Mary Ann Moon

Adding telaprevir to standard peginterferon-plus-ribavirin therapy markedly improves the sustained virologic response in patients with chronic hepatitis C infection, even in those who did not respond well to a previous course of standard treatment, according to two separate phase III clinical trials reported in the June 23 New England Journal of Medicine.

The addition of the HCV protease inhibitor allowed most patients to halve their duration of therapy, reducing total treatment time from 48 to 24 weeks, minimizing the therapy’s toxic effects, and decreasing the rate of treatment discontinuation.

In the first report, Dr. Stefan Zeuzem and his associates in the REALIZE study group assessed the benefit of adding telaprevir to the regimens of 662 patients from 17 countries who had previously shown no response (28%), a partial response (19%), or a relapse (53%) after standard peginterferon-plus-ribavirin therapy.

They also assessed whether using a 4-week lead-in phase of peginterferon plus ribavirin before the addition of telaprevir would reduce the emergence of protease-resistant variants, as had been suggested by a previous study using a different HCV protease inhibitor.

The rates of sustained virologic response proved to be significantly higher in subjects who received telaprevir, both with and without the lead-in period, than in those who did not. These rates were 64% without a lead-in period and 66% with a lead-in period, compared with only 17% in the control group, which received peginterferon plus ribavirin only.

Even patients who had previously shown a minimal response to earlier therapy showed a nearly sixfold increase in sustained virologic response when telaprevir was added to the regimen, the investigators said (N. Engl. J. Med. 2011;364:2417-28).

Telaprevir improved the rates of sustained virologic response across all subgroups of patients, regardless of their viral load at baseline or the presence and severity of liver fibrosis or cirrhosis, said Dr. Zeuzem of Johann Wolfgang Goethe University Hospital, Frankfurt, Germany, and his colleagues.

Telaprevir also raised the rate of adverse events, chiefly fatigue, pruritus, rash, nausea, anemia, and diarrhea. The number of grade 3 adverse events (mainly anemia, neutropenia, and leucopenia) also was increased with telaprevir (37%), compared with the control group (22%). The rate of adverse events leading to permanent discontinuation of the study drugs was 13% in subjects who received telaprevir, compared with 3% in the control group.

In the second report, Dr. Ira M. Jacobson and his associates in the ADVANCE study assessed the addition of telaprevir in 1,088 patients at 123 international sites. These study subjects had never received therapy for chronic HCV.

The objective was to adjust treatment guided by the patient’s response after 4 weeks. Earlier studies have shown "high rates of early viral suppression and low rates of relapse after cessation of telaprevir therapy, [suggesting] that therapy could potentially be shortened to 24 weeks in patients who have a rapid virologic response – that is, patients in whom HCV RNA is undetectable at week 4 of treatment," said Dr. Jacobson of Cornell University and the Center for the Study of Hepatitis C, both in New York, and his colleagues.

One group of subjects received telaprevir in addition to standard peginterferon-plus-ribavirin therapy for 12 weeks. If they showed a rapid virologic response at 4 and 12 weeks, telaprevir was withdrawn and standard therapy was continued for 12 more weeks, for a total of 24 weeks of treatment. If there was no rapid response, standard therapy was extended for the customary 36 weeks, for a total of 48 weeks of treatment.

A second group received telaprevir plus standard therapy for 8 weeks, followed by placebo plus standard therapy for 4 weeks; their response to treatment determined the same two alternative courses of therapy as in group 1. The control group received placebo plus standard therapy for 12 weeks, followed by standard therapy for 36 weeks, for the standard total of 48 weeks of therapy.

A total of 75% of group 1 and 69% of group 2 showed a rapid and sustained virologic response, allowing them to complete treatment in half the usual time. Relapse was "infrequent" in these patients, indicating that a total of 24 weeks of therapy is sufficient for rapid responders, Dr. Jacobson and his colleagues said (N. Engl. J. Med. 2011;364:2405-16).

In comparison, only 44% of the control group achieved a rapid and sustained virologic response.

The addition of telaprevir also substantially improved treatment response among patient groups who usually respond poorly to standard therapy, including those with fibrosis or cirrhosis, older patients, diabetics, and those with a high viral load at baseline. Telaprevir more than doubled treatment response among black patients, who typically show a very poor response to interferon that likely results from genetic factors, the researchers noted.

Both studies were funded by Tibotec and Vertex Pharmaceuticals, which both manufacture telaprevir. Dr. Zeuzem and Dr. Jacobson reported ties to Tibotec and Vertex, as well as to numerous other industry sources.

Adding telaprevir to standard peginterferon-plus-ribavirin therapy markedly improves the sustained virologic response in patients with chronic hepatitis C infection, even in those who did not respond well to a previous course of standard treatment, according to two separate phase III clinical trials reported in the June 23 New England Journal of Medicine.

The addition of the HCV protease inhibitor allowed most patients to halve their duration of therapy, reducing total treatment time from 48 to 24 weeks, minimizing the therapy’s toxic effects, and decreasing the rate of treatment discontinuation.

In the first report, Dr. Stefan Zeuzem and his associates in the REALIZE study group assessed the benefit of adding telaprevir to the regimens of 662 patients from 17 countries who had previously shown no response (28%), a partial response (19%), or a relapse (53%) after standard peginterferon-plus-ribavirin therapy.

They also assessed whether using a 4-week lead-in phase of peginterferon plus ribavirin before the addition of telaprevir would reduce the emergence of protease-resistant variants, as had been suggested by a previous study using a different HCV protease inhibitor.

The rates of sustained virologic response proved to be significantly higher in subjects who received telaprevir, both with and without the lead-in period, than in those who did not. These rates were 64% without a lead-in period and 66% with a lead-in period, compared with only 17% in the control group, which received peginterferon plus ribavirin only.

Even patients who had previously shown a minimal response to earlier therapy showed a nearly sixfold increase in sustained virologic response when telaprevir was added to the regimen, the investigators said (N. Engl. J. Med. 2011;364:2417-28).

Telaprevir improved the rates of sustained virologic response across all subgroups of patients, regardless of their viral load at baseline or the presence and severity of liver fibrosis or cirrhosis, said Dr. Zeuzem of Johann Wolfgang Goethe University Hospital, Frankfurt, Germany, and his colleagues.

Telaprevir also raised the rate of adverse events, chiefly fatigue, pruritus, rash, nausea, anemia, and diarrhea. The number of grade 3 adverse events (mainly anemia, neutropenia, and leucopenia) also was increased with telaprevir (37%), compared with the control group (22%). The rate of adverse events leading to permanent discontinuation of the study drugs was 13% in subjects who received telaprevir, compared with 3% in the control group.

In the second report, Dr. Ira M. Jacobson and his associates in the ADVANCE study assessed the addition of telaprevir in 1,088 patients at 123 international sites. These study subjects had never received therapy for chronic HCV.

The objective was to adjust treatment guided by the patient’s response after 4 weeks. Earlier studies have shown "high rates of early viral suppression and low rates of relapse after cessation of telaprevir therapy, [suggesting] that therapy could potentially be shortened to 24 weeks in patients who have a rapid virologic response – that is, patients in whom HCV RNA is undetectable at week 4 of treatment," said Dr. Jacobson of Cornell University and the Center for the Study of Hepatitis C, both in New York, and his colleagues.

One group of subjects received telaprevir in addition to standard peginterferon-plus-ribavirin therapy for 12 weeks. If they showed a rapid virologic response at 4 and 12 weeks, telaprevir was withdrawn and standard therapy was continued for 12 more weeks, for a total of 24 weeks of treatment. If there was no rapid response, standard therapy was extended for the customary 36 weeks, for a total of 48 weeks of treatment.

A second group received telaprevir plus standard therapy for 8 weeks, followed by placebo plus standard therapy for 4 weeks; their response to treatment determined the same two alternative courses of therapy as in group 1. The control group received placebo plus standard therapy for 12 weeks, followed by standard therapy for 36 weeks, for the standard total of 48 weeks of therapy.

A total of 75% of group 1 and 69% of group 2 showed a rapid and sustained virologic response, allowing them to complete treatment in half the usual time. Relapse was "infrequent" in these patients, indicating that a total of 24 weeks of therapy is sufficient for rapid responders, Dr. Jacobson and his colleagues said (N. Engl. J. Med. 2011;364:2405-16).

In comparison, only 44% of the control group achieved a rapid and sustained virologic response.

The addition of telaprevir also substantially improved treatment response among patient groups who usually respond poorly to standard therapy, including those with fibrosis or cirrhosis, older patients, diabetics, and those with a high viral load at baseline. Telaprevir more than doubled treatment response among black patients, who typically show a very poor response to interferon that likely results from genetic factors, the researchers noted.

Both studies were funded by Tibotec and Vertex Pharmaceuticals, which both manufacture telaprevir. Dr. Zeuzem and Dr. Jacobson reported ties to Tibotec and Vertex, as well as to numerous other industry sources.

Adding telaprevir to standard peginterferon-plus-ribavirin therapy markedly improves the sustained virologic response in patients with chronic hepatitis C infection, even in those who did not respond well to a previous course of standard treatment, according to two separate phase III clinical trials reported in the June 23 New England Journal of Medicine.

The addition of the HCV protease inhibitor allowed most patients to halve their duration of therapy, reducing total treatment time from 48 to 24 weeks, minimizing the therapy’s toxic effects, and decreasing the rate of treatment discontinuation.

In the first report, Dr. Stefan Zeuzem and his associates in the REALIZE study group assessed the benefit of adding telaprevir to the regimens of 662 patients from 17 countries who had previously shown no response (28%), a partial response (19%), or a relapse (53%) after standard peginterferon-plus-ribavirin therapy.

They also assessed whether using a 4-week lead-in phase of peginterferon plus ribavirin before the addition of telaprevir would reduce the emergence of protease-resistant variants, as had been suggested by a previous study using a different HCV protease inhibitor.

The rates of sustained virologic response proved to be significantly higher in subjects who received telaprevir, both with and without the lead-in period, than in those who did not. These rates were 64% without a lead-in period and 66% with a lead-in period, compared with only 17% in the control group, which received peginterferon plus ribavirin only.

Even patients who had previously shown a minimal response to earlier therapy showed a nearly sixfold increase in sustained virologic response when telaprevir was added to the regimen, the investigators said (N. Engl. J. Med. 2011;364:2417-28).

Telaprevir improved the rates of sustained virologic response across all subgroups of patients, regardless of their viral load at baseline or the presence and severity of liver fibrosis or cirrhosis, said Dr. Zeuzem of Johann Wolfgang Goethe University Hospital, Frankfurt, Germany, and his colleagues.

Telaprevir also raised the rate of adverse events, chiefly fatigue, pruritus, rash, nausea, anemia, and diarrhea. The number of grade 3 adverse events (mainly anemia, neutropenia, and leucopenia) also was increased with telaprevir (37%), compared with the control group (22%). The rate of adverse events leading to permanent discontinuation of the study drugs was 13% in subjects who received telaprevir, compared with 3% in the control group.

In the second report, Dr. Ira M. Jacobson and his associates in the ADVANCE study assessed the addition of telaprevir in 1,088 patients at 123 international sites. These study subjects had never received therapy for chronic HCV.

The objective was to adjust treatment guided by the patient’s response after 4 weeks. Earlier studies have shown "high rates of early viral suppression and low rates of relapse after cessation of telaprevir therapy, [suggesting] that therapy could potentially be shortened to 24 weeks in patients who have a rapid virologic response – that is, patients in whom HCV RNA is undetectable at week 4 of treatment," said Dr. Jacobson of Cornell University and the Center for the Study of Hepatitis C, both in New York, and his colleagues.

One group of subjects received telaprevir in addition to standard peginterferon-plus-ribavirin therapy for 12 weeks. If they showed a rapid virologic response at 4 and 12 weeks, telaprevir was withdrawn and standard therapy was continued for 12 more weeks, for a total of 24 weeks of treatment. If there was no rapid response, standard therapy was extended for the customary 36 weeks, for a total of 48 weeks of treatment.

A second group received telaprevir plus standard therapy for 8 weeks, followed by placebo plus standard therapy for 4 weeks; their response to treatment determined the same two alternative courses of therapy as in group 1. The control group received placebo plus standard therapy for 12 weeks, followed by standard therapy for 36 weeks, for the standard total of 48 weeks of therapy.

A total of 75% of group 1 and 69% of group 2 showed a rapid and sustained virologic response, allowing them to complete treatment in half the usual time. Relapse was "infrequent" in these patients, indicating that a total of 24 weeks of therapy is sufficient for rapid responders, Dr. Jacobson and his colleagues said (N. Engl. J. Med. 2011;364:2405-16).

In comparison, only 44% of the control group achieved a rapid and sustained virologic response.

The addition of telaprevir also substantially improved treatment response among patient groups who usually respond poorly to standard therapy, including those with fibrosis or cirrhosis, older patients, diabetics, and those with a high viral load at baseline. Telaprevir more than doubled treatment response among black patients, who typically show a very poor response to interferon that likely results from genetic factors, the researchers noted.

Both studies were funded by Tibotec and Vertex Pharmaceuticals, which both manufacture telaprevir. Dr. Zeuzem and Dr. Jacobson reported ties to Tibotec and Vertex, as well as to numerous other industry sources.

Adding telaprevir to standard peginterferon-plus-ribavirin therapy markedly improves the sustained virologic response in patients with chronic hepatitis C infection, even in those who did not respond well to a previous course of standard treatment, according to two separate phase III clinical trials reported in the June 23 New England Journal of Medicine.

The addition of the HCV protease inhibitor allowed most patients to halve their duration of therapy, reducing total treatment time from 48 to 24 weeks, minimizing the therapy’s toxic effects, and decreasing the rate of treatment discontinuation.

In the first report, Dr. Stefan Zeuzem and his associates in the REALIZE study group assessed the benefit of adding telaprevir to the regimens of 662 patients from 17 countries who had previously shown no response (28%), a partial response (19%), or a relapse (53%) after standard peginterferon-plus-ribavirin therapy.

They also assessed whether using a 4-week lead-in phase of peginterferon plus ribavirin before the addition of telaprevir would reduce the emergence of protease-resistant variants, as had been suggested by a previous study using a different HCV protease inhibitor.

The rates of sustained virologic response proved to be significantly higher in subjects who received telaprevir, both with and without the lead-in period, than in those who did not. These rates were 64% without a lead-in period and 66% with a lead-in period, compared with only 17% in the control group, which received peginterferon plus ribavirin only.

Even patients who had previously shown a minimal response to earlier therapy showed a nearly sixfold increase in sustained virologic response when telaprevir was added to the regimen, the investigators said (N. Engl. J. Med. 2011;364:2417-28).

Telaprevir improved the rates of sustained virologic response across all subgroups of patients, regardless of their viral load at baseline or the presence and severity of liver fibrosis or cirrhosis, said Dr. Zeuzem of Johann Wolfgang Goethe University Hospital, Frankfurt, Germany, and his colleagues.

Telaprevir also raised the rate of adverse events, chiefly fatigue, pruritus, rash, nausea, anemia, and diarrhea. The number of grade 3 adverse events (mainly anemia, neutropenia, and leucopenia) also was increased with telaprevir (37%), compared with the control group (22%). The rate of adverse events leading to permanent discontinuation of the study drugs was 13% in subjects who received telaprevir, compared with 3% in the control group.

In the second report, Dr. Ira M. Jacobson and his associates in the ADVANCE study assessed the addition of telaprevir in 1,088 patients at 123 international sites. These study subjects had never received therapy for chronic HCV.

The objective was to adjust treatment guided by the patient’s response after 4 weeks. Earlier studies have shown "high rates of early viral suppression and low rates of relapse after cessation of telaprevir therapy, [suggesting] that therapy could potentially be shortened to 24 weeks in patients who have a rapid virologic response – that is, patients in whom HCV RNA is undetectable at week 4 of treatment," said Dr. Jacobson of Cornell University and the Center for the Study of Hepatitis C, both in New York, and his colleagues.

One group of subjects received telaprevir in addition to standard peginterferon-plus-ribavirin therapy for 12 weeks. If they showed a rapid virologic response at 4 and 12 weeks, telaprevir was withdrawn and standard therapy was continued for 12 more weeks, for a total of 24 weeks of treatment. If there was no rapid response, standard therapy was extended for the customary 36 weeks, for a total of 48 weeks of treatment.

A second group received telaprevir plus standard therapy for 8 weeks, followed by placebo plus standard therapy for 4 weeks; their response to treatment determined the same two alternative courses of therapy as in group 1. The control group received placebo plus standard therapy for 12 weeks, followed by standard therapy for 36 weeks, for the standard total of 48 weeks of therapy.

A total of 75% of group 1 and 69% of group 2 showed a rapid and sustained virologic response, allowing them to complete treatment in half the usual time. Relapse was "infrequent" in these patients, indicating that a total of 24 weeks of therapy is sufficient for rapid responders, Dr. Jacobson and his colleagues said (N. Engl. J. Med. 2011;364:2405-16).

In comparison, only 44% of the control group achieved a rapid and sustained virologic response.

The addition of telaprevir also substantially improved treatment response among patient groups who usually respond poorly to standard therapy, including those with fibrosis or cirrhosis, older patients, diabetics, and those with a high viral load at baseline. Telaprevir more than doubled treatment response among black patients, who typically show a very poor response to interferon that likely results from genetic factors, the researchers noted.

Both studies were funded by Tibotec and Vertex Pharmaceuticals, which both manufacture telaprevir. Dr. Zeuzem and Dr. Jacobson reported ties to Tibotec and Vertex, as well as to numerous other industry sources.

Adding telaprevir to standard peginterferon-plus-ribavirin therapy markedly improves the sustained virologic response in patients with chronic hepatitis C infection, even in those who did not respond well to a previous course of standard treatment, according to two separate phase III clinical trials reported in the June 23 New England Journal of Medicine.

The addition of the HCV protease inhibitor allowed most patients to halve their duration of therapy, reducing total treatment time from 48 to 24 weeks, minimizing the therapy’s toxic effects, and decreasing the rate of treatment discontinuation.

In the first report, Dr. Stefan Zeuzem and his associates in the REALIZE study group assessed the benefit of adding telaprevir to the regimens of 662 patients from 17 countries who had previously shown no response (28%), a partial response (19%), or a relapse (53%) after standard peginterferon-plus-ribavirin therapy.

They also assessed whether using a 4-week lead-in phase of peginterferon plus ribavirin before the addition of telaprevir would reduce the emergence of protease-resistant variants, as had been suggested by a previous study using a different HCV protease inhibitor.

The rates of sustained virologic response proved to be significantly higher in subjects who received telaprevir, both with and without the lead-in period, than in those who did not. These rates were 64% without a lead-in period and 66% with a lead-in period, compared with only 17% in the control group, which received peginterferon plus ribavirin only.

Even patients who had previously shown a minimal response to earlier therapy showed a nearly sixfold increase in sustained virologic response when telaprevir was added to the regimen, the investigators said (N. Engl. J. Med. 2011;364:2417-28).

Telaprevir improved the rates of sustained virologic response across all subgroups of patients, regardless of their viral load at baseline or the presence and severity of liver fibrosis or cirrhosis, said Dr. Zeuzem of Johann Wolfgang Goethe University Hospital, Frankfurt, Germany, and his colleagues.

Telaprevir also raised the rate of adverse events, chiefly fatigue, pruritus, rash, nausea, anemia, and diarrhea. The number of grade 3 adverse events (mainly anemia, neutropenia, and leucopenia) also was increased with telaprevir (37%), compared with the control group (22%). The rate of adverse events leading to permanent discontinuation of the study drugs was 13% in subjects who received telaprevir, compared with 3% in the control group.

In the second report, Dr. Ira M. Jacobson and his associates in the ADVANCE study assessed the addition of telaprevir in 1,088 patients at 123 international sites. These study subjects had never received therapy for chronic HCV.

The objective was to adjust treatment guided by the patient’s response after 4 weeks. Earlier studies have shown "high rates of early viral suppression and low rates of relapse after cessation of telaprevir therapy, [suggesting] that therapy could potentially be shortened to 24 weeks in patients who have a rapid virologic response – that is, patients in whom HCV RNA is undetectable at week 4 of treatment," said Dr. Jacobson of Cornell University and the Center for the Study of Hepatitis C, both in New York, and his colleagues.

One group of subjects received telaprevir in addition to standard peginterferon-plus-ribavirin therapy for 12 weeks. If they showed a rapid virologic response at 4 and 12 weeks, telaprevir was withdrawn and standard therapy was continued for 12 more weeks, for a total of 24 weeks of treatment. If there was no rapid response, standard therapy was extended for the customary 36 weeks, for a total of 48 weeks of treatment.

A second group received telaprevir plus standard therapy for 8 weeks, followed by placebo plus standard therapy for 4 weeks; their response to treatment determined the same two alternative courses of therapy as in group 1. The control group received placebo plus standard therapy for 12 weeks, followed by standard therapy for 36 weeks, for the standard total of 48 weeks of therapy.

A total of 75% of group 1 and 69% of group 2 showed a rapid and sustained virologic response, allowing them to complete treatment in half the usual time. Relapse was "infrequent" in these patients, indicating that a total of 24 weeks of therapy is sufficient for rapid responders, Dr. Jacobson and his colleagues said (N. Engl. J. Med. 2011;364:2405-16).

In comparison, only 44% of the control group achieved a rapid and sustained virologic response.

The addition of telaprevir also substantially improved treatment response among patient groups who usually respond poorly to standard therapy, including those with fibrosis or cirrhosis, older patients, diabetics, and those with a high viral load at baseline. Telaprevir more than doubled treatment response among black patients, who typically show a very poor response to interferon that likely results from genetic factors, the researchers noted.

Both studies were funded by Tibotec and Vertex Pharmaceuticals, which both manufacture telaprevir. Dr. Zeuzem and Dr. Jacobson reported ties to Tibotec and Vertex, as well as to numerous other industry sources.

Adding telaprevir to standard peginterferon-plus-ribavirin therapy markedly improves the sustained virologic response in patients with chronic hepatitis C infection, even in those who did not respond well to a previous course of standard treatment, according to two separate phase III clinical trials reported in the June 23 New England Journal of Medicine.

The addition of the HCV protease inhibitor allowed most patients to halve their duration of therapy, reducing total treatment time from 48 to 24 weeks, minimizing the therapy’s toxic effects, and decreasing the rate of treatment discontinuation.

In the first report, Dr. Stefan Zeuzem and his associates in the REALIZE study group assessed the benefit of adding telaprevir to the regimens of 662 patients from 17 countries who had previously shown no response (28%), a partial response (19%), or a relapse (53%) after standard peginterferon-plus-ribavirin therapy.

They also assessed whether using a 4-week lead-in phase of peginterferon plus ribavirin before the addition of telaprevir would reduce the emergence of protease-resistant variants, as had been suggested by a previous study using a different HCV protease inhibitor.

The rates of sustained virologic response proved to be significantly higher in subjects who received telaprevir, both with and without the lead-in period, than in those who did not. These rates were 64% without a lead-in period and 66% with a lead-in period, compared with only 17% in the control group, which received peginterferon plus ribavirin only.

Even patients who had previously shown a minimal response to earlier therapy showed a nearly sixfold increase in sustained virologic response when telaprevir was added to the regimen, the investigators said (N. Engl. J. Med. 2011;364:2417-28).

Telaprevir improved the rates of sustained virologic response across all subgroups of patients, regardless of their viral load at baseline or the presence and severity of liver fibrosis or cirrhosis, said Dr. Zeuzem of Johann Wolfgang Goethe University Hospital, Frankfurt, Germany, and his colleagues.

Telaprevir also raised the rate of adverse events, chiefly fatigue, pruritus, rash, nausea, anemia, and diarrhea. The number of grade 3 adverse events (mainly anemia, neutropenia, and leucopenia) also was increased with telaprevir (37%), compared with the control group (22%). The rate of adverse events leading to permanent discontinuation of the study drugs was 13% in subjects who received telaprevir, compared with 3% in the control group.

In the second report, Dr. Ira M. Jacobson and his associates in the ADVANCE study assessed the addition of telaprevir in 1,088 patients at 123 international sites. These study subjects had never received therapy for chronic HCV.

The objective was to adjust treatment guided by the patient’s response after 4 weeks. Earlier studies have shown "high rates of early viral suppression and low rates of relapse after cessation of telaprevir therapy, [suggesting] that therapy could potentially be shortened to 24 weeks in patients who have a rapid virologic response – that is, patients in whom HCV RNA is undetectable at week 4 of treatment," said Dr. Jacobson of Cornell University and the Center for the Study of Hepatitis C, both in New York, and his colleagues.

One group of subjects received telaprevir in addition to standard peginterferon-plus-ribavirin therapy for 12 weeks. If they showed a rapid virologic response at 4 and 12 weeks, telaprevir was withdrawn and standard therapy was continued for 12 more weeks, for a total of 24 weeks of treatment. If there was no rapid response, standard therapy was extended for the customary 36 weeks, for a total of 48 weeks of treatment.

A second group received telaprevir plus standard therapy for 8 weeks, followed by placebo plus standard therapy for 4 weeks; their response to treatment determined the same two alternative courses of therapy as in group 1. The control group received placebo plus standard therapy for 12 weeks, followed by standard therapy for 36 weeks, for the standard total of 48 weeks of therapy.

A total of 75% of group 1 and 69% of group 2 showed a rapid and sustained virologic response, allowing them to complete treatment in half the usual time. Relapse was "infrequent" in these patients, indicating that a total of 24 weeks of therapy is sufficient for rapid responders, Dr. Jacobson and his colleagues said (N. Engl. J. Med. 2011;364:2405-16).

In comparison, only 44% of the control group achieved a rapid and sustained virologic response.

The addition of telaprevir also substantially improved treatment response among patient groups who usually respond poorly to standard therapy, including those with fibrosis or cirrhosis, older patients, diabetics, and those with a high viral load at baseline. Telaprevir more than doubled treatment response among black patients, who typically show a very poor response to interferon that likely results from genetic factors, the researchers noted.

Both studies were funded by Tibotec and Vertex Pharmaceuticals, which both manufacture telaprevir. Dr. Zeuzem and Dr. Jacobson reported ties to Tibotec and Vertex, as well as to numerous other industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a report in the June 22/29 issue of JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes. They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a report in the June 22/29 issue of JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes. They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a report in the June 22/29 issue of JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes. They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a report in the June 22/29 issue of JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes. They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a report in the June 22/29 issue of JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes. They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a report in the June 22/29 issue of JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes. They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a new report in JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes.

They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a new report in JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes.

They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

Some disease-modifying antirheumatic drugs that are taken for rheumatoid arthritis or psoriasis appear to reduce the rate of incident diabetes, according to a new report in JAMA.

In a retrospective cohort study of patients who had RA or psoriasis, the use of a tumor necrosis factor (TNF) inhibitor or hydroxychloroquine to treat the systemic inflammatory disorder was associated with a reduced risk of developing diabetes, compared with the use of methotrexate or nonbiologic DMARDs, said Dr. Daniel H. Solomon of the divisions of pharmacoepidemiology and rheumatology at Brigham and Women’s Hospital, Boston, and his associates.

"Considering these results, in light of prior findings regarding improved insulin and glucose metabolism and reduced diabetes risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in diabetes prevention," they noted.

The investigators assessed the relationship between DMARDs and the risk of new-onset diabetes because previous studies have demonstrated that inflammatory conditions such as RA and psoriasis predispose patients to insulin resistance, and that some of these anti-inflammatory medications appear to improve insulin resistance and prevent the onset of diabetes.

They analyzed information from the databases of a Canadian health care system and a commercial U.S. health plan to identify 13,905 adults with RA or psoriasis who had filled at least one prescription for a DMARD and could be followed for approximately 6 months.

The DMARDs were divided into four mutually exclusive groups: TNF inhibitors such as adalimumab, etanercept, or infliximab; methotrexate; hydroxychloroquine; and other nonbiologic DMARDs such as sulfasalazine, leflunomide, cyclosporine, azathioprine, cyclophosphamide, mycophenolate mofetil, 6-thioguanine, acitretin, d-penicillamine, and the following gold preparations: auranofin, myochrysine, or solganol.

A total of 267 study subjects developed incident diabetes. The incidence was highest among patients who were taking nonbiologic DMARDs.

Patients taking a TNF inhibitor or hydroxychloroquine showed a reduced risk of diabetes, compared with patients taking any other agents. After accounting for the effects of potentially confounding factors such as patient age, sex, and several clinical variables, investigators found that the hazard ratios for diabetes were 0.62 for TNF inhibitors and 0.54 for hydroxychloroquine, compared with the nonbiologic DMARDs, Dr. Solomon and his colleagues said (JAMA 2011;305:2525-31).

"These findings held up across a variety of sensitivity analyses," they added.

"Taken in the context of prior research, [our] study supports the potential role for systemic immunosuppression in prevention and control of diabetes. If future studies show this convincingly, systemic immunosuppression in such situations would be predicated on a favorable risk-benefit profile."

For example, the benefit of immunosuppression may outweigh the risk in a patient with a systemic rheumatic disease for which a DMARD is already indicated. But immunosuppression may not outweigh the risk in a patient who already has diabetes and is prone to infection.

The investigators emphasized that this was an observational epidemiologic study without randomized-treatment assignment, so causation cannot be inferred. "It is possible that patients receiving a TNF inhibitor or hydroxychloroquine were different from the reference group of other nonbiologic DMARD users in ways that went unmeasured, such as body mass index, exercise participation, family history, or disease severity," they noted.

They added that the findings warrant confirmation in a randomized, controlled trial to test "the ability of these agents to prevent diabetes among participants with systemic inflammatory disorders."

This study was supported by Amgen. Dr. Solomon reported ties to Abbott, Amgen, Bristol-Myers Squibb, and Pfizer, and his associates reported ties to numerous industry sources.

The risk of developing type 2 diabetes rises with increasing doses of statin therapy, according to the findings of a large meta-analysis in the June 22/29 issue of JAMA.

"Our findings suggest that clinicians should be vigilant for the development of diabetes in patients receiving intensive statin therapy," said Dr. David Preiss of the BHF Glasgow (Scotland) Cardiovascular Research Centre at the University of Glasgow, and his associates.

Several recent studies have suggested that statin therapy may raise the risk of diabetes, and some have indicated that the risk is higher at higher doses of the drugs.

Dr. Preiss and his colleagues conducted a meta-analysis of five large (at least 1,000 subjects each) randomized clinical trials that compared moderate-dose with intensive-dose statin therapy and followed patients for a minimum of 1 year. These trials were intended to compare cardiovascular outcomes, but they also tracked adverse events, blood glucose levels, and the use of diabetes medications, so cases of new-onset diabetes could be identified.

Overall, 32,752 subjects who did not have diabetes at baseline were followed for a mean of 5 years. During that time 2,749 subjects (8%) developed diabetes.

There were 149 more cases of diabetes among subjects taking intensive statin therapy than in those taking moderate statin therapy, for an odds ratio of 1.1.

"In absolute terms, there were two additional cases of diabetes per 1,000 patient-years among those receiving intensive-dose therapy (mean 18.9 cases per 1,000 patient-years with high-dose statin treatment vs. 16.9 cases per 1,000 patient-years with moderate-dose therapy), corresponding to a number needed to harm of 498 per year," the investigators said.

This dose-response relationship persisted across several subgroups of patients, regardless of age, HDL cholesterol level, body mass index, and fasting plasma glucose level at baseline. The dose-response relationship also was comparable between subjects receiving simvastatin and those receiving atorvastatin, Dr. Preiss and his associates said (JAMA 2011;305:2556-64).

However, more intensive statin therapy also provided clear cardiovascular benefits compared with less intensive statin therapy. "When expressed in absolute terms, there was one additional case of diabetes for every 498 patients treated for 1 year, compared with one fewer patient experiencing a cardiovascular event for every 155 patients treated for 1 year," they noted.

"We hypothesize that given that cardiovascular risk from diabetes is modest in the first decade after diagnosis, and as the benefit of statin therapy increases over time and in absolute terms with increasing age, net cardiovascular benefit in high-risk individuals will still strongly favor statin therapy," the investigators said.

The mechanism by which statins raise diabetes risk is not known. The data on subgroups in this meta-analysis do not shed light on the issue since all subgroups were at comparable risk.

Future research should examine "the impact of statin therapy on glycemic control, and treatment requirements in patients with established diabetes," they added.

Dr. Preiss’s associates reported ties to numerous industry sources.

The risk of developing type 2 diabetes rises with increasing doses of statin therapy, according to the findings of a large meta-analysis in the June 22/29 issue of JAMA.

"Our findings suggest that clinicians should be vigilant for the development of diabetes in patients receiving intensive statin therapy," said Dr. David Preiss of the BHF Glasgow (Scotland) Cardiovascular Research Centre at the University of Glasgow, and his associates.

Several recent studies have suggested that statin therapy may raise the risk of diabetes, and some have indicated that the risk is higher at higher doses of the drugs.

Dr. Preiss and his colleagues conducted a meta-analysis of five large (at least 1,000 subjects each) randomized clinical trials that compared moderate-dose with intensive-dose statin therapy and followed patients for a minimum of 1 year. These trials were intended to compare cardiovascular outcomes, but they also tracked adverse events, blood glucose levels, and the use of diabetes medications, so cases of new-onset diabetes could be identified.

Overall, 32,752 subjects who did not have diabetes at baseline were followed for a mean of 5 years. During that time 2,749 subjects (8%) developed diabetes.

There were 149 more cases of diabetes among subjects taking intensive statin therapy than in those taking moderate statin therapy, for an odds ratio of 1.1.

"In absolute terms, there were two additional cases of diabetes per 1,000 patient-years among those receiving intensive-dose therapy (mean 18.9 cases per 1,000 patient-years with high-dose statin treatment vs. 16.9 cases per 1,000 patient-years with moderate-dose therapy), corresponding to a number needed to harm of 498 per year," the investigators said.

This dose-response relationship persisted across several subgroups of patients, regardless of age, HDL cholesterol level, body mass index, and fasting plasma glucose level at baseline. The dose-response relationship also was comparable between subjects receiving simvastatin and those receiving atorvastatin, Dr. Preiss and his associates said (JAMA 2011;305:2556-64).

However, more intensive statin therapy also provided clear cardiovascular benefits compared with less intensive statin therapy. "When expressed in absolute terms, there was one additional case of diabetes for every 498 patients treated for 1 year, compared with one fewer patient experiencing a cardiovascular event for every 155 patients treated for 1 year," they noted.

"We hypothesize that given that cardiovascular risk from diabetes is modest in the first decade after diagnosis, and as the benefit of statin therapy increases over time and in absolute terms with increasing age, net cardiovascular benefit in high-risk individuals will still strongly favor statin therapy," the investigators said.

The mechanism by which statins raise diabetes risk is not known. The data on subgroups in this meta-analysis do not shed light on the issue since all subgroups were at comparable risk.

Future research should examine "the impact of statin therapy on glycemic control, and treatment requirements in patients with established diabetes," they added.

Dr. Preiss’s associates reported ties to numerous industry sources.

The risk of developing type 2 diabetes rises with increasing doses of statin therapy, according to the findings of a large meta-analysis in the June 22/29 issue of JAMA.

"Our findings suggest that clinicians should be vigilant for the development of diabetes in patients receiving intensive statin therapy," said Dr. David Preiss of the BHF Glasgow (Scotland) Cardiovascular Research Centre at the University of Glasgow, and his associates.

Several recent studies have suggested that statin therapy may raise the risk of diabetes, and some have indicated that the risk is higher at higher doses of the drugs.

Dr. Preiss and his colleagues conducted a meta-analysis of five large (at least 1,000 subjects each) randomized clinical trials that compared moderate-dose with intensive-dose statin therapy and followed patients for a minimum of 1 year. These trials were intended to compare cardiovascular outcomes, but they also tracked adverse events, blood glucose levels, and the use of diabetes medications, so cases of new-onset diabetes could be identified.

Overall, 32,752 subjects who did not have diabetes at baseline were followed for a mean of 5 years. During that time 2,749 subjects (8%) developed diabetes.

There were 149 more cases of diabetes among subjects taking intensive statin therapy than in those taking moderate statin therapy, for an odds ratio of 1.1.

"In absolute terms, there were two additional cases of diabetes per 1,000 patient-years among those receiving intensive-dose therapy (mean 18.9 cases per 1,000 patient-years with high-dose statin treatment vs. 16.9 cases per 1,000 patient-years with moderate-dose therapy), corresponding to a number needed to harm of 498 per year," the investigators said.

This dose-response relationship persisted across several subgroups of patients, regardless of age, HDL cholesterol level, body mass index, and fasting plasma glucose level at baseline. The dose-response relationship also was comparable between subjects receiving simvastatin and those receiving atorvastatin, Dr. Preiss and his associates said (JAMA 2011;305:2556-64).

However, more intensive statin therapy also provided clear cardiovascular benefits compared with less intensive statin therapy. "When expressed in absolute terms, there was one additional case of diabetes for every 498 patients treated for 1 year, compared with one fewer patient experiencing a cardiovascular event for every 155 patients treated for 1 year," they noted.

"We hypothesize that given that cardiovascular risk from diabetes is modest in the first decade after diagnosis, and as the benefit of statin therapy increases over time and in absolute terms with increasing age, net cardiovascular benefit in high-risk individuals will still strongly favor statin therapy," the investigators said.

The mechanism by which statins raise diabetes risk is not known. The data on subgroups in this meta-analysis do not shed light on the issue since all subgroups were at comparable risk.

Future research should examine "the impact of statin therapy on glycemic control, and treatment requirements in patients with established diabetes," they added.

Dr. Preiss’s associates reported ties to numerous industry sources.

The risk of developing type 2 diabetes rises with increasing doses of statin therapy, according to the findings of a large meta-analysis in the June 22/29 issue of JAMA.

"Our findings suggest that clinicians should be vigilant for the development of diabetes in patients receiving intensive statin therapy," said Dr. David Preiss of the BHF Glasgow (Scotland) Cardiovascular Research Centre at the University of Glasgow, and his associates.

Several recent studies have suggested that statin therapy may raise the risk of diabetes, and some have indicated that the risk is higher at higher doses of the drugs.

Dr. Preiss and his colleagues conducted a meta-analysis of five large (at least 1,000 subjects each) randomized clinical trials that compared moderate-dose with intensive-dose statin therapy and followed patients for a minimum of 1 year. These trials were intended to compare cardiovascular outcomes, but they also tracked adverse events, blood glucose levels, and the use of diabetes medications, so cases of new-onset diabetes could be identified.

Overall, 32,752 subjects who did not have diabetes at baseline were followed for a mean of 5 years. During that time 2,749 subjects (8%) developed diabetes.

There were 149 more cases of diabetes among subjects taking intensive statin therapy than in those taking moderate statin therapy, for an odds ratio of 1.1.

"In absolute terms, there were two additional cases of diabetes per 1,000 patient-years among those receiving intensive-dose therapy (mean 18.9 cases per 1,000 patient-years with high-dose statin treatment vs. 16.9 cases per 1,000 patient-years with moderate-dose therapy), corresponding to a number needed to harm of 498 per year," the investigators said.

This dose-response relationship persisted across several subgroups of patients, regardless of age, HDL cholesterol level, body mass index, and fasting plasma glucose level at baseline. The dose-response relationship also was comparable between subjects receiving simvastatin and those receiving atorvastatin, Dr. Preiss and his associates said (JAMA 2011;305:2556-64).

However, more intensive statin therapy also provided clear cardiovascular benefits compared with less intensive statin therapy. "When expressed in absolute terms, there was one additional case of diabetes for every 498 patients treated for 1 year, compared with one fewer patient experiencing a cardiovascular event for every 155 patients treated for 1 year," they noted.

"We hypothesize that given that cardiovascular risk from diabetes is modest in the first decade after diagnosis, and as the benefit of statin therapy increases over time and in absolute terms with increasing age, net cardiovascular benefit in high-risk individuals will still strongly favor statin therapy," the investigators said.

The mechanism by which statins raise diabetes risk is not known. The data on subgroups in this meta-analysis do not shed light on the issue since all subgroups were at comparable risk.

Future research should examine "the impact of statin therapy on glycemic control, and treatment requirements in patients with established diabetes," they added.

Dr. Preiss’s associates reported ties to numerous industry sources.

The risk of developing type 2 diabetes rises with increasing doses of statin therapy, according to the findings of a large meta-analysis in the June 22/29 issue of JAMA.

"Our findings suggest that clinicians should be vigilant for the development of diabetes in patients receiving intensive statin therapy," said Dr. David Preiss of the BHF Glasgow (Scotland) Cardiovascular Research Centre at the University of Glasgow, and his associates.

Several recent studies have suggested that statin therapy may raise the risk of diabetes, and some have indicated that the risk is higher at higher doses of the drugs.

Dr. Preiss and his colleagues conducted a meta-analysis of five large (at least 1,000 subjects each) randomized clinical trials that compared moderate-dose with intensive-dose statin therapy and followed patients for a minimum of 1 year. These trials were intended to compare cardiovascular outcomes, but they also tracked adverse events, blood glucose levels, and the use of diabetes medications, so cases of new-onset diabetes could be identified.

Overall, 32,752 subjects who did not have diabetes at baseline were followed for a mean of 5 years. During that time 2,749 subjects (8%) developed diabetes.

There were 149 more cases of diabetes among subjects taking intensive statin therapy than in those taking moderate statin therapy, for an odds ratio of 1.1.

"In absolute terms, there were two additional cases of diabetes per 1,000 patient-years among those receiving intensive-dose therapy (mean 18.9 cases per 1,000 patient-years with high-dose statin treatment vs. 16.9 cases per 1,000 patient-years with moderate-dose therapy), corresponding to a number needed to harm of 498 per year," the investigators said.

This dose-response relationship persisted across several subgroups of patients, regardless of age, HDL cholesterol level, body mass index, and fasting plasma glucose level at baseline. The dose-response relationship also was comparable between subjects receiving simvastatin and those receiving atorvastatin, Dr. Preiss and his associates said (JAMA 2011;305:2556-64).

However, more intensive statin therapy also provided clear cardiovascular benefits compared with less intensive statin therapy. "When expressed in absolute terms, there was one additional case of diabetes for every 498 patients treated for 1 year, compared with one fewer patient experiencing a cardiovascular event for every 155 patients treated for 1 year," they noted.

"We hypothesize that given that cardiovascular risk from diabetes is modest in the first decade after diagnosis, and as the benefit of statin therapy increases over time and in absolute terms with increasing age, net cardiovascular benefit in high-risk individuals will still strongly favor statin therapy," the investigators said.

The mechanism by which statins raise diabetes risk is not known. The data on subgroups in this meta-analysis do not shed light on the issue since all subgroups were at comparable risk.

Future research should examine "the impact of statin therapy on glycemic control, and treatment requirements in patients with established diabetes," they added.

Dr. Preiss’s associates reported ties to numerous industry sources.

The risk of developing type 2 diabetes rises with increasing doses of statin therapy, according to the findings of a large meta-analysis in the June 22/29 issue of JAMA.

"Our findings suggest that clinicians should be vigilant for the development of diabetes in patients receiving intensive statin therapy," said Dr. David Preiss of the BHF Glasgow (Scotland) Cardiovascular Research Centre at the University of Glasgow, and his associates.

Several recent studies have suggested that statin therapy may raise the risk of diabetes, and some have indicated that the risk is higher at higher doses of the drugs.

Dr. Preiss and his colleagues conducted a meta-analysis of five large (at least 1,000 subjects each) randomized clinical trials that compared moderate-dose with intensive-dose statin therapy and followed patients for a minimum of 1 year. These trials were intended to compare cardiovascular outcomes, but they also tracked adverse events, blood glucose levels, and the use of diabetes medications, so cases of new-onset diabetes could be identified.

Overall, 32,752 subjects who did not have diabetes at baseline were followed for a mean of 5 years. During that time 2,749 subjects (8%) developed diabetes.

There were 149 more cases of diabetes among subjects taking intensive statin therapy than in those taking moderate statin therapy, for an odds ratio of 1.1.

"In absolute terms, there were two additional cases of diabetes per 1,000 patient-years among those receiving intensive-dose therapy (mean 18.9 cases per 1,000 patient-years with high-dose statin treatment vs. 16.9 cases per 1,000 patient-years with moderate-dose therapy), corresponding to a number needed to harm of 498 per year," the investigators said.

This dose-response relationship persisted across several subgroups of patients, regardless of age, HDL cholesterol level, body mass index, and fasting plasma glucose level at baseline. The dose-response relationship also was comparable between subjects receiving simvastatin and those receiving atorvastatin, Dr. Preiss and his associates said (JAMA 2011;305:2556-64).

However, more intensive statin therapy also provided clear cardiovascular benefits compared with less intensive statin therapy. "When expressed in absolute terms, there was one additional case of diabetes for every 498 patients treated for 1 year, compared with one fewer patient experiencing a cardiovascular event for every 155 patients treated for 1 year," they noted.

"We hypothesize that given that cardiovascular risk from diabetes is modest in the first decade after diagnosis, and as the benefit of statin therapy increases over time and in absolute terms with increasing age, net cardiovascular benefit in high-risk individuals will still strongly favor statin therapy," the investigators said.

The mechanism by which statins raise diabetes risk is not known. The data on subgroups in this meta-analysis do not shed light on the issue since all subgroups were at comparable risk.

Future research should examine "the impact of statin therapy on glycemic control, and treatment requirements in patients with established diabetes," they added.

Dr. Preiss’s associates reported ties to numerous industry sources.

The second-generation rotavirus vaccine appears to raise the risk of intussusception in a similar manner as its predecessor, but its benefits still far outweigh that risk, according to a report in the June 16 issue of the New England Journal of Medicine. 

Case series and case-control analyses of immunization data from Mexico and Brazil indicate that the short-term risk of intussusception is approximately 1 in every 51,000-68,000 infants receiving the rotavirus vaccine (RV1, Rotarix), which translates to an annual "excess of 96 hospitalizations ... and 5 deaths in the two countries combined." This risk is far exceeded by "the real-world benefits of RV1 vaccination, which has annually prevented more than 80,000 hospitalizations and 1,300 deaths in Mexico and Brazil," said Dr. Manish M. Patel of the Centers for Disease Control and Prevention, Atlanta, and his associates.

"These emerging data on safety and benefits have been reviewed by the World Health Organization as well as by regulatory agencies and immunization advisory committees in Brazil, Mexico, and the United States. ... [T]hese groups unanimously favored continuing the recommendation that rotavirus vaccination be administered to infants to prevent severe and potentially fatal rotavirus disease," the investigators noted (N. Engl. J. Med. 2011;364:2283-92).

They undertook this study because, after Brazil and Mexico added RV1 to their national childhood immunization programs in 2007, "the combined annual birth cohort of approximately 6 million in these two countries provided an opportunity to assess whether routine vaccination with RV1 was associated with intussusception," Dr. Patel and his colleagues wrote.

Using hospital records, they identified 615 infants who developed intussusception (285 in Mexico and 330 in Brazil) and matched them with 2,050 control infants (739 in Mexico and 1,311 in Brazil). Of these, 594 case patients (97%) and 2,033 controls (99%) had a history of vaccination confirmed by a vaccination card.

In Mexico, intussusception was significantly more likely to develop in the first week after the first dose of the vaccine than during other periods, with an incidence ratio of 5.3.

"This corresponds to the dose and period in which there is peak intestinal replication of vaccine virus and in which a local inflammatory response in the lymphatic tissue or intestines may occur – a response that has been implicated in the pathogenesis of intussusception," the investigators said.

In contrast, "neither a clustering of cases after the first dose nor a risk of the magnitude noted in Mexico was observed in Brazil. However, a small but significantly elevated rate was noted 1-7 days after the second dose," they said.

This absence of risk with the first RV1 dose was at first "perplexing." However, RV1 is administered together with oral poliovirus vaccine in Brazil but with inactivated poliovirus vaccine in Mexico. The first dose of oral polio vaccine is known to decrease the immunogenicity of RV1 when the two are given together, which may in turn reduce the risk of RV1-associated intussusception.

"Other factors, such as differences in the diets of the infants, breastfeeding practices, the natural risk of intussusception, and maternal antibody levels, might also have contributed to the variation in risk between Mexico and Brazil," Dr. Patel and his associates wrote.

"Our benefit-risk analysis indicated that an RV1 vaccination program would avert 663 deaths and 11,551 hospitalizations due to rotavirus disease in Mexico and 640 deaths and 69,572 hospitalizations in Brazil among children younger than 5 years of age.

"In contrast, we predict that a vaccination program would cause 41 excess hospitalizations (approximately 1 per 51,000 vaccinated infants) and 2 deaths due to intussusception in Mexico and 55 excess hospitalizations (approximately 1 per 68,000 vaccinated infants) and 3 deaths in Brazil," the researchers said.

They emphasized that the experience in Mexico may not apply to developing countries, most of which use the oral poliovirus vaccine. In addition, the immune response to rotavirus vaccination, as well as fecal shedding of vaccine strains of the virus, are generally lower in developing than in industrialized countries, which may indicate a difference in intussusception risk.

This study was funded in part by the GAVI Alliance under a collaborative agreement with the Program for Appropriate Technology in Health (PATH) and in part by the U.S. Department of Health and Human Services. Rotarix is a product of GlaxoSmithKline. Dr. Patel and his coinvestigators reported no relevant financial disclosures.

The second-generation rotavirus vaccine appears to raise the risk of intussusception in a similar manner as its predecessor, but its benefits still far outweigh that risk, according to a report in the June 16 issue of the New England Journal of Medicine. 

Case series and case-control analyses of immunization data from Mexico and Brazil indicate that the short-term risk of intussusception is approximately 1 in every 51,000-68,000 infants receiving the rotavirus vaccine (RV1, Rotarix), which translates to an annual "excess of 96 hospitalizations ... and 5 deaths in the two countries combined." This risk is far exceeded by "the real-world benefits of RV1 vaccination, which has annually prevented more than 80,000 hospitalizations and 1,300 deaths in Mexico and Brazil," said Dr. Manish M. Patel of the Centers for Disease Control and Prevention, Atlanta, and his associates.

"These emerging data on safety and benefits have been reviewed by the World Health Organization as well as by regulatory agencies and immunization advisory committees in Brazil, Mexico, and the United States. ... [T]hese groups unanimously favored continuing the recommendation that rotavirus vaccination be administered to infants to prevent severe and potentially fatal rotavirus disease," the investigators noted (N. Engl. J. Med. 2011;364:2283-92).

They undertook this study because, after Brazil and Mexico added RV1 to their national childhood immunization programs in 2007, "the combined annual birth cohort of approximately 6 million in these two countries provided an opportunity to assess whether routine vaccination with RV1 was associated with intussusception," Dr. Patel and his colleagues wrote.

Using hospital records, they identified 615 infants who developed intussusception (285 in Mexico and 330 in Brazil) and matched them with 2,050 control infants (739 in Mexico and 1,311 in Brazil). Of these, 594 case patients (97%) and 2,033 controls (99%) had a history of vaccination confirmed by a vaccination card.

In Mexico, intussusception was significantly more likely to develop in the first week after the first dose of the vaccine than during other periods, with an incidence ratio of 5.3.

"This corresponds to the dose and period in which there is peak intestinal replication of vaccine virus and in which a local inflammatory response in the lymphatic tissue or intestines may occur – a response that has been implicated in the pathogenesis of intussusception," the investigators said.

In contrast, "neither a clustering of cases after the first dose nor a risk of the magnitude noted in Mexico was observed in Brazil. However, a small but significantly elevated rate was noted 1-7 days after the second dose," they said.

This absence of risk with the first RV1 dose was at first "perplexing." However, RV1 is administered together with oral poliovirus vaccine in Brazil but with inactivated poliovirus vaccine in Mexico. The first dose of oral polio vaccine is known to decrease the immunogenicity of RV1 when the two are given together, which may in turn reduce the risk of RV1-associated intussusception.

"Other factors, such as differences in the diets of the infants, breastfeeding practices, the natural risk of intussusception, and maternal antibody levels, might also have contributed to the variation in risk between Mexico and Brazil," Dr. Patel and his associates wrote.

"Our benefit-risk analysis indicated that an RV1 vaccination program would avert 663 deaths and 11,551 hospitalizations due to rotavirus disease in Mexico and 640 deaths and 69,572 hospitalizations in Brazil among children younger than 5 years of age.

"In contrast, we predict that a vaccination program would cause 41 excess hospitalizations (approximately 1 per 51,000 vaccinated infants) and 2 deaths due to intussusception in Mexico and 55 excess hospitalizations (approximately 1 per 68,000 vaccinated infants) and 3 deaths in Brazil," the researchers said.

They emphasized that the experience in Mexico may not apply to developing countries, most of which use the oral poliovirus vaccine. In addition, the immune response to rotavirus vaccination, as well as fecal shedding of vaccine strains of the virus, are generally lower in developing than in industrialized countries, which may indicate a difference in intussusception risk.

This study was funded in part by the GAVI Alliance under a collaborative agreement with the Program for Appropriate Technology in Health (PATH) and in part by the U.S. Department of Health and Human Services. Rotarix is a product of GlaxoSmithKline. Dr. Patel and his coinvestigators reported no relevant financial disclosures.

The second-generation rotavirus vaccine appears to raise the risk of intussusception in a similar manner as its predecessor, but its benefits still far outweigh that risk, according to a report in the June 16 issue of the New England Journal of Medicine. 

Case series and case-control analyses of immunization data from Mexico and Brazil indicate that the short-term risk of intussusception is approximately 1 in every 51,000-68,000 infants receiving the rotavirus vaccine (RV1, Rotarix), which translates to an annual "excess of 96 hospitalizations ... and 5 deaths in the two countries combined." This risk is far exceeded by "the real-world benefits of RV1 vaccination, which has annually prevented more than 80,000 hospitalizations and 1,300 deaths in Mexico and Brazil," said Dr. Manish M. Patel of the Centers for Disease Control and Prevention, Atlanta, and his associates.

"These emerging data on safety and benefits have been reviewed by the World Health Organization as well as by regulatory agencies and immunization advisory committees in Brazil, Mexico, and the United States. ... [T]hese groups unanimously favored continuing the recommendation that rotavirus vaccination be administered to infants to prevent severe and potentially fatal rotavirus disease," the investigators noted (N. Engl. J. Med. 2011;364:2283-92).

They undertook this study because, after Brazil and Mexico added RV1 to their national childhood immunization programs in 2007, "the combined annual birth cohort of approximately 6 million in these two countries provided an opportunity to assess whether routine vaccination with RV1 was associated with intussusception," Dr. Patel and his colleagues wrote.

Using hospital records, they identified 615 infants who developed intussusception (285 in Mexico and 330 in Brazil) and matched them with 2,050 control infants (739 in Mexico and 1,311 in Brazil). Of these, 594 case patients (97%) and 2,033 controls (99%) had a history of vaccination confirmed by a vaccination card.

In Mexico, intussusception was significantly more likely to develop in the first week after the first dose of the vaccine than during other periods, with an incidence ratio of 5.3.

"This corresponds to the dose and period in which there is peak intestinal replication of vaccine virus and in which a local inflammatory response in the lymphatic tissue or intestines may occur – a response that has been implicated in the pathogenesis of intussusception," the investigators said.

In contrast, "neither a clustering of cases after the first dose nor a risk of the magnitude noted in Mexico was observed in Brazil. However, a small but significantly elevated rate was noted 1-7 days after the second dose," they said.

This absence of risk with the first RV1 dose was at first "perplexing." However, RV1 is administered together with oral poliovirus vaccine in Brazil but with inactivated poliovirus vaccine in Mexico. The first dose of oral polio vaccine is known to decrease the immunogenicity of RV1 when the two are given together, which may in turn reduce the risk of RV1-associated intussusception.

"Other factors, such as differences in the diets of the infants, breastfeeding practices, the natural risk of intussusception, and maternal antibody levels, might also have contributed to the variation in risk between Mexico and Brazil," Dr. Patel and his associates wrote.

"Our benefit-risk analysis indicated that an RV1 vaccination program would avert 663 deaths and 11,551 hospitalizations due to rotavirus disease in Mexico and 640 deaths and 69,572 hospitalizations in Brazil among children younger than 5 years of age.

"In contrast, we predict that a vaccination program would cause 41 excess hospitalizations (approximately 1 per 51,000 vaccinated infants) and 2 deaths due to intussusception in Mexico and 55 excess hospitalizations (approximately 1 per 68,000 vaccinated infants) and 3 deaths in Brazil," the researchers said.

They emphasized that the experience in Mexico may not apply to developing countries, most of which use the oral poliovirus vaccine. In addition, the immune response to rotavirus vaccination, as well as fecal shedding of vaccine strains of the virus, are generally lower in developing than in industrialized countries, which may indicate a difference in intussusception risk.

This study was funded in part by the GAVI Alliance under a collaborative agreement with the Program for Appropriate Technology in Health (PATH) and in part by the U.S. Department of Health and Human Services. Rotarix is a product of GlaxoSmithKline. Dr. Patel and his coinvestigators reported no relevant financial disclosures.

The second-generation rotavirus vaccine appears to raise the risk of intussusception in a similar manner as its predecessor, but its benefits still far outweigh that risk, according to a report in the June 16 issue of the New England Journal of Medicine. 

Case series and case-control analyses of immunization data from Mexico and Brazil indicate that the short-term risk of intussusception is approximately 1 in every 51,000-68,000 infants receiving the rotavirus vaccine (RV1, Rotarix), which translates to an annual "excess of 96 hospitalizations ... and 5 deaths in the two countries combined." This risk is far exceeded by "the real-world benefits of RV1 vaccination, which has annually prevented more than 80,000 hospitalizations and 1,300 deaths in Mexico and Brazil," said Dr. Manish M. Patel of the Centers for Disease Control and Prevention, Atlanta, and his associates.

"These emerging data on safety and benefits have been reviewed by the World Health Organization as well as by regulatory agencies and immunization advisory committees in Brazil, Mexico, and the United States. ... [T]hese groups unanimously favored continuing the recommendation that rotavirus vaccination be administered to infants to prevent severe and potentially fatal rotavirus disease," the investigators noted (N. Engl. J. Med. 2011;364:2283-92).

They undertook this study because, after Brazil and Mexico added RV1 to their national childhood immunization programs in 2007, "the combined annual birth cohort of approximately 6 million in these two countries provided an opportunity to assess whether routine vaccination with RV1 was associated with intussusception," Dr. Patel and his colleagues wrote.

Using hospital records, they identified 615 infants who developed intussusception (285 in Mexico and 330 in Brazil) and matched them with 2,050 control infants (739 in Mexico and 1,311 in Brazil). Of these, 594 case patients (97%) and 2,033 controls (99%) had a history of vaccination confirmed by a vaccination card.

In Mexico, intussusception was significantly more likely to develop in the first week after the first dose of the vaccine than during other periods, with an incidence ratio of 5.3.

"This corresponds to the dose and period in which there is peak intestinal replication of vaccine virus and in which a local inflammatory response in the lymphatic tissue or intestines may occur – a response that has been implicated in the pathogenesis of intussusception," the investigators said.

In contrast, "neither a clustering of cases after the first dose nor a risk of the magnitude noted in Mexico was observed in Brazil. However, a small but significantly elevated rate was noted 1-7 days after the second dose," they said.

This absence of risk with the first RV1 dose was at first "perplexing." However, RV1 is administered together with oral poliovirus vaccine in Brazil but with inactivated poliovirus vaccine in Mexico. The first dose of oral polio vaccine is known to decrease the immunogenicity of RV1 when the two are given together, which may in turn reduce the risk of RV1-associated intussusception.

"Other factors, such as differences in the diets of the infants, breastfeeding practices, the natural risk of intussusception, and maternal antibody levels, might also have contributed to the variation in risk between Mexico and Brazil," Dr. Patel and his associates wrote.

"Our benefit-risk analysis indicated that an RV1 vaccination program would avert 663 deaths and 11,551 hospitalizations due to rotavirus disease in Mexico and 640 deaths and 69,572 hospitalizations in Brazil among children younger than 5 years of age.

"In contrast, we predict that a vaccination program would cause 41 excess hospitalizations (approximately 1 per 51,000 vaccinated infants) and 2 deaths due to intussusception in Mexico and 55 excess hospitalizations (approximately 1 per 68,000 vaccinated infants) and 3 deaths in Brazil," the researchers said.

They emphasized that the experience in Mexico may not apply to developing countries, most of which use the oral poliovirus vaccine. In addition, the immune response to rotavirus vaccination, as well as fecal shedding of vaccine strains of the virus, are generally lower in developing than in industrialized countries, which may indicate a difference in intussusception risk.

This study was funded in part by the GAVI Alliance under a collaborative agreement with the Program for Appropriate Technology in Health (PATH) and in part by the U.S. Department of Health and Human Services. Rotarix is a product of GlaxoSmithKline. Dr. Patel and his coinvestigators reported no relevant financial disclosures.

The second-generation rotavirus vaccine appears to raise the risk of intussusception in a similar manner as its predecessor, but its benefits still far outweigh that risk, according to a report in the June 16 issue of the New England Journal of Medicine. 

Case series and case-control analyses of immunization data from Mexico and Brazil indicate that the short-term risk of intussusception is approximately 1 in every 51,000-68,000 infants receiving the rotavirus vaccine (RV1, Rotarix), which translates to an annual "excess of 96 hospitalizations ... and 5 deaths in the two countries combined." This risk is far exceeded by "the real-world benefits of RV1 vaccination, which has annually prevented more than 80,000 hospitalizations and 1,300 deaths in Mexico and Brazil," said Dr. Manish M. Patel of the Centers for Disease Control and Prevention, Atlanta, and his associates.

"These emerging data on safety and benefits have been reviewed by the World Health Organization as well as by regulatory agencies and immunization advisory committees in Brazil, Mexico, and the United States. ... [T]hese groups unanimously favored continuing the recommendation that rotavirus vaccination be administered to infants to prevent severe and potentially fatal rotavirus disease," the investigators noted (N. Engl. J. Med. 2011;364:2283-92).

They undertook this study because, after Brazil and Mexico added RV1 to their national childhood immunization programs in 2007, "the combined annual birth cohort of approximately 6 million in these two countries provided an opportunity to assess whether routine vaccination with RV1 was associated with intussusception," Dr. Patel and his colleagues wrote.

Using hospital records, they identified 615 infants who developed intussusception (285 in Mexico and 330 in Brazil) and matched them with 2,050 control infants (739 in Mexico and 1,311 in Brazil). Of these, 594 case patients (97%) and 2,033 controls (99%) had a history of vaccination confirmed by a vaccination card.

In Mexico, intussusception was significantly more likely to develop in the first week after the first dose of the vaccine than during other periods, with an incidence ratio of 5.3.

"This corresponds to the dose and period in which there is peak intestinal replication of vaccine virus and in which a local inflammatory response in the lymphatic tissue or intestines may occur – a response that has been implicated in the pathogenesis of intussusception," the investigators said.

In contrast, "neither a clustering of cases after the first dose nor a risk of the magnitude noted in Mexico was observed in Brazil. However, a small but significantly elevated rate was noted 1-7 days after the second dose," they said.

This absence of risk with the first RV1 dose was at first "perplexing." However, RV1 is administered together with oral poliovirus vaccine in Brazil but with inactivated poliovirus vaccine in Mexico. The first dose of oral polio vaccine is known to decrease the immunogenicity of RV1 when the two are given together, which may in turn reduce the risk of RV1-associated intussusception.

"Other factors, such as differences in the diets of the infants, breastfeeding practices, the natural risk of intussusception, and maternal antibody levels, might also have contributed to the variation in risk between Mexico and Brazil," Dr. Patel and his associates wrote.

"Our benefit-risk analysis indicated that an RV1 vaccination program would avert 663 deaths and 11,551 hospitalizations due to rotavirus disease in Mexico and 640 deaths and 69,572 hospitalizations in Brazil among children younger than 5 years of age.

"In contrast, we predict that a vaccination program would cause 41 excess hospitalizations (approximately 1 per 51,000 vaccinated infants) and 2 deaths due to intussusception in Mexico and 55 excess hospitalizations (approximately 1 per 68,000 vaccinated infants) and 3 deaths in Brazil," the researchers said.

They emphasized that the experience in Mexico may not apply to developing countries, most of which use the oral poliovirus vaccine. In addition, the immune response to rotavirus vaccination, as well as fecal shedding of vaccine strains of the virus, are generally lower in developing than in industrialized countries, which may indicate a difference in intussusception risk.

This study was funded in part by the GAVI Alliance under a collaborative agreement with the Program for Appropriate Technology in Health (PATH) and in part by the U.S. Department of Health and Human Services. Rotarix is a product of GlaxoSmithKline. Dr. Patel and his coinvestigators reported no relevant financial disclosures.

The second-generation rotavirus vaccine appears to raise the risk of intussusception in a similar manner as its predecessor, but its benefits still far outweigh that risk, according to a report in the June 16 issue of the New England Journal of Medicine. 

Case series and case-control analyses of immunization data from Mexico and Brazil indicate that the short-term risk of intussusception is approximately 1 in every 51,000-68,000 infants receiving the rotavirus vaccine (RV1, Rotarix), which translates to an annual "excess of 96 hospitalizations ... and 5 deaths in the two countries combined." This risk is far exceeded by "the real-world benefits of RV1 vaccination, which has annually prevented more than 80,000 hospitalizations and 1,300 deaths in Mexico and Brazil," said Dr. Manish M. Patel of the Centers for Disease Control and Prevention, Atlanta, and his associates.

"These emerging data on safety and benefits have been reviewed by the World Health Organization as well as by regulatory agencies and immunization advisory committees in Brazil, Mexico, and the United States. ... [T]hese groups unanimously favored continuing the recommendation that rotavirus vaccination be administered to infants to prevent severe and potentially fatal rotavirus disease," the investigators noted (N. Engl. J. Med. 2011;364:2283-92).

They undertook this study because, after Brazil and Mexico added RV1 to their national childhood immunization programs in 2007, "the combined annual birth cohort of approximately 6 million in these two countries provided an opportunity to assess whether routine vaccination with RV1 was associated with intussusception," Dr. Patel and his colleagues wrote.

Using hospital records, they identified 615 infants who developed intussusception (285 in Mexico and 330 in Brazil) and matched them with 2,050 control infants (739 in Mexico and 1,311 in Brazil). Of these, 594 case patients (97%) and 2,033 controls (99%) had a history of vaccination confirmed by a vaccination card.

In Mexico, intussusception was significantly more likely to develop in the first week after the first dose of the vaccine than during other periods, with an incidence ratio of 5.3.

"This corresponds to the dose and period in which there is peak intestinal replication of vaccine virus and in which a local inflammatory response in the lymphatic tissue or intestines may occur – a response that has been implicated in the pathogenesis of intussusception," the investigators said.

In contrast, "neither a clustering of cases after the first dose nor a risk of the magnitude noted in Mexico was observed in Brazil. However, a small but significantly elevated rate was noted 1-7 days after the second dose," they said.

This absence of risk with the first RV1 dose was at first "perplexing." However, RV1 is administered together with oral poliovirus vaccine in Brazil but with inactivated poliovirus vaccine in Mexico. The first dose of oral polio vaccine is known to decrease the immunogenicity of RV1 when the two are given together, which may in turn reduce the risk of RV1-associated intussusception.

"Other factors, such as differences in the diets of the infants, breastfeeding practices, the natural risk of intussusception, and maternal antibody levels, might also have contributed to the variation in risk between Mexico and Brazil," Dr. Patel and his associates wrote.

"Our benefit-risk analysis indicated that an RV1 vaccination program would avert 663 deaths and 11,551 hospitalizations due to rotavirus disease in Mexico and 640 deaths and 69,572 hospitalizations in Brazil among children younger than 5 years of age.

"In contrast, we predict that a vaccination program would cause 41 excess hospitalizations (approximately 1 per 51,000 vaccinated infants) and 2 deaths due to intussusception in Mexico and 55 excess hospitalizations (approximately 1 per 68,000 vaccinated infants) and 3 deaths in Brazil," the researchers said.

They emphasized that the experience in Mexico may not apply to developing countries, most of which use the oral poliovirus vaccine. In addition, the immune response to rotavirus vaccination, as well as fecal shedding of vaccine strains of the virus, are generally lower in developing than in industrialized countries, which may indicate a difference in intussusception risk.

This study was funded in part by the GAVI Alliance under a collaborative agreement with the Program for Appropriate Technology in Health (PATH) and in part by the U.S. Department of Health and Human Services. Rotarix is a product of GlaxoSmithKline. Dr. Patel and his coinvestigators reported no relevant financial disclosures.

More malpractice payments were made in 2009 for adverse events that happened in the outpatient setting than in the inpatient setting, according to a report in the June 15 issue of JAMA.

The outcomes of adverse events among outpatients "were not trivial," with death and major injury accounting for nearly two-thirds of those claims, said Dr. Tara F. Bishop of the department of public health at Weill Cornell Medical College, New York, and her associates.

The findings may come as a surprise, given that most initiatives addressing patient safety have centered on inpatient care. "For example, in the past 5 years, the number of studies funded by the Agency for Healthcare Research and Quality on inpatient safety has been almost 10-fold that of outpatient studies," the investigators noted (JAMA 2011;305:2427-31).

"Our findings provide empirical support for suggestions that patient safety initiatives should focus on the outpatient setting, not just on inpatient care," they said.

The researchers assessed trends in malpractice payments using data from the National Practitioner Data Bank, "a repository of all malpractice payments paid on behalf of practitioners in the United States." They performed a retrospective analysis of payments involving only MDs and DOs, including residents, and compared payments for adverse events that occurred in inpatient settings with those that occurred in outpatient settings between 2005 and 2009, the first and last dates for which complete data were available.

The researchers noted that their results are underestimates of actual malpractice payments, because the NPDB doesn’t track payments made on behalf of corporate entities.

Adverse events were classified into six categories: diagnostic, surgical, obstetric, treatment/medication, anesthesia, or other. The outcomes of those adverse events were classified as involving death, lifelong care, major injury, minor injury, or emotional injury.

In 2009, 10,739 payments were made on malpractice claims against physicians. In all, 4,910 of those (48%) were for adverse events that occurred in an inpatient setting, 4,448 (43%) were for events that occurred in an outpatient setting, and 966 (9%) were for events that occurred in both settings.

Thus, more than half (52%) of the adverse events "occurred in the outpatient setting, at least in part," the investigators noted.

The average payment amount for outpatient malpractice claims was approximately $300,000, and that amount did not change over time. "Almost $1.3 billion in malpractice claims was paid for outpatient events in 2009," the investigators noted.

Major injury was the most common patient outcome in both settings, accounting for 38% of inpatient and 36% of outpatient claim payments. Death was the next most common patient outcome, accounting for 36% of the inpatient and 31% of the outpatient claim payments.

For outpatients, the most common types of adverse events were diagnostic (46%), treatment (30%), and surgical (14%). In contrast, the most common type of adverse events for inpatients was surgical (34%), followed by diagnostic (21%) and treatment (20%). That indicates that "more attention should be paid to adverse events related to diagnostic errors" in outpatient practice, Dr. Bishop and her colleagues said.

"Events related to diagnosis may be particularly important in the outpatient setting, where follow-up is more difficult than in the hospital and where patients often present with symptoms and signs that may be subtle or not adequately noted amid the many short-term, long-term, and preventive care activities often undertaken in a single outpatient visit," they added.

Moreover, "the importance of adverse events related to diagnosis may be particularly relevant as pay-for-performance and public reporting programs increasingly demand attention from clinicians," Dr. Bishop and her associates said. "These programs do not reward diagnostic acuity or punish diagnostic error and may divert clinicians’ time and attention from the critical area of diagnosis."

The number of malpractice claims declined significantly over time in both inpatient and outpatient settings, but the rate of the decrease was lower for outpatient claims.

Dr. Bishop was supported in part as a Nanette Laitman Clinical Scholar in Public Health at Weill Cornell Medical College. An associate was supported in part by a grant from the Agency for Healthcare Research and Quality.

More malpractice payments were made in 2009 for adverse events that happened in the outpatient setting than in the inpatient setting, according to a report in the June 15 issue of JAMA.

The outcomes of adverse events among outpatients "were not trivial," with death and major injury accounting for nearly two-thirds of those claims, said Dr. Tara F. Bishop of the department of public health at Weill Cornell Medical College, New York, and her associates.

The findings may come as a surprise, given that most initiatives addressing patient safety have centered on inpatient care. "For example, in the past 5 years, the number of studies funded by the Agency for Healthcare Research and Quality on inpatient safety has been almost 10-fold that of outpatient studies," the investigators noted (JAMA 2011;305:2427-31).

"Our findings provide empirical support for suggestions that patient safety initiatives should focus on the outpatient setting, not just on inpatient care," they said.

The researchers assessed trends in malpractice payments using data from the National Practitioner Data Bank, "a repository of all malpractice payments paid on behalf of practitioners in the United States." They performed a retrospective analysis of payments involving only MDs and DOs, including residents, and compared payments for adverse events that occurred in inpatient settings with those that occurred in outpatient settings between 2005 and 2009, the first and last dates for which complete data were available.

The researchers noted that their results are underestimates of actual malpractice payments, because the NPDB doesn’t track payments made on behalf of corporate entities.

Adverse events were classified into six categories: diagnostic, surgical, obstetric, treatment/medication, anesthesia, or other. The outcomes of those adverse events were classified as involving death, lifelong care, major injury, minor injury, or emotional injury.

In 2009, 10,739 payments were made on malpractice claims against physicians. In all, 4,910 of those (48%) were for adverse events that occurred in an inpatient setting, 4,448 (43%) were for events that occurred in an outpatient setting, and 966 (9%) were for events that occurred in both settings.

Thus, more than half (52%) of the adverse events "occurred in the outpatient setting, at least in part," the investigators noted.

The average payment amount for outpatient malpractice claims was approximately $300,000, and that amount did not change over time. "Almost $1.3 billion in malpractice claims was paid for outpatient events in 2009," the investigators noted.

Major injury was the most common patient outcome in both settings, accounting for 38% of inpatient and 36% of outpatient claim payments. Death was the next most common patient outcome, accounting for 36% of the inpatient and 31% of the outpatient claim payments.

For outpatients, the most common types of adverse events were diagnostic (46%), treatment (30%), and surgical (14%). In contrast, the most common type of adverse events for inpatients was surgical (34%), followed by diagnostic (21%) and treatment (20%). That indicates that "more attention should be paid to adverse events related to diagnostic errors" in outpatient practice, Dr. Bishop and her colleagues said.

"Events related to diagnosis may be particularly important in the outpatient setting, where follow-up is more difficult than in the hospital and where patients often present with symptoms and signs that may be subtle or not adequately noted amid the many short-term, long-term, and preventive care activities often undertaken in a single outpatient visit," they added.

Moreover, "the importance of adverse events related to diagnosis may be particularly relevant as pay-for-performance and public reporting programs increasingly demand attention from clinicians," Dr. Bishop and her associates said. "These programs do not reward diagnostic acuity or punish diagnostic error and may divert clinicians’ time and attention from the critical area of diagnosis."

The number of malpractice claims declined significantly over time in both inpatient and outpatient settings, but the rate of the decrease was lower for outpatient claims.

Dr. Bishop was supported in part as a Nanette Laitman Clinical Scholar in Public Health at Weill Cornell Medical College. An associate was supported in part by a grant from the Agency for Healthcare Research and Quality.

More malpractice payments were made in 2009 for adverse events that happened in the outpatient setting than in the inpatient setting, according to a report in the June 15 issue of JAMA.

The outcomes of adverse events among outpatients "were not trivial," with death and major injury accounting for nearly two-thirds of those claims, said Dr. Tara F. Bishop of the department of public health at Weill Cornell Medical College, New York, and her associates.

The findings may come as a surprise, given that most initiatives addressing patient safety have centered on inpatient care. "For example, in the past 5 years, the number of studies funded by the Agency for Healthcare Research and Quality on inpatient safety has been almost 10-fold that of outpatient studies," the investigators noted (JAMA 2011;305:2427-31).

"Our findings provide empirical support for suggestions that patient safety initiatives should focus on the outpatient setting, not just on inpatient care," they said.

The researchers assessed trends in malpractice payments using data from the National Practitioner Data Bank, "a repository of all malpractice payments paid on behalf of practitioners in the United States." They performed a retrospective analysis of payments involving only MDs and DOs, including residents, and compared payments for adverse events that occurred in inpatient settings with those that occurred in outpatient settings between 2005 and 2009, the first and last dates for which complete data were available.

The researchers noted that their results are underestimates of actual malpractice payments, because the NPDB doesn’t track payments made on behalf of corporate entities.

Adverse events were classified into six categories: diagnostic, surgical, obstetric, treatment/medication, anesthesia, or other. The outcomes of those adverse events were classified as involving death, lifelong care, major injury, minor injury, or emotional injury.

In 2009, 10,739 payments were made on malpractice claims against physicians. In all, 4,910 of those (48%) were for adverse events that occurred in an inpatient setting, 4,448 (43%) were for events that occurred in an outpatient setting, and 966 (9%) were for events that occurred in both settings.

Thus, more than half (52%) of the adverse events "occurred in the outpatient setting, at least in part," the investigators noted.

The average payment amount for outpatient malpractice claims was approximately $300,000, and that amount did not change over time. "Almost $1.3 billion in malpractice claims was paid for outpatient events in 2009," the investigators noted.

Major injury was the most common patient outcome in both settings, accounting for 38% of inpatient and 36% of outpatient claim payments. Death was the next most common patient outcome, accounting for 36% of the inpatient and 31% of the outpatient claim payments.

For outpatients, the most common types of adverse events were diagnostic (46%), treatment (30%), and surgical (14%). In contrast, the most common type of adverse events for inpatients was surgical (34%), followed by diagnostic (21%) and treatment (20%). That indicates that "more attention should be paid to adverse events related to diagnostic errors" in outpatient practice, Dr. Bishop and her colleagues said.

"Events related to diagnosis may be particularly important in the outpatient setting, where follow-up is more difficult than in the hospital and where patients often present with symptoms and signs that may be subtle or not adequately noted amid the many short-term, long-term, and preventive care activities often undertaken in a single outpatient visit," they added.

Moreover, "the importance of adverse events related to diagnosis may be particularly relevant as pay-for-performance and public reporting programs increasingly demand attention from clinicians," Dr. Bishop and her associates said. "These programs do not reward diagnostic acuity or punish diagnostic error and may divert clinicians’ time and attention from the critical area of diagnosis."

The number of malpractice claims declined significantly over time in both inpatient and outpatient settings, but the rate of the decrease was lower for outpatient claims.

Dr. Bishop was supported in part as a Nanette Laitman Clinical Scholar in Public Health at Weill Cornell Medical College. An associate was supported in part by a grant from the Agency for Healthcare Research and Quality.