Diana Mahoney

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Statin therapy can reverse one of the most important side effects observed in clinical trials of the experimental oral biologic tofacitinib in rheumatoid arthritis, a study has shown.

Concomitant treatment with atorvastatin significantly lessened dyslipidemia observed in a cohort of rheumatoid arthritis patients taking tofacitinib in a phase II trial.

Of 111 rheumatoid arthritis patients enrolled in the study, tofacitinib-treated patients who took atorvastatin (Lipitor) following an open-label lead-in period had a 35% reduction in mean low-density lipoprotein cholesterol (LDL-C) compared with a 5.8% increase observed in tofacitinib-treated patients randomized to concomitant placebo. Those who took atorvastatin had improvements in other lipid measures as well, reported Dr. Iain McInnes of the University of Glasgow (Scotland).

Treatment with tofacitinib, an oral Janus kinase (JAK) inhibitor being investigated as a targeted immunomodulator, has been associated with increases in serum lipids, including LDL and HDL cholesterol and triglycerides in phase II and III rheumatoid arthritis trials, said Dr. McInnes. The same effect is seen with other JAK inhibitors. Certain proinflammatory cytokines have been shown to have an effect on serum lipid levels. Considering the synergy between inflammation and lipid metabolism, "it should be no surprise at all that an agent that modifies inflammation can also cause metabolic changes," he said at the annual European Congress of Rheumatology.

To evaluate whether use of a lipid-lowering drug could safely and effectively modulate lipid increases associated with tofacitinib treatment, Dr. McInnes and his colleagues evaluated the lipid levels of study patients who completed 6 weeks of 10-mg tofacitinib twice daily and were subsequently randomized to an additional 6 weeks of treatment with concomitant atorvastatin or placebo.

From baseline to week 6 of tofacitinib therapy, the average increases for the predominantly female study group (mean age, 52 years) were 185-230 mg/dL for total cholesterol; 109-126 mg/dL for LDL-C; 51-67 mg/dL for high-density lipoprotein cholesterol (HDL-C); 136-165 mg/dL for apolipoprotein A-1; 87-97 mg/dL for apolipoprotein B; and 100-109 mg/dL for triglycerides, Dr. McInnes reported. By week 12, total cholesterol, LDL-C, apolipoprotein B, and triglycerides were significantly decreased in the atorvastatin patients relative to placebo, "to levels below those observed at baseline," he said, while the HDL-C levels increased similarly in both the placebo and atorvastatin groups from week 6 to week 12.

With respect to clinical responses, at week 6, a minimum 20% improvement in American College of Rheumatology criteria (ACR20) was seen in 76% of the study population. "By week 12, 82.6% of the atorvastatin group exhibited an ACR20 response, compared with 65.2% of the placebo group, and 67.4% of the atorvastatin group vs. 45.7% exhibited a minimum 50% improvement in ACR criteria [ACR50)," said Dr. McInnes, who noted that, although the differences in clinical response between the atorvastatin and placebo groups were not statistically significant, the trend toward additional improvements are notable and warrant further study.

In safety analyses, the investigators observed a safety profile similar to that reported in other tofacitinib trials in rheumatoid arthritis, said Dr. McInnes. Specifically, treatment-related adverse events were experienced by 23.4% of the patients during the first 6 weeks of the study, and by 10% of the atorvastatin group and 17% of the placebo group from week 6 to week 12, said Dr. McInnes. Serious adverse events, including pneumonia, occurred in 1.8% of the patients during the open-label phase of the study, he said, noting that none of the atorvastatin patients and 2.1% of the placebo patients experienced serious adverse events between weeks 6 and 12.

"The findings of this study are important in that they demonstrate that any changes in lipids are reversible by addition of a statin," Dr. McInnes said in an interview. "It’s too early to determine how statins and tofacitinib will be used in standard of care. More data are required at this stage."

Dr. Joel Kremer agreed. The chief of medicine at Albany Medical College in New York, Dr. Kremer was the lead investigator of a phase III trial that he reported at the meeting. Data from the phase III trial demonstrated the efficacy of tofacitinib in rheumatoid arthritis patients who failed to respond to treatment with other disease-modifying antirheumatic drugs.

In an interview, Dr. Kremer noted that it’s uncertain whether concurrent lipid-lowering therapy will be considered routine standard of care with tofacitinib in rheumatoid arthritis patients, "but it probably will become quite common, as it is becoming common with Actemra [tocilizumab]."

Dr. McInnes and Dr. Kremer disclosed receiving grant and research support from and serving as consultants for Pfizer.

LONDON – Statin therapy can reverse one of the most important side effects observed in clinical trials of the experimental oral biologic tofacitinib in rheumatoid arthritis, a study has shown.

Concomitant treatment with atorvastatin significantly lessened dyslipidemia observed in a cohort of rheumatoid arthritis patients taking tofacitinib in a phase II trial.

Of 111 rheumatoid arthritis patients enrolled in the study, tofacitinib-treated patients who took atorvastatin (Lipitor) following an open-label lead-in period had a 35% reduction in mean low-density lipoprotein cholesterol (LDL-C) compared with a 5.8% increase observed in tofacitinib-treated patients randomized to concomitant placebo. Those who took atorvastatin had improvements in other lipid measures as well, reported Dr. Iain McInnes of the University of Glasgow (Scotland).

Treatment with tofacitinib, an oral Janus kinase (JAK) inhibitor being investigated as a targeted immunomodulator, has been associated with increases in serum lipids, including LDL and HDL cholesterol and triglycerides in phase II and III rheumatoid arthritis trials, said Dr. McInnes. The same effect is seen with other JAK inhibitors. Certain proinflammatory cytokines have been shown to have an effect on serum lipid levels. Considering the synergy between inflammation and lipid metabolism, "it should be no surprise at all that an agent that modifies inflammation can also cause metabolic changes," he said at the annual European Congress of Rheumatology.

To evaluate whether use of a lipid-lowering drug could safely and effectively modulate lipid increases associated with tofacitinib treatment, Dr. McInnes and his colleagues evaluated the lipid levels of study patients who completed 6 weeks of 10-mg tofacitinib twice daily and were subsequently randomized to an additional 6 weeks of treatment with concomitant atorvastatin or placebo.

From baseline to week 6 of tofacitinib therapy, the average increases for the predominantly female study group (mean age, 52 years) were 185-230 mg/dL for total cholesterol; 109-126 mg/dL for LDL-C; 51-67 mg/dL for high-density lipoprotein cholesterol (HDL-C); 136-165 mg/dL for apolipoprotein A-1; 87-97 mg/dL for apolipoprotein B; and 100-109 mg/dL for triglycerides, Dr. McInnes reported. By week 12, total cholesterol, LDL-C, apolipoprotein B, and triglycerides were significantly decreased in the atorvastatin patients relative to placebo, "to levels below those observed at baseline," he said, while the HDL-C levels increased similarly in both the placebo and atorvastatin groups from week 6 to week 12.

With respect to clinical responses, at week 6, a minimum 20% improvement in American College of Rheumatology criteria (ACR20) was seen in 76% of the study population. "By week 12, 82.6% of the atorvastatin group exhibited an ACR20 response, compared with 65.2% of the placebo group, and 67.4% of the atorvastatin group vs. 45.7% exhibited a minimum 50% improvement in ACR criteria [ACR50)," said Dr. McInnes, who noted that, although the differences in clinical response between the atorvastatin and placebo groups were not statistically significant, the trend toward additional improvements are notable and warrant further study.

In safety analyses, the investigators observed a safety profile similar to that reported in other tofacitinib trials in rheumatoid arthritis, said Dr. McInnes. Specifically, treatment-related adverse events were experienced by 23.4% of the patients during the first 6 weeks of the study, and by 10% of the atorvastatin group and 17% of the placebo group from week 6 to week 12, said Dr. McInnes. Serious adverse events, including pneumonia, occurred in 1.8% of the patients during the open-label phase of the study, he said, noting that none of the atorvastatin patients and 2.1% of the placebo patients experienced serious adverse events between weeks 6 and 12.

"The findings of this study are important in that they demonstrate that any changes in lipids are reversible by addition of a statin," Dr. McInnes said in an interview. "It’s too early to determine how statins and tofacitinib will be used in standard of care. More data are required at this stage."

Dr. Joel Kremer agreed. The chief of medicine at Albany Medical College in New York, Dr. Kremer was the lead investigator of a phase III trial that he reported at the meeting. Data from the phase III trial demonstrated the efficacy of tofacitinib in rheumatoid arthritis patients who failed to respond to treatment with other disease-modifying antirheumatic drugs.

In an interview, Dr. Kremer noted that it’s uncertain whether concurrent lipid-lowering therapy will be considered routine standard of care with tofacitinib in rheumatoid arthritis patients, "but it probably will become quite common, as it is becoming common with Actemra [tocilizumab]."

Dr. McInnes and Dr. Kremer disclosed receiving grant and research support from and serving as consultants for Pfizer.

LONDON – Statin therapy can reverse one of the most important side effects observed in clinical trials of the experimental oral biologic tofacitinib in rheumatoid arthritis, a study has shown.

Concomitant treatment with atorvastatin significantly lessened dyslipidemia observed in a cohort of rheumatoid arthritis patients taking tofacitinib in a phase II trial.

Of 111 rheumatoid arthritis patients enrolled in the study, tofacitinib-treated patients who took atorvastatin (Lipitor) following an open-label lead-in period had a 35% reduction in mean low-density lipoprotein cholesterol (LDL-C) compared with a 5.8% increase observed in tofacitinib-treated patients randomized to concomitant placebo. Those who took atorvastatin had improvements in other lipid measures as well, reported Dr. Iain McInnes of the University of Glasgow (Scotland).

Treatment with tofacitinib, an oral Janus kinase (JAK) inhibitor being investigated as a targeted immunomodulator, has been associated with increases in serum lipids, including LDL and HDL cholesterol and triglycerides in phase II and III rheumatoid arthritis trials, said Dr. McInnes. The same effect is seen with other JAK inhibitors. Certain proinflammatory cytokines have been shown to have an effect on serum lipid levels. Considering the synergy between inflammation and lipid metabolism, "it should be no surprise at all that an agent that modifies inflammation can also cause metabolic changes," he said at the annual European Congress of Rheumatology.

To evaluate whether use of a lipid-lowering drug could safely and effectively modulate lipid increases associated with tofacitinib treatment, Dr. McInnes and his colleagues evaluated the lipid levels of study patients who completed 6 weeks of 10-mg tofacitinib twice daily and were subsequently randomized to an additional 6 weeks of treatment with concomitant atorvastatin or placebo.

From baseline to week 6 of tofacitinib therapy, the average increases for the predominantly female study group (mean age, 52 years) were 185-230 mg/dL for total cholesterol; 109-126 mg/dL for LDL-C; 51-67 mg/dL for high-density lipoprotein cholesterol (HDL-C); 136-165 mg/dL for apolipoprotein A-1; 87-97 mg/dL for apolipoprotein B; and 100-109 mg/dL for triglycerides, Dr. McInnes reported. By week 12, total cholesterol, LDL-C, apolipoprotein B, and triglycerides were significantly decreased in the atorvastatin patients relative to placebo, "to levels below those observed at baseline," he said, while the HDL-C levels increased similarly in both the placebo and atorvastatin groups from week 6 to week 12.

With respect to clinical responses, at week 6, a minimum 20% improvement in American College of Rheumatology criteria (ACR20) was seen in 76% of the study population. "By week 12, 82.6% of the atorvastatin group exhibited an ACR20 response, compared with 65.2% of the placebo group, and 67.4% of the atorvastatin group vs. 45.7% exhibited a minimum 50% improvement in ACR criteria [ACR50)," said Dr. McInnes, who noted that, although the differences in clinical response between the atorvastatin and placebo groups were not statistically significant, the trend toward additional improvements are notable and warrant further study.

In safety analyses, the investigators observed a safety profile similar to that reported in other tofacitinib trials in rheumatoid arthritis, said Dr. McInnes. Specifically, treatment-related adverse events were experienced by 23.4% of the patients during the first 6 weeks of the study, and by 10% of the atorvastatin group and 17% of the placebo group from week 6 to week 12, said Dr. McInnes. Serious adverse events, including pneumonia, occurred in 1.8% of the patients during the open-label phase of the study, he said, noting that none of the atorvastatin patients and 2.1% of the placebo patients experienced serious adverse events between weeks 6 and 12.

"The findings of this study are important in that they demonstrate that any changes in lipids are reversible by addition of a statin," Dr. McInnes said in an interview. "It’s too early to determine how statins and tofacitinib will be used in standard of care. More data are required at this stage."

Dr. Joel Kremer agreed. The chief of medicine at Albany Medical College in New York, Dr. Kremer was the lead investigator of a phase III trial that he reported at the meeting. Data from the phase III trial demonstrated the efficacy of tofacitinib in rheumatoid arthritis patients who failed to respond to treatment with other disease-modifying antirheumatic drugs.

In an interview, Dr. Kremer noted that it’s uncertain whether concurrent lipid-lowering therapy will be considered routine standard of care with tofacitinib in rheumatoid arthritis patients, "but it probably will become quite common, as it is becoming common with Actemra [tocilizumab]."

Dr. McInnes and Dr. Kremer disclosed receiving grant and research support from and serving as consultants for Pfizer.

LONDON – Statin therapy can reverse one of the most important side effects observed in clinical trials of the experimental oral biologic tofacitinib in rheumatoid arthritis, a study has shown.

Concomitant treatment with atorvastatin significantly lessened dyslipidemia observed in a cohort of rheumatoid arthritis patients taking tofacitinib in a phase II trial.

Of 111 rheumatoid arthritis patients enrolled in the study, tofacitinib-treated patients who took atorvastatin (Lipitor) following an open-label lead-in period had a 35% reduction in mean low-density lipoprotein cholesterol (LDL-C) compared with a 5.8% increase observed in tofacitinib-treated patients randomized to concomitant placebo. Those who took atorvastatin had improvements in other lipid measures as well, reported Dr. Iain McInnes of the University of Glasgow (Scotland).

Treatment with tofacitinib, an oral Janus kinase (JAK) inhibitor being investigated as a targeted immunomodulator, has been associated with increases in serum lipids, including LDL and HDL cholesterol and triglycerides in phase II and III rheumatoid arthritis trials, said Dr. McInnes. The same effect is seen with other JAK inhibitors. Certain proinflammatory cytokines have been shown to have an effect on serum lipid levels. Considering the synergy between inflammation and lipid metabolism, "it should be no surprise at all that an agent that modifies inflammation can also cause metabolic changes," he said at the annual European Congress of Rheumatology.

To evaluate whether use of a lipid-lowering drug could safely and effectively modulate lipid increases associated with tofacitinib treatment, Dr. McInnes and his colleagues evaluated the lipid levels of study patients who completed 6 weeks of 10-mg tofacitinib twice daily and were subsequently randomized to an additional 6 weeks of treatment with concomitant atorvastatin or placebo.

From baseline to week 6 of tofacitinib therapy, the average increases for the predominantly female study group (mean age, 52 years) were 185-230 mg/dL for total cholesterol; 109-126 mg/dL for LDL-C; 51-67 mg/dL for high-density lipoprotein cholesterol (HDL-C); 136-165 mg/dL for apolipoprotein A-1; 87-97 mg/dL for apolipoprotein B; and 100-109 mg/dL for triglycerides, Dr. McInnes reported. By week 12, total cholesterol, LDL-C, apolipoprotein B, and triglycerides were significantly decreased in the atorvastatin patients relative to placebo, "to levels below those observed at baseline," he said, while the HDL-C levels increased similarly in both the placebo and atorvastatin groups from week 6 to week 12.

With respect to clinical responses, at week 6, a minimum 20% improvement in American College of Rheumatology criteria (ACR20) was seen in 76% of the study population. "By week 12, 82.6% of the atorvastatin group exhibited an ACR20 response, compared with 65.2% of the placebo group, and 67.4% of the atorvastatin group vs. 45.7% exhibited a minimum 50% improvement in ACR criteria [ACR50)," said Dr. McInnes, who noted that, although the differences in clinical response between the atorvastatin and placebo groups were not statistically significant, the trend toward additional improvements are notable and warrant further study.

In safety analyses, the investigators observed a safety profile similar to that reported in other tofacitinib trials in rheumatoid arthritis, said Dr. McInnes. Specifically, treatment-related adverse events were experienced by 23.4% of the patients during the first 6 weeks of the study, and by 10% of the atorvastatin group and 17% of the placebo group from week 6 to week 12, said Dr. McInnes. Serious adverse events, including pneumonia, occurred in 1.8% of the patients during the open-label phase of the study, he said, noting that none of the atorvastatin patients and 2.1% of the placebo patients experienced serious adverse events between weeks 6 and 12.

"The findings of this study are important in that they demonstrate that any changes in lipids are reversible by addition of a statin," Dr. McInnes said in an interview. "It’s too early to determine how statins and tofacitinib will be used in standard of care. More data are required at this stage."

Dr. Joel Kremer agreed. The chief of medicine at Albany Medical College in New York, Dr. Kremer was the lead investigator of a phase III trial that he reported at the meeting. Data from the phase III trial demonstrated the efficacy of tofacitinib in rheumatoid arthritis patients who failed to respond to treatment with other disease-modifying antirheumatic drugs.

In an interview, Dr. Kremer noted that it’s uncertain whether concurrent lipid-lowering therapy will be considered routine standard of care with tofacitinib in rheumatoid arthritis patients, "but it probably will become quite common, as it is becoming common with Actemra [tocilizumab]."

Dr. McInnes and Dr. Kremer disclosed receiving grant and research support from and serving as consultants for Pfizer.

LONDON – Statin therapy can reverse one of the most important side effects observed in clinical trials of the experimental oral biologic tofacitinib in rheumatoid arthritis, a study has shown.

Concomitant treatment with atorvastatin significantly lessened dyslipidemia observed in a cohort of rheumatoid arthritis patients taking tofacitinib in a phase II trial.

Of 111 rheumatoid arthritis patients enrolled in the study, tofacitinib-treated patients who took atorvastatin (Lipitor) following an open-label lead-in period had a 35% reduction in mean low-density lipoprotein cholesterol (LDL-C) compared with a 5.8% increase observed in tofacitinib-treated patients randomized to concomitant placebo. Those who took atorvastatin had improvements in other lipid measures as well, reported Dr. Iain McInnes of the University of Glasgow (Scotland).

Treatment with tofacitinib, an oral Janus kinase (JAK) inhibitor being investigated as a targeted immunomodulator, has been associated with increases in serum lipids, including LDL and HDL cholesterol and triglycerides in phase II and III rheumatoid arthritis trials, said Dr. McInnes. The same effect is seen with other JAK inhibitors. Certain proinflammatory cytokines have been shown to have an effect on serum lipid levels. Considering the synergy between inflammation and lipid metabolism, "it should be no surprise at all that an agent that modifies inflammation can also cause metabolic changes," he said at the annual European Congress of Rheumatology.

To evaluate whether use of a lipid-lowering drug could safely and effectively modulate lipid increases associated with tofacitinib treatment, Dr. McInnes and his colleagues evaluated the lipid levels of study patients who completed 6 weeks of 10-mg tofacitinib twice daily and were subsequently randomized to an additional 6 weeks of treatment with concomitant atorvastatin or placebo.

From baseline to week 6 of tofacitinib therapy, the average increases for the predominantly female study group (mean age, 52 years) were 185-230 mg/dL for total cholesterol; 109-126 mg/dL for LDL-C; 51-67 mg/dL for high-density lipoprotein cholesterol (HDL-C); 136-165 mg/dL for apolipoprotein A-1; 87-97 mg/dL for apolipoprotein B; and 100-109 mg/dL for triglycerides, Dr. McInnes reported. By week 12, total cholesterol, LDL-C, apolipoprotein B, and triglycerides were significantly decreased in the atorvastatin patients relative to placebo, "to levels below those observed at baseline," he said, while the HDL-C levels increased similarly in both the placebo and atorvastatin groups from week 6 to week 12.

With respect to clinical responses, at week 6, a minimum 20% improvement in American College of Rheumatology criteria (ACR20) was seen in 76% of the study population. "By week 12, 82.6% of the atorvastatin group exhibited an ACR20 response, compared with 65.2% of the placebo group, and 67.4% of the atorvastatin group vs. 45.7% exhibited a minimum 50% improvement in ACR criteria [ACR50)," said Dr. McInnes, who noted that, although the differences in clinical response between the atorvastatin and placebo groups were not statistically significant, the trend toward additional improvements are notable and warrant further study.

In safety analyses, the investigators observed a safety profile similar to that reported in other tofacitinib trials in rheumatoid arthritis, said Dr. McInnes. Specifically, treatment-related adverse events were experienced by 23.4% of the patients during the first 6 weeks of the study, and by 10% of the atorvastatin group and 17% of the placebo group from week 6 to week 12, said Dr. McInnes. Serious adverse events, including pneumonia, occurred in 1.8% of the patients during the open-label phase of the study, he said, noting that none of the atorvastatin patients and 2.1% of the placebo patients experienced serious adverse events between weeks 6 and 12.

"The findings of this study are important in that they demonstrate that any changes in lipids are reversible by addition of a statin," Dr. McInnes said in an interview. "It’s too early to determine how statins and tofacitinib will be used in standard of care. More data are required at this stage."

Dr. Joel Kremer agreed. The chief of medicine at Albany Medical College in New York, Dr. Kremer was the lead investigator of a phase III trial that he reported at the meeting. Data from the phase III trial demonstrated the efficacy of tofacitinib in rheumatoid arthritis patients who failed to respond to treatment with other disease-modifying antirheumatic drugs.

In an interview, Dr. Kremer noted that it’s uncertain whether concurrent lipid-lowering therapy will be considered routine standard of care with tofacitinib in rheumatoid arthritis patients, "but it probably will become quite common, as it is becoming common with Actemra [tocilizumab]."

Dr. McInnes and Dr. Kremer disclosed receiving grant and research support from and serving as consultants for Pfizer.

LONDON – Statin therapy can reverse one of the most important side effects observed in clinical trials of the experimental oral biologic tofacitinib in rheumatoid arthritis, a study has shown.

Concomitant treatment with atorvastatin significantly lessened dyslipidemia observed in a cohort of rheumatoid arthritis patients taking tofacitinib in a phase II trial.

Of 111 rheumatoid arthritis patients enrolled in the study, tofacitinib-treated patients who took atorvastatin (Lipitor) following an open-label lead-in period had a 35% reduction in mean low-density lipoprotein cholesterol (LDL-C) compared with a 5.8% increase observed in tofacitinib-treated patients randomized to concomitant placebo. Those who took atorvastatin had improvements in other lipid measures as well, reported Dr. Iain McInnes of the University of Glasgow (Scotland).

Treatment with tofacitinib, an oral Janus kinase (JAK) inhibitor being investigated as a targeted immunomodulator, has been associated with increases in serum lipids, including LDL and HDL cholesterol and triglycerides in phase II and III rheumatoid arthritis trials, said Dr. McInnes. The same effect is seen with other JAK inhibitors. Certain proinflammatory cytokines have been shown to have an effect on serum lipid levels. Considering the synergy between inflammation and lipid metabolism, "it should be no surprise at all that an agent that modifies inflammation can also cause metabolic changes," he said at the annual European Congress of Rheumatology.

To evaluate whether use of a lipid-lowering drug could safely and effectively modulate lipid increases associated with tofacitinib treatment, Dr. McInnes and his colleagues evaluated the lipid levels of study patients who completed 6 weeks of 10-mg tofacitinib twice daily and were subsequently randomized to an additional 6 weeks of treatment with concomitant atorvastatin or placebo.

From baseline to week 6 of tofacitinib therapy, the average increases for the predominantly female study group (mean age, 52 years) were 185-230 mg/dL for total cholesterol; 109-126 mg/dL for LDL-C; 51-67 mg/dL for high-density lipoprotein cholesterol (HDL-C); 136-165 mg/dL for apolipoprotein A-1; 87-97 mg/dL for apolipoprotein B; and 100-109 mg/dL for triglycerides, Dr. McInnes reported. By week 12, total cholesterol, LDL-C, apolipoprotein B, and triglycerides were significantly decreased in the atorvastatin patients relative to placebo, "to levels below those observed at baseline," he said, while the HDL-C levels increased similarly in both the placebo and atorvastatin groups from week 6 to week 12.

With respect to clinical responses, at week 6, a minimum 20% improvement in American College of Rheumatology criteria (ACR20) was seen in 76% of the study population. "By week 12, 82.6% of the atorvastatin group exhibited an ACR20 response, compared with 65.2% of the placebo group, and 67.4% of the atorvastatin group vs. 45.7% exhibited a minimum 50% improvement in ACR criteria [ACR50)," said Dr. McInnes, who noted that, although the differences in clinical response between the atorvastatin and placebo groups were not statistically significant, the trend toward additional improvements are notable and warrant further study.

In safety analyses, the investigators observed a safety profile similar to that reported in other tofacitinib trials in rheumatoid arthritis, said Dr. McInnes. Specifically, treatment-related adverse events were experienced by 23.4% of the patients during the first 6 weeks of the study, and by 10% of the atorvastatin group and 17% of the placebo group from week 6 to week 12, said Dr. McInnes. Serious adverse events, including pneumonia, occurred in 1.8% of the patients during the open-label phase of the study, he said, noting that none of the atorvastatin patients and 2.1% of the placebo patients experienced serious adverse events between weeks 6 and 12.

"The findings of this study are important in that they demonstrate that any changes in lipids are reversible by addition of a statin," Dr. McInnes said in an interview. "It’s too early to determine how statins and tofacitinib will be used in standard of care. More data are required at this stage."

Dr. Joel Kremer agreed. The chief of medicine at Albany Medical College in New York, Dr. Kremer was the lead investigator of a phase III trial that he reported at the meeting. Data from the phase III trial demonstrated the efficacy of tofacitinib in rheumatoid arthritis patients who failed to respond to treatment with other disease-modifying antirheumatic drugs.

In an interview, Dr. Kremer noted that it’s uncertain whether concurrent lipid-lowering therapy will be considered routine standard of care with tofacitinib in rheumatoid arthritis patients, "but it probably will become quite common, as it is becoming common with Actemra [tocilizumab]."

Dr. McInnes and Dr. Kremer disclosed receiving grant and research support from and serving as consultants for Pfizer.

LONDON – Gout is an independent risk factor for acute myocardial infarction, even among younger patients and those without cardiovascular risk factors, according to Dr. Chang-Fu Kuo, who presented a late-breaking report at the Annual European Congress of Rheumatology.

The risk for acute MI was 23% higher among gout patients than the general population, judging from an analysis of a large Taiwanese database. Among individuals aged 20-44 years old and those without additional cardiovascular risk factors, the risk of acute MI was increased by 59% and 76%, respectively, reported Dr. Kuo of Chang Gung Memorial Hospital, Taipei, Taiwan.

To investigate the risk of acute MI associated with gout, Dr. Kuo and colleagues analyzed the 2000 Taiwan National Health Insurance database, which is a representative sampling cohort of the general population. Specifically, the investigators compared rates of first hospital admission for acute MI among gout and nongout patients aged 20 years or older. Of the 704,503 individuals included in the cohort (mean age, 42.73 years), 26,566 were diagnosed and treated for gout in 1996-1999, Dr. Kuo said. Compared with the nongout patients, "the gout patients were significantly older, with a mean age of 55.4 years, and they were significantly more likely to have diabetes and hypertension," he said.

The investigators followed the cohort from January 2000 through December 2008, for a total of 5.6 million patient-years of follow-up. During this period, 3,718 patients were hospitalized for acute MI, including 463 patients with gout. Of these events, 299 were fatal, including 35 in gout patients, Dr. Kuo said. "The incidence of acute [MI] in gout patients was 2.20 per 1,000 patient years and was significantly higher than in nongout patients, which was 0.60," he said.

In the multivariate model adjusted for age, sex, diabetes, hypertension, coronary heart disease, stroke, and end-stage renal disease, the respective hazard ratios for all acute MI and nonfatal acute MI in gout patients were 1.23 and 1.26, Dr. Kuo reported. "In patients without cardiovascular risk factors, the hazard ratio for all acute [MI] was 1.84, and for nonfatal acute [MI] was 1.80," he said, and when assessed by age, the respective hazard ratios for gout patients aged 20-44 years, 45-59 years, and 60 years or older were 1.59, 1.24, and 1.11.

The multivariate model was not adjusted for hyperlipidemia, which has been associated with gout, Dr. Kuo said, acknowledging that elevated lipid levels could play an important role in the increased cardiovascular risks observed in the gout patients.

Although the increased risk of acute MI associated with gout has been previously reported, "the risk in younger patients and those with low risk profiles hasn’t previously been established," Dr. Kuo explained. The finding that gout is an independent risk factor for the occurrence of acute MI – particularly nonfatal acute MI – among young, low-risk patients suggests the need for "vigilant cardiovascular monitoring" of these patients, he stressed.

Dr. Kuo reported having no conflicts of interest to disclose.

LONDON – Gout is an independent risk factor for acute myocardial infarction, even among younger patients and those without cardiovascular risk factors, according to Dr. Chang-Fu Kuo, who presented a late-breaking report at the Annual European Congress of Rheumatology.

The risk for acute MI was 23% higher among gout patients than the general population, judging from an analysis of a large Taiwanese database. Among individuals aged 20-44 years old and those without additional cardiovascular risk factors, the risk of acute MI was increased by 59% and 76%, respectively, reported Dr. Kuo of Chang Gung Memorial Hospital, Taipei, Taiwan.

To investigate the risk of acute MI associated with gout, Dr. Kuo and colleagues analyzed the 2000 Taiwan National Health Insurance database, which is a representative sampling cohort of the general population. Specifically, the investigators compared rates of first hospital admission for acute MI among gout and nongout patients aged 20 years or older. Of the 704,503 individuals included in the cohort (mean age, 42.73 years), 26,566 were diagnosed and treated for gout in 1996-1999, Dr. Kuo said. Compared with the nongout patients, "the gout patients were significantly older, with a mean age of 55.4 years, and they were significantly more likely to have diabetes and hypertension," he said.

The investigators followed the cohort from January 2000 through December 2008, for a total of 5.6 million patient-years of follow-up. During this period, 3,718 patients were hospitalized for acute MI, including 463 patients with gout. Of these events, 299 were fatal, including 35 in gout patients, Dr. Kuo said. "The incidence of acute [MI] in gout patients was 2.20 per 1,000 patient years and was significantly higher than in nongout patients, which was 0.60," he said.

In the multivariate model adjusted for age, sex, diabetes, hypertension, coronary heart disease, stroke, and end-stage renal disease, the respective hazard ratios for all acute MI and nonfatal acute MI in gout patients were 1.23 and 1.26, Dr. Kuo reported. "In patients without cardiovascular risk factors, the hazard ratio for all acute [MI] was 1.84, and for nonfatal acute [MI] was 1.80," he said, and when assessed by age, the respective hazard ratios for gout patients aged 20-44 years, 45-59 years, and 60 years or older were 1.59, 1.24, and 1.11.

The multivariate model was not adjusted for hyperlipidemia, which has been associated with gout, Dr. Kuo said, acknowledging that elevated lipid levels could play an important role in the increased cardiovascular risks observed in the gout patients.

Although the increased risk of acute MI associated with gout has been previously reported, "the risk in younger patients and those with low risk profiles hasn’t previously been established," Dr. Kuo explained. The finding that gout is an independent risk factor for the occurrence of acute MI – particularly nonfatal acute MI – among young, low-risk patients suggests the need for "vigilant cardiovascular monitoring" of these patients, he stressed.

Dr. Kuo reported having no conflicts of interest to disclose.

LONDON – Gout is an independent risk factor for acute myocardial infarction, even among younger patients and those without cardiovascular risk factors, according to Dr. Chang-Fu Kuo, who presented a late-breaking report at the Annual European Congress of Rheumatology.

The risk for acute MI was 23% higher among gout patients than the general population, judging from an analysis of a large Taiwanese database. Among individuals aged 20-44 years old and those without additional cardiovascular risk factors, the risk of acute MI was increased by 59% and 76%, respectively, reported Dr. Kuo of Chang Gung Memorial Hospital, Taipei, Taiwan.

To investigate the risk of acute MI associated with gout, Dr. Kuo and colleagues analyzed the 2000 Taiwan National Health Insurance database, which is a representative sampling cohort of the general population. Specifically, the investigators compared rates of first hospital admission for acute MI among gout and nongout patients aged 20 years or older. Of the 704,503 individuals included in the cohort (mean age, 42.73 years), 26,566 were diagnosed and treated for gout in 1996-1999, Dr. Kuo said. Compared with the nongout patients, "the gout patients were significantly older, with a mean age of 55.4 years, and they were significantly more likely to have diabetes and hypertension," he said.

The investigators followed the cohort from January 2000 through December 2008, for a total of 5.6 million patient-years of follow-up. During this period, 3,718 patients were hospitalized for acute MI, including 463 patients with gout. Of these events, 299 were fatal, including 35 in gout patients, Dr. Kuo said. "The incidence of acute [MI] in gout patients was 2.20 per 1,000 patient years and was significantly higher than in nongout patients, which was 0.60," he said.

In the multivariate model adjusted for age, sex, diabetes, hypertension, coronary heart disease, stroke, and end-stage renal disease, the respective hazard ratios for all acute MI and nonfatal acute MI in gout patients were 1.23 and 1.26, Dr. Kuo reported. "In patients without cardiovascular risk factors, the hazard ratio for all acute [MI] was 1.84, and for nonfatal acute [MI] was 1.80," he said, and when assessed by age, the respective hazard ratios for gout patients aged 20-44 years, 45-59 years, and 60 years or older were 1.59, 1.24, and 1.11.

The multivariate model was not adjusted for hyperlipidemia, which has been associated with gout, Dr. Kuo said, acknowledging that elevated lipid levels could play an important role in the increased cardiovascular risks observed in the gout patients.

Although the increased risk of acute MI associated with gout has been previously reported, "the risk in younger patients and those with low risk profiles hasn’t previously been established," Dr. Kuo explained. The finding that gout is an independent risk factor for the occurrence of acute MI – particularly nonfatal acute MI – among young, low-risk patients suggests the need for "vigilant cardiovascular monitoring" of these patients, he stressed.

Dr. Kuo reported having no conflicts of interest to disclose.

LONDON – Gout is an independent risk factor for acute myocardial infarction, even among younger patients and those without cardiovascular risk factors, according to Dr. Chang-Fu Kuo, who presented a late-breaking report at the Annual European Congress of Rheumatology.

The risk for acute MI was 23% higher among gout patients than the general population, judging from an analysis of a large Taiwanese database. Among individuals aged 20-44 years old and those without additional cardiovascular risk factors, the risk of acute MI was increased by 59% and 76%, respectively, reported Dr. Kuo of Chang Gung Memorial Hospital, Taipei, Taiwan.

To investigate the risk of acute MI associated with gout, Dr. Kuo and colleagues analyzed the 2000 Taiwan National Health Insurance database, which is a representative sampling cohort of the general population. Specifically, the investigators compared rates of first hospital admission for acute MI among gout and nongout patients aged 20 years or older. Of the 704,503 individuals included in the cohort (mean age, 42.73 years), 26,566 were diagnosed and treated for gout in 1996-1999, Dr. Kuo said. Compared with the nongout patients, "the gout patients were significantly older, with a mean age of 55.4 years, and they were significantly more likely to have diabetes and hypertension," he said.

The investigators followed the cohort from January 2000 through December 2008, for a total of 5.6 million patient-years of follow-up. During this period, 3,718 patients were hospitalized for acute MI, including 463 patients with gout. Of these events, 299 were fatal, including 35 in gout patients, Dr. Kuo said. "The incidence of acute [MI] in gout patients was 2.20 per 1,000 patient years and was significantly higher than in nongout patients, which was 0.60," he said.

In the multivariate model adjusted for age, sex, diabetes, hypertension, coronary heart disease, stroke, and end-stage renal disease, the respective hazard ratios for all acute MI and nonfatal acute MI in gout patients were 1.23 and 1.26, Dr. Kuo reported. "In patients without cardiovascular risk factors, the hazard ratio for all acute [MI] was 1.84, and for nonfatal acute [MI] was 1.80," he said, and when assessed by age, the respective hazard ratios for gout patients aged 20-44 years, 45-59 years, and 60 years or older were 1.59, 1.24, and 1.11.

The multivariate model was not adjusted for hyperlipidemia, which has been associated with gout, Dr. Kuo said, acknowledging that elevated lipid levels could play an important role in the increased cardiovascular risks observed in the gout patients.

Although the increased risk of acute MI associated with gout has been previously reported, "the risk in younger patients and those with low risk profiles hasn’t previously been established," Dr. Kuo explained. The finding that gout is an independent risk factor for the occurrence of acute MI – particularly nonfatal acute MI – among young, low-risk patients suggests the need for "vigilant cardiovascular monitoring" of these patients, he stressed.

Dr. Kuo reported having no conflicts of interest to disclose.

LONDON – Gout is an independent risk factor for acute myocardial infarction, even among younger patients and those without cardiovascular risk factors, according to Dr. Chang-Fu Kuo, who presented a late-breaking report at the Annual European Congress of Rheumatology.

The risk for acute MI was 23% higher among gout patients than the general population, judging from an analysis of a large Taiwanese database. Among individuals aged 20-44 years old and those without additional cardiovascular risk factors, the risk of acute MI was increased by 59% and 76%, respectively, reported Dr. Kuo of Chang Gung Memorial Hospital, Taipei, Taiwan.

To investigate the risk of acute MI associated with gout, Dr. Kuo and colleagues analyzed the 2000 Taiwan National Health Insurance database, which is a representative sampling cohort of the general population. Specifically, the investigators compared rates of first hospital admission for acute MI among gout and nongout patients aged 20 years or older. Of the 704,503 individuals included in the cohort (mean age, 42.73 years), 26,566 were diagnosed and treated for gout in 1996-1999, Dr. Kuo said. Compared with the nongout patients, "the gout patients were significantly older, with a mean age of 55.4 years, and they were significantly more likely to have diabetes and hypertension," he said.

The investigators followed the cohort from January 2000 through December 2008, for a total of 5.6 million patient-years of follow-up. During this period, 3,718 patients were hospitalized for acute MI, including 463 patients with gout. Of these events, 299 were fatal, including 35 in gout patients, Dr. Kuo said. "The incidence of acute [MI] in gout patients was 2.20 per 1,000 patient years and was significantly higher than in nongout patients, which was 0.60," he said.

In the multivariate model adjusted for age, sex, diabetes, hypertension, coronary heart disease, stroke, and end-stage renal disease, the respective hazard ratios for all acute MI and nonfatal acute MI in gout patients were 1.23 and 1.26, Dr. Kuo reported. "In patients without cardiovascular risk factors, the hazard ratio for all acute [MI] was 1.84, and for nonfatal acute [MI] was 1.80," he said, and when assessed by age, the respective hazard ratios for gout patients aged 20-44 years, 45-59 years, and 60 years or older were 1.59, 1.24, and 1.11.

The multivariate model was not adjusted for hyperlipidemia, which has been associated with gout, Dr. Kuo said, acknowledging that elevated lipid levels could play an important role in the increased cardiovascular risks observed in the gout patients.

Although the increased risk of acute MI associated with gout has been previously reported, "the risk in younger patients and those with low risk profiles hasn’t previously been established," Dr. Kuo explained. The finding that gout is an independent risk factor for the occurrence of acute MI – particularly nonfatal acute MI – among young, low-risk patients suggests the need for "vigilant cardiovascular monitoring" of these patients, he stressed.

Dr. Kuo reported having no conflicts of interest to disclose.

LONDON – Gout is an independent risk factor for acute myocardial infarction, even among younger patients and those without cardiovascular risk factors, according to Dr. Chang-Fu Kuo, who presented a late-breaking report at the Annual European Congress of Rheumatology.

The risk for acute MI was 23% higher among gout patients than the general population, judging from an analysis of a large Taiwanese database. Among individuals aged 20-44 years old and those without additional cardiovascular risk factors, the risk of acute MI was increased by 59% and 76%, respectively, reported Dr. Kuo of Chang Gung Memorial Hospital, Taipei, Taiwan.

To investigate the risk of acute MI associated with gout, Dr. Kuo and colleagues analyzed the 2000 Taiwan National Health Insurance database, which is a representative sampling cohort of the general population. Specifically, the investigators compared rates of first hospital admission for acute MI among gout and nongout patients aged 20 years or older. Of the 704,503 individuals included in the cohort (mean age, 42.73 years), 26,566 were diagnosed and treated for gout in 1996-1999, Dr. Kuo said. Compared with the nongout patients, "the gout patients were significantly older, with a mean age of 55.4 years, and they were significantly more likely to have diabetes and hypertension," he said.

The investigators followed the cohort from January 2000 through December 2008, for a total of 5.6 million patient-years of follow-up. During this period, 3,718 patients were hospitalized for acute MI, including 463 patients with gout. Of these events, 299 were fatal, including 35 in gout patients, Dr. Kuo said. "The incidence of acute [MI] in gout patients was 2.20 per 1,000 patient years and was significantly higher than in nongout patients, which was 0.60," he said.

In the multivariate model adjusted for age, sex, diabetes, hypertension, coronary heart disease, stroke, and end-stage renal disease, the respective hazard ratios for all acute MI and nonfatal acute MI in gout patients were 1.23 and 1.26, Dr. Kuo reported. "In patients without cardiovascular risk factors, the hazard ratio for all acute [MI] was 1.84, and for nonfatal acute [MI] was 1.80," he said, and when assessed by age, the respective hazard ratios for gout patients aged 20-44 years, 45-59 years, and 60 years or older were 1.59, 1.24, and 1.11.

The multivariate model was not adjusted for hyperlipidemia, which has been associated with gout, Dr. Kuo said, acknowledging that elevated lipid levels could play an important role in the increased cardiovascular risks observed in the gout patients.

Although the increased risk of acute MI associated with gout has been previously reported, "the risk in younger patients and those with low risk profiles hasn’t previously been established," Dr. Kuo explained. The finding that gout is an independent risk factor for the occurrence of acute MI – particularly nonfatal acute MI – among young, low-risk patients suggests the need for "vigilant cardiovascular monitoring" of these patients, he stressed.

Dr. Kuo reported having no conflicts of interest to disclose.

Major Finding: The HPV vaccine does not exacerbate disease activity in women with SLE. The baseline, 3-month, and 6-month measures of disease activity were: C3: 0.79, 0.80, and 0.81 g/dL; C4: 0.15, 0.15, and 0.15 g/dL; anti-dsDNA: 131, 130, and 139 IU/mL; SLEDAI: 3.4, 3.4, and 3.0; and PGA: 0.26, 0.28, and 0.22.

Data Source: A prospective study of 50 female SLE patients and an unvaccinated cohort of SLE patients who were observed over a 5-year period at the same institution.

Disclosures: Dr. Mok disclosed having no financial conflicts of interest.

LONDON – The quadrivalent human papillomavirus vaccine is safe for patients with systemic lupus erythematosus and should be considered for women with inactive disease who receive stable doses of standard immunomodulatory therapy, according to Dr. Chi Chiu Mok.

Multiple studies have demonstrated higher rates of persistent HPV infections and precancerous lesions in women with SLE, compared with women in the general population, said Dr. Mok.

It has been hypothesized that immune dysfunction related to SLE or to treatment-induced immune suppression may prevent patients with the condition from being able to produce an effective immune response to the vaccine, and could possibly lead to disease flares or the production of new autoantibodies, Dr. Mo explained.

The recombinant quadrivalent HPV vaccine (Gardisil) provides protection against infection of the HPV serotypes 6, 11, 16, and 18, and it has been demonstrated to be safe and efficacious in female patients in the general population aged 9-26 years, according to Dr. Mok. Along with colleagues at Tuen Mun Hospital in Hong Kong, Dr. Mok evaluated the vaccine's safety and immunogen-icity in a cohort of SLE patients.

Toward this end, the investigators recruited 50 female patients aged 18–35 years who fulfilled at least four American College of Rheumatology criteria for SLE, and who had received a stable dose of prednisolone or other immunosuppressive agent within the previous 3 months, to participate in the prospective investigation. The mean age of the study participants was 25.8 years, and their mean disease duration was 6.6 years, he reported.

All of the study subjects received intramuscular injections of the vaccine and were evaluated at baseline and at 2 and 6 months post vaccination via the SLEDAI (SLE Disease Activity Index), PGA (Physicians' Global Assessment), and the SELENA (Safety of Estrogens in Lupus Erythematosus – National Assessment) disease flare index. Additionally, complement levels (C3 and C4) and anti-dsDNA (anti–double-stranded DNA) titers were assessed and patient-reported adverse events were recorded at the same time points, said Dr. Mok. With respect to baseline disease characteristics, the median SLEDAI score was 4; the mean anti-dsDNA titers, C3 levels, and C4 levels were 139 IU/mL, 0.81 g/dL, and 0.15 g/dL, respectively; and none of the patients had SELENA flares at baseline compared to preceding status, he said.

There were no significant changes in anti-dsDNA titers, C3 or C4 levels, or SLEDAI and PGA scores at any of the time points, Dr. Mok reported. Specifically, the baseline, 3-month, and 6-month measures of disease activity were: C3: 0.79, 0.80, and 0.81 g/dL; C4: 0.15, 0.15, and 0.15 g/dL; anti-dsDNA: 131, 130, and 139 IU/mL; SLEDAI: 3.4, 3.4, and 3.0; and PGA: 0.26, 0.28, and 0.22. “There were three mild to moderate mucocutaneous flares during the study period (one at month 2 and two at month 6), all of which were controlled with usual treatment,” he said.

“It's unclear whether a causal relationship exists between the vaccination and the three lupus flares, but the rate of flares [0.08 per patient per year] was lower than the rate observed in our lupus cohort during the previous 5 years [0.10 per patient per year], and no other adverse events associated with the vaccination were reported.”

The study findings indicate that the vaccine is safe in SLE patients, and the lack of significant alterations in the various SLE antibody measures suggests it does not induce an increased incidence of lupus flares, Dr. Mok stated.

Major Finding: The HPV vaccine does not exacerbate disease activity in women with SLE. The baseline, 3-month, and 6-month measures of disease activity were: C3: 0.79, 0.80, and 0.81 g/dL; C4: 0.15, 0.15, and 0.15 g/dL; anti-dsDNA: 131, 130, and 139 IU/mL; SLEDAI: 3.4, 3.4, and 3.0; and PGA: 0.26, 0.28, and 0.22.

Data Source: A prospective study of 50 female SLE patients and an unvaccinated cohort of SLE patients who were observed over a 5-year period at the same institution.

Disclosures: Dr. Mok disclosed having no financial conflicts of interest.

LONDON – The quadrivalent human papillomavirus vaccine is safe for patients with systemic lupus erythematosus and should be considered for women with inactive disease who receive stable doses of standard immunomodulatory therapy, according to Dr. Chi Chiu Mok.

Multiple studies have demonstrated higher rates of persistent HPV infections and precancerous lesions in women with SLE, compared with women in the general population, said Dr. Mok.

It has been hypothesized that immune dysfunction related to SLE or to treatment-induced immune suppression may prevent patients with the condition from being able to produce an effective immune response to the vaccine, and could possibly lead to disease flares or the production of new autoantibodies, Dr. Mo explained.

The recombinant quadrivalent HPV vaccine (Gardisil) provides protection against infection of the HPV serotypes 6, 11, 16, and 18, and it has been demonstrated to be safe and efficacious in female patients in the general population aged 9-26 years, according to Dr. Mok. Along with colleagues at Tuen Mun Hospital in Hong Kong, Dr. Mok evaluated the vaccine's safety and immunogen-icity in a cohort of SLE patients.

Toward this end, the investigators recruited 50 female patients aged 18–35 years who fulfilled at least four American College of Rheumatology criteria for SLE, and who had received a stable dose of prednisolone or other immunosuppressive agent within the previous 3 months, to participate in the prospective investigation. The mean age of the study participants was 25.8 years, and their mean disease duration was 6.6 years, he reported.

All of the study subjects received intramuscular injections of the vaccine and were evaluated at baseline and at 2 and 6 months post vaccination via the SLEDAI (SLE Disease Activity Index), PGA (Physicians' Global Assessment), and the SELENA (Safety of Estrogens in Lupus Erythematosus – National Assessment) disease flare index. Additionally, complement levels (C3 and C4) and anti-dsDNA (anti–double-stranded DNA) titers were assessed and patient-reported adverse events were recorded at the same time points, said Dr. Mok. With respect to baseline disease characteristics, the median SLEDAI score was 4; the mean anti-dsDNA titers, C3 levels, and C4 levels were 139 IU/mL, 0.81 g/dL, and 0.15 g/dL, respectively; and none of the patients had SELENA flares at baseline compared to preceding status, he said.

There were no significant changes in anti-dsDNA titers, C3 or C4 levels, or SLEDAI and PGA scores at any of the time points, Dr. Mok reported. Specifically, the baseline, 3-month, and 6-month measures of disease activity were: C3: 0.79, 0.80, and 0.81 g/dL; C4: 0.15, 0.15, and 0.15 g/dL; anti-dsDNA: 131, 130, and 139 IU/mL; SLEDAI: 3.4, 3.4, and 3.0; and PGA: 0.26, 0.28, and 0.22. “There were three mild to moderate mucocutaneous flares during the study period (one at month 2 and two at month 6), all of which were controlled with usual treatment,” he said.

“It's unclear whether a causal relationship exists between the vaccination and the three lupus flares, but the rate of flares [0.08 per patient per year] was lower than the rate observed in our lupus cohort during the previous 5 years [0.10 per patient per year], and no other adverse events associated with the vaccination were reported.”

The study findings indicate that the vaccine is safe in SLE patients, and the lack of significant alterations in the various SLE antibody measures suggests it does not induce an increased incidence of lupus flares, Dr. Mok stated.

Major Finding: The HPV vaccine does not exacerbate disease activity in women with SLE. The baseline, 3-month, and 6-month measures of disease activity were: C3: 0.79, 0.80, and 0.81 g/dL; C4: 0.15, 0.15, and 0.15 g/dL; anti-dsDNA: 131, 130, and 139 IU/mL; SLEDAI: 3.4, 3.4, and 3.0; and PGA: 0.26, 0.28, and 0.22.

Data Source: A prospective study of 50 female SLE patients and an unvaccinated cohort of SLE patients who were observed over a 5-year period at the same institution.

Disclosures: Dr. Mok disclosed having no financial conflicts of interest.

LONDON – The quadrivalent human papillomavirus vaccine is safe for patients with systemic lupus erythematosus and should be considered for women with inactive disease who receive stable doses of standard immunomodulatory therapy, according to Dr. Chi Chiu Mok.

Multiple studies have demonstrated higher rates of persistent HPV infections and precancerous lesions in women with SLE, compared with women in the general population, said Dr. Mok.

It has been hypothesized that immune dysfunction related to SLE or to treatment-induced immune suppression may prevent patients with the condition from being able to produce an effective immune response to the vaccine, and could possibly lead to disease flares or the production of new autoantibodies, Dr. Mo explained.

The recombinant quadrivalent HPV vaccine (Gardisil) provides protection against infection of the HPV serotypes 6, 11, 16, and 18, and it has been demonstrated to be safe and efficacious in female patients in the general population aged 9-26 years, according to Dr. Mok. Along with colleagues at Tuen Mun Hospital in Hong Kong, Dr. Mok evaluated the vaccine's safety and immunogen-icity in a cohort of SLE patients.

Toward this end, the investigators recruited 50 female patients aged 18–35 years who fulfilled at least four American College of Rheumatology criteria for SLE, and who had received a stable dose of prednisolone or other immunosuppressive agent within the previous 3 months, to participate in the prospective investigation. The mean age of the study participants was 25.8 years, and their mean disease duration was 6.6 years, he reported.

All of the study subjects received intramuscular injections of the vaccine and were evaluated at baseline and at 2 and 6 months post vaccination via the SLEDAI (SLE Disease Activity Index), PGA (Physicians' Global Assessment), and the SELENA (Safety of Estrogens in Lupus Erythematosus – National Assessment) disease flare index. Additionally, complement levels (C3 and C4) and anti-dsDNA (anti–double-stranded DNA) titers were assessed and patient-reported adverse events were recorded at the same time points, said Dr. Mok. With respect to baseline disease characteristics, the median SLEDAI score was 4; the mean anti-dsDNA titers, C3 levels, and C4 levels were 139 IU/mL, 0.81 g/dL, and 0.15 g/dL, respectively; and none of the patients had SELENA flares at baseline compared to preceding status, he said.

There were no significant changes in anti-dsDNA titers, C3 or C4 levels, or SLEDAI and PGA scores at any of the time points, Dr. Mok reported. Specifically, the baseline, 3-month, and 6-month measures of disease activity were: C3: 0.79, 0.80, and 0.81 g/dL; C4: 0.15, 0.15, and 0.15 g/dL; anti-dsDNA: 131, 130, and 139 IU/mL; SLEDAI: 3.4, 3.4, and 3.0; and PGA: 0.26, 0.28, and 0.22. “There were three mild to moderate mucocutaneous flares during the study period (one at month 2 and two at month 6), all of which were controlled with usual treatment,” he said.

“It's unclear whether a causal relationship exists between the vaccination and the three lupus flares, but the rate of flares [0.08 per patient per year] was lower than the rate observed in our lupus cohort during the previous 5 years [0.10 per patient per year], and no other adverse events associated with the vaccination were reported.”

The study findings indicate that the vaccine is safe in SLE patients, and the lack of significant alterations in the various SLE antibody measures suggests it does not induce an increased incidence of lupus flares, Dr. Mok stated.

Major Finding: The RA and diabetes cohorts both had a 1.7 increased incidence rate ratio (IRR) of MI, compared with the general population.

Data Source: A large, population-based study of the incidence of new-onset rheumatoid arthritis, diabetes, and myocardial infarction using Danish patient registry information covering a 10-year period.

Disclosures: The study was supported by an unrestricted grant from the Danish Rheumatism Association. The authors disclosed having no conflicts of interest.

The cardiovascular risk in rheumatoid arthritis is comparable to that of diabetes, a large Danish study has shown.

Further, the risk of myocardial infarction (MI) in rheumatoid arthritis patients corresponds to that observed in the general population of individuals without the musculoskeletal condition who are, on average, 10 years older and does not appear to be affected by the duration of drug treatment for the disease, Dr. Jesper Lindhardsen of Gentofte University Hospital in Copenhagen, and colleagues reported.

Using nationwide registers encompassing the entire Danish population older than 16 years, the investigators identified individuals with new-onset rheumatoid arthritis (RA), new-onset diabetes, and new MI during a 10-year period, excluding individuals with prior disease and incomplete data entries from the full cohort of 4,311,022 subjects, they wrote.

During the 10-year study period, 9,921 individuals developed RA and 129,659 developed diabetes. Compared with the diabetes patients, “RA patients were more often women, used less cardioprotective medications, and had less comorbidity, whereas age was similar in the two groups,” they reported.

Regarding cardiovascular outcomes, 265 of the RA patients and 3,948 of the diabetes patients had new MI, representing in both cohorts a 1.7 increased incidence rate ratio (IRR) of MI in a fully adjusted model compared with the general population in which 75,870 individuals had new myocardial infarctions. The IRR among patients with both RA and diabetes was 2.6, “which roughly equaled the predicted additive risk for the two separate diseases, they wrote (Ann. Rheum. Dis. 2011;70:929–34).

The investigators conducted a nested case-control study that corroborated the comparable risk of MI in the RA and diabetes patients. The findings demonstrated that the increased risk in these groups was independent of treatment duration within the time frame of the current study, they wrote.

Stratified by gender, the MI risk estimates did not differ between women and men in the RA group. In the diabetes patients, however, women were at significantly higher risk than men for the adverse cardiovascular outcome, the authors wrote. An age-dependent pattern of MI risk was also observed. Specifically, among women with RA and diabetes, respectively, the risk of MI in those younger than 50 years old was 5.5 and 5.9 times that observed in the age-matched reference group, they reported. Additionally, for women between 50 and 65 years of age, the IRRs were 1.7 and 2.6 for RA and diabetes patients, respectively.

The age-stratified patterns observed in men were different, the authors stated, noting that “the IRRs in the two oldest age groups were comparable, and even tended to be slightly higher in the 50-65 years age group of RA patients compared to the same-aged [diabetes] patients.” And while the youngest men with RA had a markedly raised IRR, diabetes patients in the same age stratum had a significantly higher risk, with an IRR of 4.9 compared with 2.1, they said.

In a fully adjusted regression model in which the IRRs for MI in RA patients were calculated according to 10-year subject age intervals, “RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older,” the authors reported.

Although the study has several limitations, including the identification of RA patients based on dispensed prescriptions and diagnosis versus the 1987 American College of Rheumatology criteria, the reliance on the use of glucose-lowering drugs as a proxy for diabetes, and the lack of information about classic cardiovascular risk factors, “the results corroborate and expand previous findings in this area of research and indicate that patients with RA should be considered for more aggressive primary [cardiovascular disease] prevention,” the authors stressed.

In an accompanying editorial, Dr. Michael T. Nurmohamed and Dr. George Kitas of VU University Medical Centre in Amsterdam wrote that the findings of the current study should put to bed any doubt or debate about an enhanced cardiovascular risk in RA. “Importantly, they also provide further evidence that the cardiovascular risk in RA is broadly similar to that of contemporarily managed diabetes,” they stated. The results of the study, as well as the success of cardiovascular risk management in diabetes provides a clear incentive to identify and actively manage, if necessary, cardiovascular risk in all RA patients as part of quality routine rheumatological practice” (Ann. Rheum. Dis. 2011;70:881–3).

The study was sponsored by an unrestricted grant from the Danish Rheumatism Association. The authors of the study and the accompanying editorial reported having no conflicts of interest.

'RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older.'

Source DR. LINDHARDSEN

Major Finding: The RA and diabetes cohorts both had a 1.7 increased incidence rate ratio (IRR) of MI, compared with the general population.

Data Source: A large, population-based study of the incidence of new-onset rheumatoid arthritis, diabetes, and myocardial infarction using Danish patient registry information covering a 10-year period.

Disclosures: The study was supported by an unrestricted grant from the Danish Rheumatism Association. The authors disclosed having no conflicts of interest.

The cardiovascular risk in rheumatoid arthritis is comparable to that of diabetes, a large Danish study has shown.

Further, the risk of myocardial infarction (MI) in rheumatoid arthritis patients corresponds to that observed in the general population of individuals without the musculoskeletal condition who are, on average, 10 years older and does not appear to be affected by the duration of drug treatment for the disease, Dr. Jesper Lindhardsen of Gentofte University Hospital in Copenhagen, and colleagues reported.

Using nationwide registers encompassing the entire Danish population older than 16 years, the investigators identified individuals with new-onset rheumatoid arthritis (RA), new-onset diabetes, and new MI during a 10-year period, excluding individuals with prior disease and incomplete data entries from the full cohort of 4,311,022 subjects, they wrote.

During the 10-year study period, 9,921 individuals developed RA and 129,659 developed diabetes. Compared with the diabetes patients, “RA patients were more often women, used less cardioprotective medications, and had less comorbidity, whereas age was similar in the two groups,” they reported.

Regarding cardiovascular outcomes, 265 of the RA patients and 3,948 of the diabetes patients had new MI, representing in both cohorts a 1.7 increased incidence rate ratio (IRR) of MI in a fully adjusted model compared with the general population in which 75,870 individuals had new myocardial infarctions. The IRR among patients with both RA and diabetes was 2.6, “which roughly equaled the predicted additive risk for the two separate diseases, they wrote (Ann. Rheum. Dis. 2011;70:929–34).

The investigators conducted a nested case-control study that corroborated the comparable risk of MI in the RA and diabetes patients. The findings demonstrated that the increased risk in these groups was independent of treatment duration within the time frame of the current study, they wrote.

Stratified by gender, the MI risk estimates did not differ between women and men in the RA group. In the diabetes patients, however, women were at significantly higher risk than men for the adverse cardiovascular outcome, the authors wrote. An age-dependent pattern of MI risk was also observed. Specifically, among women with RA and diabetes, respectively, the risk of MI in those younger than 50 years old was 5.5 and 5.9 times that observed in the age-matched reference group, they reported. Additionally, for women between 50 and 65 years of age, the IRRs were 1.7 and 2.6 for RA and diabetes patients, respectively.

The age-stratified patterns observed in men were different, the authors stated, noting that “the IRRs in the two oldest age groups were comparable, and even tended to be slightly higher in the 50-65 years age group of RA patients compared to the same-aged [diabetes] patients.” And while the youngest men with RA had a markedly raised IRR, diabetes patients in the same age stratum had a significantly higher risk, with an IRR of 4.9 compared with 2.1, they said.

In a fully adjusted regression model in which the IRRs for MI in RA patients were calculated according to 10-year subject age intervals, “RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older,” the authors reported.

Although the study has several limitations, including the identification of RA patients based on dispensed prescriptions and diagnosis versus the 1987 American College of Rheumatology criteria, the reliance on the use of glucose-lowering drugs as a proxy for diabetes, and the lack of information about classic cardiovascular risk factors, “the results corroborate and expand previous findings in this area of research and indicate that patients with RA should be considered for more aggressive primary [cardiovascular disease] prevention,” the authors stressed.

In an accompanying editorial, Dr. Michael T. Nurmohamed and Dr. George Kitas of VU University Medical Centre in Amsterdam wrote that the findings of the current study should put to bed any doubt or debate about an enhanced cardiovascular risk in RA. “Importantly, they also provide further evidence that the cardiovascular risk in RA is broadly similar to that of contemporarily managed diabetes,” they stated. The results of the study, as well as the success of cardiovascular risk management in diabetes provides a clear incentive to identify and actively manage, if necessary, cardiovascular risk in all RA patients as part of quality routine rheumatological practice” (Ann. Rheum. Dis. 2011;70:881–3).

The study was sponsored by an unrestricted grant from the Danish Rheumatism Association. The authors of the study and the accompanying editorial reported having no conflicts of interest.

'RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older.'

Source DR. LINDHARDSEN

Major Finding: The RA and diabetes cohorts both had a 1.7 increased incidence rate ratio (IRR) of MI, compared with the general population.

Data Source: A large, population-based study of the incidence of new-onset rheumatoid arthritis, diabetes, and myocardial infarction using Danish patient registry information covering a 10-year period.

Disclosures: The study was supported by an unrestricted grant from the Danish Rheumatism Association. The authors disclosed having no conflicts of interest.

The cardiovascular risk in rheumatoid arthritis is comparable to that of diabetes, a large Danish study has shown.

Further, the risk of myocardial infarction (MI) in rheumatoid arthritis patients corresponds to that observed in the general population of individuals without the musculoskeletal condition who are, on average, 10 years older and does not appear to be affected by the duration of drug treatment for the disease, Dr. Jesper Lindhardsen of Gentofte University Hospital in Copenhagen, and colleagues reported.

Using nationwide registers encompassing the entire Danish population older than 16 years, the investigators identified individuals with new-onset rheumatoid arthritis (RA), new-onset diabetes, and new MI during a 10-year period, excluding individuals with prior disease and incomplete data entries from the full cohort of 4,311,022 subjects, they wrote.

During the 10-year study period, 9,921 individuals developed RA and 129,659 developed diabetes. Compared with the diabetes patients, “RA patients were more often women, used less cardioprotective medications, and had less comorbidity, whereas age was similar in the two groups,” they reported.

Regarding cardiovascular outcomes, 265 of the RA patients and 3,948 of the diabetes patients had new MI, representing in both cohorts a 1.7 increased incidence rate ratio (IRR) of MI in a fully adjusted model compared with the general population in which 75,870 individuals had new myocardial infarctions. The IRR among patients with both RA and diabetes was 2.6, “which roughly equaled the predicted additive risk for the two separate diseases, they wrote (Ann. Rheum. Dis. 2011;70:929–34).

The investigators conducted a nested case-control study that corroborated the comparable risk of MI in the RA and diabetes patients. The findings demonstrated that the increased risk in these groups was independent of treatment duration within the time frame of the current study, they wrote.

Stratified by gender, the MI risk estimates did not differ between women and men in the RA group. In the diabetes patients, however, women were at significantly higher risk than men for the adverse cardiovascular outcome, the authors wrote. An age-dependent pattern of MI risk was also observed. Specifically, among women with RA and diabetes, respectively, the risk of MI in those younger than 50 years old was 5.5 and 5.9 times that observed in the age-matched reference group, they reported. Additionally, for women between 50 and 65 years of age, the IRRs were 1.7 and 2.6 for RA and diabetes patients, respectively.

The age-stratified patterns observed in men were different, the authors stated, noting that “the IRRs in the two oldest age groups were comparable, and even tended to be slightly higher in the 50-65 years age group of RA patients compared to the same-aged [diabetes] patients.” And while the youngest men with RA had a markedly raised IRR, diabetes patients in the same age stratum had a significantly higher risk, with an IRR of 4.9 compared with 2.1, they said.

In a fully adjusted regression model in which the IRRs for MI in RA patients were calculated according to 10-year subject age intervals, “RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older,” the authors reported.

Although the study has several limitations, including the identification of RA patients based on dispensed prescriptions and diagnosis versus the 1987 American College of Rheumatology criteria, the reliance on the use of glucose-lowering drugs as a proxy for diabetes, and the lack of information about classic cardiovascular risk factors, “the results corroborate and expand previous findings in this area of research and indicate that patients with RA should be considered for more aggressive primary [cardiovascular disease] prevention,” the authors stressed.

In an accompanying editorial, Dr. Michael T. Nurmohamed and Dr. George Kitas of VU University Medical Centre in Amsterdam wrote that the findings of the current study should put to bed any doubt or debate about an enhanced cardiovascular risk in RA. “Importantly, they also provide further evidence that the cardiovascular risk in RA is broadly similar to that of contemporarily managed diabetes,” they stated. The results of the study, as well as the success of cardiovascular risk management in diabetes provides a clear incentive to identify and actively manage, if necessary, cardiovascular risk in all RA patients as part of quality routine rheumatological practice” (Ann. Rheum. Dis. 2011;70:881–3).

The study was sponsored by an unrestricted grant from the Danish Rheumatism Association. The authors of the study and the accompanying editorial reported having no conflicts of interest.

'RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older.'

Source DR. LINDHARDSEN

The cardiovascular risk in rheumatoid arthritis is comparable to that of diabetes, a large Danish study has shown.

Further, the risk of myocardial infarction (MI) in rheumatoid arthritis patients corresponds to that observed in the general population of individuals without the musculoskeletal condition who are, on average, 10 years older and does not appear to be affected by the duration of drug treatment for the disease, Dr. Jesper Lindhardsen of Gentofte University Hospital in Copenhagen, Denmark, and colleagues reported.

Using nationwide registers encompassing the entire Danish population older than 16 years, the investigators identified individuals with new-onset rheumatoid arthritis (RA), new onset diabetes, and new MI during a 10-year period, excluding individuals with prior disease and incomplete data entries from the full cohort of 4,311,022 subjects, they wrote.

During the 10-year study period, 9,921 individuals developed RA and 129,659 developed diabetes, the authors reported. Compared with the diabetes patients, "RA patients were more often women, used less cardioprotective medications, and had less comorbidity, whereas age was similar in the two groups," they reported.

Regarding cardiovascular outcomes, 265 of the RA patients and 3,948 of the diabetes patients had new MI, representing in both cohorts a 1.7 increased incidence rate ratio (IRR) of MI in a fully adjusted model compared with the general population in which 75,870 individuals had new myocardial infarctions, they wrote. The IRR among patients with both RA and diabetes was 2.6, "which roughly equaled the predicted additive risk for the two separate diseases, they wrote (Ann. Rheum. Dis. 2011;70:929-34).

The investigators conducted a nested case-control study that corroborated the comparable risk of MI in the RA and diabetes patients. The findings demonstrated that the increased risk in these groups was independent of treatment duration within the timeframe of the current study, they wrote.

Stratified by gender, the MI risk estimates did not differ between women and men in the RA group. In the diabetes patients, however, women were at significantly higher risk than men for the adverse cardiovascular outcome, the authors wrote. An age-dependent pattern of MI risk was also observed. Specifically, among women with RA and diabetes, respectively, the risk of MI in those younger than 50 years old was 5.5 and 5.9 times that observed in the age-matched reference group, they reported. Additionally, for women between 50 and 65 years of age, the IRRs were 1.7 and 2.6 for RA and diabetes patients, respectively.

The age-stratified patterns observed in men were different, the authors stated, noting that "the IRRs in the two oldest age groups were comparable, and even tended to be slightly higher in the 50-65 years age group of RA patients compared to the same-aged [diabetes] patients." And while the youngest men with RA had a markedly raised IRR, diabetes patients in the same age stratum had a significantly higher risk, with an IRR of 4.9 compared with 2.1, they said.

In a fully adjusted regression model in which the IRRs for MI in RA patients were calculated according to 10-year subject age intervals, "RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older," the authors reported.

Although the study has several limitations, including the identification of RA patients based on dispensed prescriptions and diagnosis versus the 1987 American College of Rheumatology criteria, the reliance on the use of glucose-lowering drugs as a proxy for diabetes, and the lack of information about classic cardiovascular risk factors, "the results corroborate and expand previous findings in this area of research and indicate that patients with RA should be considered for more aggressive primary [cardiovascular disease] prevention," the authors stressed.

In an accompanying editorial, Dr. Michael T. Nurmohamed and Dr. George Kitas of VU University Medical Centre in Amsterdam wrote that the findings of the current study should put to bed any doubt or debate about an enhanced cardiovascular risk in RA. "Importantly, they also provide further evidence that the cardiovascular risk in RA is broadly similar to that of contemporarily managed diabetes," they stated. The results of the study, as well as the success of cardiovascular risk management in diabetes provides a clear incentive to identify and actively manage, if necessary, cardiovascular risk in all RA patients as part of quality routine rheumatological practice" (Ann. Rheum. Dis. 2011;70:881-3).

The study was sponsored by an unrestricted grant from the Danish Rheumatism Association. The authors of the study and the accompanying editorial reported having no conflicts of interest to disclose.

The cardiovascular risk in rheumatoid arthritis is comparable to that of diabetes, a large Danish study has shown.

Further, the risk of myocardial infarction (MI) in rheumatoid arthritis patients corresponds to that observed in the general population of individuals without the musculoskeletal condition who are, on average, 10 years older and does not appear to be affected by the duration of drug treatment for the disease, Dr. Jesper Lindhardsen of Gentofte University Hospital in Copenhagen, Denmark, and colleagues reported.

Using nationwide registers encompassing the entire Danish population older than 16 years, the investigators identified individuals with new-onset rheumatoid arthritis (RA), new onset diabetes, and new MI during a 10-year period, excluding individuals with prior disease and incomplete data entries from the full cohort of 4,311,022 subjects, they wrote.

During the 10-year study period, 9,921 individuals developed RA and 129,659 developed diabetes, the authors reported. Compared with the diabetes patients, "RA patients were more often women, used less cardioprotective medications, and had less comorbidity, whereas age was similar in the two groups," they reported.

Regarding cardiovascular outcomes, 265 of the RA patients and 3,948 of the diabetes patients had new MI, representing in both cohorts a 1.7 increased incidence rate ratio (IRR) of MI in a fully adjusted model compared with the general population in which 75,870 individuals had new myocardial infarctions, they wrote. The IRR among patients with both RA and diabetes was 2.6, "which roughly equaled the predicted additive risk for the two separate diseases, they wrote (Ann. Rheum. Dis. 2011;70:929-34).

The investigators conducted a nested case-control study that corroborated the comparable risk of MI in the RA and diabetes patients. The findings demonstrated that the increased risk in these groups was independent of treatment duration within the timeframe of the current study, they wrote.

Stratified by gender, the MI risk estimates did not differ between women and men in the RA group. In the diabetes patients, however, women were at significantly higher risk than men for the adverse cardiovascular outcome, the authors wrote. An age-dependent pattern of MI risk was also observed. Specifically, among women with RA and diabetes, respectively, the risk of MI in those younger than 50 years old was 5.5 and 5.9 times that observed in the age-matched reference group, they reported. Additionally, for women between 50 and 65 years of age, the IRRs were 1.7 and 2.6 for RA and diabetes patients, respectively.

The age-stratified patterns observed in men were different, the authors stated, noting that "the IRRs in the two oldest age groups were comparable, and even tended to be slightly higher in the 50-65 years age group of RA patients compared to the same-aged [diabetes] patients." And while the youngest men with RA had a markedly raised IRR, diabetes patients in the same age stratum had a significantly higher risk, with an IRR of 4.9 compared with 2.1, they said.

In a fully adjusted regression model in which the IRRs for MI in RA patients were calculated according to 10-year subject age intervals, "RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older," the authors reported.

Although the study has several limitations, including the identification of RA patients based on dispensed prescriptions and diagnosis versus the 1987 American College of Rheumatology criteria, the reliance on the use of glucose-lowering drugs as a proxy for diabetes, and the lack of information about classic cardiovascular risk factors, "the results corroborate and expand previous findings in this area of research and indicate that patients with RA should be considered for more aggressive primary [cardiovascular disease] prevention," the authors stressed.

In an accompanying editorial, Dr. Michael T. Nurmohamed and Dr. George Kitas of VU University Medical Centre in Amsterdam wrote that the findings of the current study should put to bed any doubt or debate about an enhanced cardiovascular risk in RA. "Importantly, they also provide further evidence that the cardiovascular risk in RA is broadly similar to that of contemporarily managed diabetes," they stated. The results of the study, as well as the success of cardiovascular risk management in diabetes provides a clear incentive to identify and actively manage, if necessary, cardiovascular risk in all RA patients as part of quality routine rheumatological practice" (Ann. Rheum. Dis. 2011;70:881-3).

The study was sponsored by an unrestricted grant from the Danish Rheumatism Association. The authors of the study and the accompanying editorial reported having no conflicts of interest to disclose.

The cardiovascular risk in rheumatoid arthritis is comparable to that of diabetes, a large Danish study has shown.

Further, the risk of myocardial infarction (MI) in rheumatoid arthritis patients corresponds to that observed in the general population of individuals without the musculoskeletal condition who are, on average, 10 years older and does not appear to be affected by the duration of drug treatment for the disease, Dr. Jesper Lindhardsen of Gentofte University Hospital in Copenhagen, Denmark, and colleagues reported.

Using nationwide registers encompassing the entire Danish population older than 16 years, the investigators identified individuals with new-onset rheumatoid arthritis (RA), new onset diabetes, and new MI during a 10-year period, excluding individuals with prior disease and incomplete data entries from the full cohort of 4,311,022 subjects, they wrote.

During the 10-year study period, 9,921 individuals developed RA and 129,659 developed diabetes, the authors reported. Compared with the diabetes patients, "RA patients were more often women, used less cardioprotective medications, and had less comorbidity, whereas age was similar in the two groups," they reported.

Regarding cardiovascular outcomes, 265 of the RA patients and 3,948 of the diabetes patients had new MI, representing in both cohorts a 1.7 increased incidence rate ratio (IRR) of MI in a fully adjusted model compared with the general population in which 75,870 individuals had new myocardial infarctions, they wrote. The IRR among patients with both RA and diabetes was 2.6, "which roughly equaled the predicted additive risk for the two separate diseases, they wrote (Ann. Rheum. Dis. 2011;70:929-34).

The investigators conducted a nested case-control study that corroborated the comparable risk of MI in the RA and diabetes patients. The findings demonstrated that the increased risk in these groups was independent of treatment duration within the timeframe of the current study, they wrote.

Stratified by gender, the MI risk estimates did not differ between women and men in the RA group. In the diabetes patients, however, women were at significantly higher risk than men for the adverse cardiovascular outcome, the authors wrote. An age-dependent pattern of MI risk was also observed. Specifically, among women with RA and diabetes, respectively, the risk of MI in those younger than 50 years old was 5.5 and 5.9 times that observed in the age-matched reference group, they reported. Additionally, for women between 50 and 65 years of age, the IRRs were 1.7 and 2.6 for RA and diabetes patients, respectively.

The age-stratified patterns observed in men were different, the authors stated, noting that "the IRRs in the two oldest age groups were comparable, and even tended to be slightly higher in the 50-65 years age group of RA patients compared to the same-aged [diabetes] patients." And while the youngest men with RA had a markedly raised IRR, diabetes patients in the same age stratum had a significantly higher risk, with an IRR of 4.9 compared with 2.1, they said.

In a fully adjusted regression model in which the IRRs for MI in RA patients were calculated according to 10-year subject age intervals, "RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older," the authors reported.

Although the study has several limitations, including the identification of RA patients based on dispensed prescriptions and diagnosis versus the 1987 American College of Rheumatology criteria, the reliance on the use of glucose-lowering drugs as a proxy for diabetes, and the lack of information about classic cardiovascular risk factors, "the results corroborate and expand previous findings in this area of research and indicate that patients with RA should be considered for more aggressive primary [cardiovascular disease] prevention," the authors stressed.

In an accompanying editorial, Dr. Michael T. Nurmohamed and Dr. George Kitas of VU University Medical Centre in Amsterdam wrote that the findings of the current study should put to bed any doubt or debate about an enhanced cardiovascular risk in RA. "Importantly, they also provide further evidence that the cardiovascular risk in RA is broadly similar to that of contemporarily managed diabetes," they stated. The results of the study, as well as the success of cardiovascular risk management in diabetes provides a clear incentive to identify and actively manage, if necessary, cardiovascular risk in all RA patients as part of quality routine rheumatological practice" (Ann. Rheum. Dis. 2011;70:881-3).

The study was sponsored by an unrestricted grant from the Danish Rheumatism Association. The authors of the study and the accompanying editorial reported having no conflicts of interest to disclose.