.

Depression is 2 to 3 times more prevalent in patients with osteoarthritis than in other groups. Recent research has suggested that NSAIDs—via an association between cytokine release and prostaglandin synthesis in depression—may have a role to play in relieving symptoms of depression. For instance, studies have shown a benefit of NSAIDs as augmentation therapy in patients taking concurrent antidepressant therapy.

Researchers from Mount Sinai School of Medicine in New York City; St. George’s University in Grenada; University of Toronto in Canada; Case Western Reserve University in Cleveland, Ohio; and New York University in New York City looked at data from 5 trials that involved 1,497 patients who had osteoarthritis. Each multicenter, double-blind, placebo-controlled trial was 6 weeks long. Patients were randomly assigned to placebo, ibuprofen 800 mg 3 times daily, naproxen 500 mg twice daily, or celecoxib 200 mg daily. All patients were screened at baseline for depression using the Patient Health Questionnaire-9 (PHQ-9) and were assessed at weeks 2 and 6. The outcome measured was a change in PHQ-9 score at week 6 or early termination.

At baseline and week 6, the median PHQ-9 score was similar in all 3 groups. After 6 weeks of treatment, the researchers observed a significant trend toward lower scores among patients on ibuprofen or naproxen (– 0.31) and celecoxib (– 0.61) (P = .039). They also found a trend toward significant treatment effect of all NSAIDs compared with placebo.

Although their findings are “intriguing” and support the putative connection between depression and inflammation, the researchers don’t recommend routine population-based screening for depression and prophylactic NSAID use in those at high risk for depression. They do, however, underscore the importance of NSAID therapy in osteoarthritis, especially since the benefits may go beyond reducing inflammation.

Source
Iyengar RL, Gandhi S, Aneja A, et al. Am J Med. 2013;126(11):1017.e11-1017.e18.
doi: 10.1016/j.amjmed.2013.02.037.

Nonsteroidal anti-inflammatories (NSAIDs) are often used to treat the pain and inflammation of osteoarthritis, but they may have another effect: relieving depression.

Depression is 2 to 3 times more prevalent in patients with osteoarthritis than in other groups. Recent research has suggested that NSAIDs—via an association between cytokine release and prostaglandin synthesis in depression—may have a role to play in relieving symptoms of depression. For instance, studies have shown a benefit of NSAIDs as augmentation therapy in patients taking concurrent antidepressant therapy.

Researchers from Mount Sinai School of Medicine in New York City; St. George’s University in Grenada; University of Toronto in Canada; Case Western Reserve University in Cleveland, Ohio; and New York University in New York City looked at data from 5 trials that involved 1,497 patients who had osteoarthritis. Each multicenter, double-blind, placebo-controlled trial was 6 weeks long. Patients were randomly assigned to placebo, ibuprofen 800 mg 3 times daily, naproxen 500 mg twice daily, or celecoxib 200 mg daily. All patients were screened at baseline for depression using the Patient Health Questionnaire-9 (PHQ-9) and were assessed at weeks 2 and 6. The outcome measured was a change in PHQ-9 score at week 6 or early termination.

At baseline and week 6, the median PHQ-9 score was similar in all 3 groups. After 6 weeks of treatment, the researchers observed a significant trend toward lower scores among patients on ibuprofen or naproxen (– 0.31) and celecoxib (– 0.61) (P = .039). They also found a trend toward significant treatment effect of all NSAIDs compared with placebo.

Although their findings are “intriguing” and support the putative connection between depression and inflammation, the researchers don’t recommend routine population-based screening for depression and prophylactic NSAID use in those at high risk for depression. They do, however, underscore the importance of NSAID therapy in osteoarthritis, especially since the benefits may go beyond reducing inflammation.

Source
Iyengar RL, Gandhi S, Aneja A, et al. Am J Med. 2013;126(11):1017.e11-1017.e18.
doi: 10.1016/j.amjmed.2013.02.037.

There’s no gold standard list of drugs that affect cognition in cognitively normal older adults, say researchers from St. Louis College of Pharmacy, Knight Alzheimer’s Disease Research Center, and Washington University School of Medicine, all in St. Louis, Missouri. That means physicians and pharmacists must rely on prescribing guides, such as the Beers criteria, which are based on consensus but lack supporting data. So as a “first step in addressing this lack of knowledge,” the researchers examined the long-term effects of the top 100 medications used by 4,414 participants in the National Alzheimer’s Coordinating Center database. They found that roughly 10% of those drugs were associated with long-term changes in cognition.

The researchers divided the patients into 4 groups: Group 1 was not taking the drug at visit 1 but was at visit 2; Group 2 stopped taking the drug between visit 1 and visit 2; Group 3 did not take the drug; and Group 4 was taking the drug at both visits. Composite scores were constructed from 10 psychometric tests. The researchers looked at change in cognition from the baseline visit to the follow-up visit, also looking for changes in or maintenance of the use of each medication. The average time between assessments was 1.2 years.

Nine drugs were associated with a statistically significant difference between at least 2 of the 4 study groups (P < .05). Naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline were all associated with improved psychometric performance. Bupropion, oxybutynin, and furosemide were associated with declines. Ferrous sulfate was associated with changes in attention, processing speed, and episodic memory, whereas the other 8 drugs were associated mainly with changes in attention and processing speed.

The drugs that improved cognition did so by a variety of proposed mechanisms. Naproxen may have improved scores by relieving pain, which can impede performance. Vitamin D deficiency is linked to reduced cognition in older adults, and ferrous sulfate is used to treat anemia; correcting those deficiencies may have helped cognition. Potassium chloride is used to treat or prevent hypokalemia, which can lead to confusion and cognitive problems; in this study, participants who stopped taking potassium showed drops in change scores compared with those who continued taking it.

Flax was an outlier in that the researchers were puzzled by its connection to better cognition. They did note, however, that people taking flax seed were also usually taking calcium-vitamin D. They hypothesize that people who take flax are likely to take other medicines or supplements that improve cognition. Sertraline has been shown to improve immediate and delayed verbal recall in older adults and to have a better effect on cognition than other selective serotonin reuptake inhibitors.

Some of their findings were new, the researchers say, such as the potential positive effects of ferrous sulfate. Similarly, bupropion has not previously been linked to negative effects on cognition in older adults. Such data deserve more examination, they say. Future studies may also show whether those drugs could delay the onset of incident dementia. 

Source
Obermann KR, Morris JC, Roe CM. Alzheimers Dement. 2013;9(6):724-732.
doi: 10.1016/j.jalz.2012.12.002.

There’s no gold standard list of drugs that affect cognition in cognitively normal older adults, say researchers from St. Louis College of Pharmacy, Knight Alzheimer’s Disease Research Center, and Washington University School of Medicine, all in St. Louis, Missouri. That means physicians and pharmacists must rely on prescribing guides, such as the Beers criteria, which are based on consensus but lack supporting data. So as a “first step in addressing this lack of knowledge,” the researchers examined the long-term effects of the top 100 medications used by 4,414 participants in the National Alzheimer’s Coordinating Center database. They found that roughly 10% of those drugs were associated with long-term changes in cognition.

The researchers divided the patients into 4 groups: Group 1 was not taking the drug at visit 1 but was at visit 2; Group 2 stopped taking the drug between visit 1 and visit 2; Group 3 did not take the drug; and Group 4 was taking the drug at both visits. Composite scores were constructed from 10 psychometric tests. The researchers looked at change in cognition from the baseline visit to the follow-up visit, also looking for changes in or maintenance of the use of each medication. The average time between assessments was 1.2 years.

Nine drugs were associated with a statistically significant difference between at least 2 of the 4 study groups (P < .05). Naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline were all associated with improved psychometric performance. Bupropion, oxybutynin, and furosemide were associated with declines. Ferrous sulfate was associated with changes in attention, processing speed, and episodic memory, whereas the other 8 drugs were associated mainly with changes in attention and processing speed.

The drugs that improved cognition did so by a variety of proposed mechanisms. Naproxen may have improved scores by relieving pain, which can impede performance. Vitamin D deficiency is linked to reduced cognition in older adults, and ferrous sulfate is used to treat anemia; correcting those deficiencies may have helped cognition. Potassium chloride is used to treat or prevent hypokalemia, which can lead to confusion and cognitive problems; in this study, participants who stopped taking potassium showed drops in change scores compared with those who continued taking it.

Flax was an outlier in that the researchers were puzzled by its connection to better cognition. They did note, however, that people taking flax seed were also usually taking calcium-vitamin D. They hypothesize that people who take flax are likely to take other medicines or supplements that improve cognition. Sertraline has been shown to improve immediate and delayed verbal recall in older adults and to have a better effect on cognition than other selective serotonin reuptake inhibitors.

Some of their findings were new, the researchers say, such as the potential positive effects of ferrous sulfate. Similarly, bupropion has not previously been linked to negative effects on cognition in older adults. Such data deserve more examination, they say. Future studies may also show whether those drugs could delay the onset of incident dementia. 

Source
Obermann KR, Morris JC, Roe CM. Alzheimers Dement. 2013;9(6):724-732.
doi: 10.1016/j.jalz.2012.12.002.

There’s no gold standard list of drugs that affect cognition in cognitively normal older adults, say researchers from St. Louis College of Pharmacy, Knight Alzheimer’s Disease Research Center, and Washington University School of Medicine, all in St. Louis, Missouri. That means physicians and pharmacists must rely on prescribing guides, such as the Beers criteria, which are based on consensus but lack supporting data. So as a “first step in addressing this lack of knowledge,” the researchers examined the long-term effects of the top 100 medications used by 4,414 participants in the National Alzheimer’s Coordinating Center database. They found that roughly 10% of those drugs were associated with long-term changes in cognition.

The researchers divided the patients into 4 groups: Group 1 was not taking the drug at visit 1 but was at visit 2; Group 2 stopped taking the drug between visit 1 and visit 2; Group 3 did not take the drug; and Group 4 was taking the drug at both visits. Composite scores were constructed from 10 psychometric tests. The researchers looked at change in cognition from the baseline visit to the follow-up visit, also looking for changes in or maintenance of the use of each medication. The average time between assessments was 1.2 years.

Nine drugs were associated with a statistically significant difference between at least 2 of the 4 study groups (P < .05). Naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline were all associated with improved psychometric performance. Bupropion, oxybutynin, and furosemide were associated with declines. Ferrous sulfate was associated with changes in attention, processing speed, and episodic memory, whereas the other 8 drugs were associated mainly with changes in attention and processing speed.

The drugs that improved cognition did so by a variety of proposed mechanisms. Naproxen may have improved scores by relieving pain, which can impede performance. Vitamin D deficiency is linked to reduced cognition in older adults, and ferrous sulfate is used to treat anemia; correcting those deficiencies may have helped cognition. Potassium chloride is used to treat or prevent hypokalemia, which can lead to confusion and cognitive problems; in this study, participants who stopped taking potassium showed drops in change scores compared with those who continued taking it.

Flax was an outlier in that the researchers were puzzled by its connection to better cognition. They did note, however, that people taking flax seed were also usually taking calcium-vitamin D. They hypothesize that people who take flax are likely to take other medicines or supplements that improve cognition. Sertraline has been shown to improve immediate and delayed verbal recall in older adults and to have a better effect on cognition than other selective serotonin reuptake inhibitors.

Some of their findings were new, the researchers say, such as the potential positive effects of ferrous sulfate. Similarly, bupropion has not previously been linked to negative effects on cognition in older adults. Such data deserve more examination, they say. Future studies may also show whether those drugs could delay the onset of incident dementia. 

Source
Obermann KR, Morris JC, Roe CM. Alzheimers Dement. 2013;9(6):724-732.
doi: 10.1016/j.jalz.2012.12.002.

Lurasidone HCl tablets have been approved for adult patients with bipolar depression, both as monotherapy and as adjunctive therapy with lithium or valproate. The drug, an atypical antipsychotic, was already indicated for schizophrenia.

Lurasidone's efficacy was established in a 6-week monotherapy trial and a 6-week adjunctive therapy study with lithium or valproate.

In the multicenter monotherapy trial, 505 adult patients with major depressive episodes associated with bipolar I disorder were randomly assigned to 1 of 2 flexible-dose ranges of lurasidone (20-60 mg/d or 80-120 mg/d) or placebo. The mean daily dose was 31.8 mg in the 20- to 60-mg group and 82.0 mg in the higher dose group. In both dosage groups, nearly all patients were titrated to a higher dose during the study. Eight percent to 19% of patients in each of the 3 groups reported as-needed treatment with lorazepam or zolpidem.

Lurasidone was superior to placebo in reducing depressive symptoms and lowering disease-severity scores. There was a statistically significant reduction from baseline to week 6 in core depression symptoms for both dosages (P < .001), but the higher dose range did not provide additional efficacy. The proportion of patients in remission at endpoint was significantly greater in the 2 drug groups (42% and 40%), compared with patients on placebo (25%). Both dosages also significantly improved anxiety symptoms.

Lurasidone has been extensively studied for its use in treating schizophrenia; the monotherapy trial revealed no new safety concerns or risks, the  researchers say. Adverse events (AEs) were mostly mild or moderate. Researchers found a modest, dose-related increase in the frequency of nausea, sedation, vomiting, and extrapyramidal symptoms for the higher dose range. Similar numbers of patients withdrew from each group.

In a second multicenter double-blind study, 348 patients who were still symptomatic after treatment with lithium or valproate were randomly assigned to flexibly dosed lurasidone 20 mg/d to 120 mg/d or placebo. In this study, too, patients in the treatment groups showed significantly greater improvement in depressive symptoms, associated anxiety symptoms, and quality of life and functioning.

The researchers say this is, to their knowledge, the first large-scale, randomized, placebo-controlled trial to demonstrate efficacy of any medication adjunctive to mood stabilizers for the acute treatment of bipolar depression. “In particular,” they say, “no positive controlled studies have been published to date regarding the use of atypical antipsychotic medications as adjunctive therapy for patients with bipolar depression.”

Lurasidone’s effectiveness beyond 6 weeks has not been established in controlled studies. The manufacturer advises periodically reevaluating the long-term usefulness of the drug for the individual patient. As with other antidepressants, there is an increased risk of suicidal thoughts or actions. Lurasidone may cause serious AEs, including increased risk of death in elderly people who are confused or have memory loss. It is not intended for treatment of dementia-related psychosis.

Lurasidone is known to have a small dose-related effect on prolactin, as well as weight, lipids, and measures of glycemic control. However, it has appreciably fewer weight and metabolic effects, compared with other atypical antipsychotic agents, the researchers note. The metabolic profile of lurasidone in the adjunctive-therapy trial, the researchers say, suggests that it may be “associated with low cardiometabolic risk in this vulnerable clinical population.”

Sources
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):160-168.
doi: 10.1176/appi.ajp.2013.13070984.
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):169-177.
doi: 10.1176/appi.ajp.2013.13070985.

Lurasidone HCl tablets have been approved for adult patients with bipolar depression, both as monotherapy and as adjunctive therapy with lithium or valproate. The drug, an atypical antipsychotic, was already indicated for schizophrenia.

Lurasidone's efficacy was established in a 6-week monotherapy trial and a 6-week adjunctive therapy study with lithium or valproate.

In the multicenter monotherapy trial, 505 adult patients with major depressive episodes associated with bipolar I disorder were randomly assigned to 1 of 2 flexible-dose ranges of lurasidone (20-60 mg/d or 80-120 mg/d) or placebo. The mean daily dose was 31.8 mg in the 20- to 60-mg group and 82.0 mg in the higher dose group. In both dosage groups, nearly all patients were titrated to a higher dose during the study. Eight percent to 19% of patients in each of the 3 groups reported as-needed treatment with lorazepam or zolpidem.

Lurasidone was superior to placebo in reducing depressive symptoms and lowering disease-severity scores. There was a statistically significant reduction from baseline to week 6 in core depression symptoms for both dosages (P < .001), but the higher dose range did not provide additional efficacy. The proportion of patients in remission at endpoint was significantly greater in the 2 drug groups (42% and 40%), compared with patients on placebo (25%). Both dosages also significantly improved anxiety symptoms.

Lurasidone has been extensively studied for its use in treating schizophrenia; the monotherapy trial revealed no new safety concerns or risks, the  researchers say. Adverse events (AEs) were mostly mild or moderate. Researchers found a modest, dose-related increase in the frequency of nausea, sedation, vomiting, and extrapyramidal symptoms for the higher dose range. Similar numbers of patients withdrew from each group.

In a second multicenter double-blind study, 348 patients who were still symptomatic after treatment with lithium or valproate were randomly assigned to flexibly dosed lurasidone 20 mg/d to 120 mg/d or placebo. In this study, too, patients in the treatment groups showed significantly greater improvement in depressive symptoms, associated anxiety symptoms, and quality of life and functioning.

The researchers say this is, to their knowledge, the first large-scale, randomized, placebo-controlled trial to demonstrate efficacy of any medication adjunctive to mood stabilizers for the acute treatment of bipolar depression. “In particular,” they say, “no positive controlled studies have been published to date regarding the use of atypical antipsychotic medications as adjunctive therapy for patients with bipolar depression.”

Lurasidone’s effectiveness beyond 6 weeks has not been established in controlled studies. The manufacturer advises periodically reevaluating the long-term usefulness of the drug for the individual patient. As with other antidepressants, there is an increased risk of suicidal thoughts or actions. Lurasidone may cause serious AEs, including increased risk of death in elderly people who are confused or have memory loss. It is not intended for treatment of dementia-related psychosis.

Lurasidone is known to have a small dose-related effect on prolactin, as well as weight, lipids, and measures of glycemic control. However, it has appreciably fewer weight and metabolic effects, compared with other atypical antipsychotic agents, the researchers note. The metabolic profile of lurasidone in the adjunctive-therapy trial, the researchers say, suggests that it may be “associated with low cardiometabolic risk in this vulnerable clinical population.”

Sources
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):160-168.
doi: 10.1176/appi.ajp.2013.13070984.
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):169-177.
doi: 10.1176/appi.ajp.2013.13070985.

Lurasidone HCl tablets have been approved for adult patients with bipolar depression, both as monotherapy and as adjunctive therapy with lithium or valproate. The drug, an atypical antipsychotic, was already indicated for schizophrenia.

Lurasidone's efficacy was established in a 6-week monotherapy trial and a 6-week adjunctive therapy study with lithium or valproate.

In the multicenter monotherapy trial, 505 adult patients with major depressive episodes associated with bipolar I disorder were randomly assigned to 1 of 2 flexible-dose ranges of lurasidone (20-60 mg/d or 80-120 mg/d) or placebo. The mean daily dose was 31.8 mg in the 20- to 60-mg group and 82.0 mg in the higher dose group. In both dosage groups, nearly all patients were titrated to a higher dose during the study. Eight percent to 19% of patients in each of the 3 groups reported as-needed treatment with lorazepam or zolpidem.

Lurasidone was superior to placebo in reducing depressive symptoms and lowering disease-severity scores. There was a statistically significant reduction from baseline to week 6 in core depression symptoms for both dosages (P < .001), but the higher dose range did not provide additional efficacy. The proportion of patients in remission at endpoint was significantly greater in the 2 drug groups (42% and 40%), compared with patients on placebo (25%). Both dosages also significantly improved anxiety symptoms.

Lurasidone has been extensively studied for its use in treating schizophrenia; the monotherapy trial revealed no new safety concerns or risks, the  researchers say. Adverse events (AEs) were mostly mild or moderate. Researchers found a modest, dose-related increase in the frequency of nausea, sedation, vomiting, and extrapyramidal symptoms for the higher dose range. Similar numbers of patients withdrew from each group.

In a second multicenter double-blind study, 348 patients who were still symptomatic after treatment with lithium or valproate were randomly assigned to flexibly dosed lurasidone 20 mg/d to 120 mg/d or placebo. In this study, too, patients in the treatment groups showed significantly greater improvement in depressive symptoms, associated anxiety symptoms, and quality of life and functioning.

The researchers say this is, to their knowledge, the first large-scale, randomized, placebo-controlled trial to demonstrate efficacy of any medication adjunctive to mood stabilizers for the acute treatment of bipolar depression. “In particular,” they say, “no positive controlled studies have been published to date regarding the use of atypical antipsychotic medications as adjunctive therapy for patients with bipolar depression.”

Lurasidone’s effectiveness beyond 6 weeks has not been established in controlled studies. The manufacturer advises periodically reevaluating the long-term usefulness of the drug for the individual patient. As with other antidepressants, there is an increased risk of suicidal thoughts or actions. Lurasidone may cause serious AEs, including increased risk of death in elderly people who are confused or have memory loss. It is not intended for treatment of dementia-related psychosis.

Lurasidone is known to have a small dose-related effect on prolactin, as well as weight, lipids, and measures of glycemic control. However, it has appreciably fewer weight and metabolic effects, compared with other atypical antipsychotic agents, the researchers note. The metabolic profile of lurasidone in the adjunctive-therapy trial, the researchers say, suggests that it may be “associated with low cardiometabolic risk in this vulnerable clinical population.”

Sources
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):160-168.
doi: 10.1176/appi.ajp.2013.13070984.
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):169-177.
doi: 10.1176/appi.ajp.2013.13070985.