Amy Rothman Schonfeld

NEW YORK – Almost one-third of 132 women with endometriosis had a genetic mutation affecting expression of the KRAS gene, compared with only 5.8% of the general population, according to Dr. Hugh S. Taylor, who presented the findings at the annual congress of the Endometriosis Foundation of America.

"This is the only clearly identified genetic cause of endometriosis," explained Dr. Taylor. The KRAS oncogene produces a protein involved primarily in regulating cell division. The defect found in the women with endometriosis has been localized to a regulatory region of the KRAS gene: the let-7 microRNA (miRNA) binding site in the 3’-untranslated region (UTR).

A high proliferation and invasion rate was seen in endometrial cells from women with the variant allele. These properties may facilitate the invasion of endometrial cells into peritoneum and ovarian cortex.

"This mechanism supports the most accepted theory for the origin of endometriosis – retrograde menstruation and subsequent implantation and invasion of susceptible tissues ... The fact that only a portion of women develop this disease despite the nearly universal occurrence of retrograde menstruation could be explained by the presence of this allele," said Dr. Taylor, director of the division of reproductive endocrinology and infertility at Yale University, New Haven, Conn. The findings were published in the March issue of EMBO Molecular Medicine (EMBO Mol. Med. 2012;4:206-17) (Olga Grechukhina is the first author).

Since the mutation occurs only in a subgroup of women with endometriosis, genetic testing cannot be used as a screening tool. However, the recognition of KRAS-related endometriosis may allow for screening of family members and may have value for personalizing treatment of endometriosis, said Dr. Taylor.

Several lines of evidence reported by Dr. Taylor pinpoint the importance of this genetic mutation. In addition to the clinical observation that 31% of the sample of 132 women with endometriosis had this polymorphism compared with 5.8% of the control population, KRAS mRNA and protein levels were significantly increased in cultured endometrial stromal cells of women with the KRAS variant.

Dr. Taylor also looked at the behavior of endometrial stromal cells from women with and without the variant. Compared with cells from women without endometriosis, cells from women with endometriosis but without the variant were more invasive and proliferative. But cells from women with endometriosis and the variant had even higher levels of invasiveness and proliferation.

In another experiment, cells taken from women with endometriosis were transplanted under the kidney capsules of immunodeficient mice. Cells from the women with the mutation proliferated faster and had a lower expression of the progesterone receptor. "Progesterone resistance is characteristic of some women with endometriosis," commented Dr. Taylor.

Women with the mutation have a much lower expression of all let-7 miRNAs, not just let-7a. "Let-7 doesn’t just bind KRAS – it binds and generally downregulates many genes. When let-7 is inhibited, it no longer stops the expression of many genes involved in mitotic signaling, cell cycling and cell adhesion and migration," explained Dr. Taylor.

Dr. Taylor had no relevant financial disclosures.

NEW YORK – Almost one-third of 132 women with endometriosis had a genetic mutation affecting expression of the KRAS gene, compared with only 5.8% of the general population, according to Dr. Hugh S. Taylor, who presented the findings at the annual congress of the Endometriosis Foundation of America.

"This is the only clearly identified genetic cause of endometriosis," explained Dr. Taylor. The KRAS oncogene produces a protein involved primarily in regulating cell division. The defect found in the women with endometriosis has been localized to a regulatory region of the KRAS gene: the let-7 microRNA (miRNA) binding site in the 3’-untranslated region (UTR).

A high proliferation and invasion rate was seen in endometrial cells from women with the variant allele. These properties may facilitate the invasion of endometrial cells into peritoneum and ovarian cortex.

"This mechanism supports the most accepted theory for the origin of endometriosis – retrograde menstruation and subsequent implantation and invasion of susceptible tissues ... The fact that only a portion of women develop this disease despite the nearly universal occurrence of retrograde menstruation could be explained by the presence of this allele," said Dr. Taylor, director of the division of reproductive endocrinology and infertility at Yale University, New Haven, Conn. The findings were published in the March issue of EMBO Molecular Medicine (EMBO Mol. Med. 2012;4:206-17) (Olga Grechukhina is the first author).

Since the mutation occurs only in a subgroup of women with endometriosis, genetic testing cannot be used as a screening tool. However, the recognition of KRAS-related endometriosis may allow for screening of family members and may have value for personalizing treatment of endometriosis, said Dr. Taylor.

Several lines of evidence reported by Dr. Taylor pinpoint the importance of this genetic mutation. In addition to the clinical observation that 31% of the sample of 132 women with endometriosis had this polymorphism compared with 5.8% of the control population, KRAS mRNA and protein levels were significantly increased in cultured endometrial stromal cells of women with the KRAS variant.

Dr. Taylor also looked at the behavior of endometrial stromal cells from women with and without the variant. Compared with cells from women without endometriosis, cells from women with endometriosis but without the variant were more invasive and proliferative. But cells from women with endometriosis and the variant had even higher levels of invasiveness and proliferation.

In another experiment, cells taken from women with endometriosis were transplanted under the kidney capsules of immunodeficient mice. Cells from the women with the mutation proliferated faster and had a lower expression of the progesterone receptor. "Progesterone resistance is characteristic of some women with endometriosis," commented Dr. Taylor.

Women with the mutation have a much lower expression of all let-7 miRNAs, not just let-7a. "Let-7 doesn’t just bind KRAS – it binds and generally downregulates many genes. When let-7 is inhibited, it no longer stops the expression of many genes involved in mitotic signaling, cell cycling and cell adhesion and migration," explained Dr. Taylor.

Dr. Taylor had no relevant financial disclosures.

NEW YORK – Almost one-third of 132 women with endometriosis had a genetic mutation affecting expression of the KRAS gene, compared with only 5.8% of the general population, according to Dr. Hugh S. Taylor, who presented the findings at the annual congress of the Endometriosis Foundation of America.

"This is the only clearly identified genetic cause of endometriosis," explained Dr. Taylor. The KRAS oncogene produces a protein involved primarily in regulating cell division. The defect found in the women with endometriosis has been localized to a regulatory region of the KRAS gene: the let-7 microRNA (miRNA) binding site in the 3’-untranslated region (UTR).

A high proliferation and invasion rate was seen in endometrial cells from women with the variant allele. These properties may facilitate the invasion of endometrial cells into peritoneum and ovarian cortex.

"This mechanism supports the most accepted theory for the origin of endometriosis – retrograde menstruation and subsequent implantation and invasion of susceptible tissues ... The fact that only a portion of women develop this disease despite the nearly universal occurrence of retrograde menstruation could be explained by the presence of this allele," said Dr. Taylor, director of the division of reproductive endocrinology and infertility at Yale University, New Haven, Conn. The findings were published in the March issue of EMBO Molecular Medicine (EMBO Mol. Med. 2012;4:206-17) (Olga Grechukhina is the first author).

Since the mutation occurs only in a subgroup of women with endometriosis, genetic testing cannot be used as a screening tool. However, the recognition of KRAS-related endometriosis may allow for screening of family members and may have value for personalizing treatment of endometriosis, said Dr. Taylor.

Several lines of evidence reported by Dr. Taylor pinpoint the importance of this genetic mutation. In addition to the clinical observation that 31% of the sample of 132 women with endometriosis had this polymorphism compared with 5.8% of the control population, KRAS mRNA and protein levels were significantly increased in cultured endometrial stromal cells of women with the KRAS variant.

Dr. Taylor also looked at the behavior of endometrial stromal cells from women with and without the variant. Compared with cells from women without endometriosis, cells from women with endometriosis but without the variant were more invasive and proliferative. But cells from women with endometriosis and the variant had even higher levels of invasiveness and proliferation.

In another experiment, cells taken from women with endometriosis were transplanted under the kidney capsules of immunodeficient mice. Cells from the women with the mutation proliferated faster and had a lower expression of the progesterone receptor. "Progesterone resistance is characteristic of some women with endometriosis," commented Dr. Taylor.

Women with the mutation have a much lower expression of all let-7 miRNAs, not just let-7a. "Let-7 doesn’t just bind KRAS – it binds and generally downregulates many genes. When let-7 is inhibited, it no longer stops the expression of many genes involved in mitotic signaling, cell cycling and cell adhesion and migration," explained Dr. Taylor.

Dr. Taylor had no relevant financial disclosures.

NEW YORK – Among new medications under development for rheumatoid arthritis, oral Janus kinase inhibitors appear to be close to coming to market and have strong supportive clinical data, according to Dr. Martin Jan Bergman at a course sponsored by New York University.

Unlike most drugs for RA that affect extracellular cytokines, oral JAK inhibitors are small molecules that act to disrupt one of the intracellular signal pathways used by some cytokines to regulate immune and regulatory responses. Of this family of drugs, Pfizer’s tofacitinib primarily targets JAK3 (the JAK protein kinase that is most associated with inflammation), although it also overlaps to JAK1 and JAK2.

On Dec. 20, Pfizer announced that the Food and Drug Administration has accepted a New Drug Application for tofacitinib, formerly known as tasocitinib. About 1 month earlier, the European Medicines Agency had taken similar action, according to Pfizer.

According to Pfizer, nearly 5,000 patients with RA have undergone treatment in clinical trials of tofacitinib held at more than 350 sites in 35 countries worldwide. The data come primarily from the ORAL (Oral Rheumatoid Arthritis Phase III) trials, comprising five studies for which the data necessary for registration are complete, and one ongoing phase III trial. Two long-term, open-label extension studies are also ongoing.

During his presentation, Dr. Bergman reviewed data presented in 2001 at the annual European Congress of Rheumatology by Dr. Joel M. Kremer, head of the division of rheumatology at Albany (N.Y.) Medical College. Those data concerned the effects of tofacitinib in patients whose active RA had not responded to therapy with DMARDs (disease-modifying antirheumatic drugs). Patients received tofacitinib in doses of either 5 mg or 10 mg, in combination with background DMARDs. In this double-blind, placebo-controlled, randomized study of 792 patients, any patient in the placebo group who had not met the target efficacy response by 3 months was switched to tofacitinib 5 mg or 10 mg. All remaining placebo-treated patients were switched to tofacitinib by 6 months. At 6 months, 52.7% in those treated with tofacitinib 5 mg achieved ACR 20 (defined as 20% improvement on an American College of Rheumatology evaluation scale), as did 58.3% in those treated at the 10-mg dose, a response significantly greater than the placebo group. "Now we are starting to see levels that we see with [tumor necrosis factor] inhibitors," said Dr. Bergman of Drexel University in Philadelphia.

Dr. Kremer also found significant improvement on the DAS28-4 (ESR) – that is, the Disease Activity Score including a 28-joint count and the erythrocyte sedimentation rate – less than 2.6 for both doses of tofacitinib, as well as on the HAQ-DI (Health Assessment Questionnaire–Disability Index). "The minimally clinically important (MCI) difference for the HAQ-DI is 0.21 or 0.23; patients on tofacitinib had double the MCI improvement," noted Dr. Bergman, referring to the change of –0.46 for the 5-mg dose and –0.56 for the 10-mg dose (P less than .001, compared with placebo, for both differences). "What we see is very reassuring."

Dr. Bergman then highlighted some of data included in nine abstracts presented on tofacitinib at the 2011 annual meeting of the American College of Rheumatology. Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center, Dallas, addressed the question of whether tofacitinib’s efficacy and safety hold up against the standard of care, such as a tumor necrosis factor (TNF) inhibitor (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 408). In this 12-month trial, 717 patients were randomized to tofacitinib (5 mg or 10 mg twice daily), adalimumab (40-mg subcutaneous injections every 2 weeks), or placebo. "This was not a head-to-head trial, but rather comparability vs. placebo," commented Dr. Bergman. The results showed that tofacitinib 5 mg and 10 mg, as well as adalimumab, were statistically superior to placebo for all primary efficacy end points, and efficacy results for tofacitinib and adalimumab were numerically similar. "The ACR 20 responses (tofacitinib 5 mg, 51.5%; tofacitinib 10 mg, 52.6%; adalimumab, 47.2%) are very robust and comparable to the responses we see [with anti-TNFs] all the time," he added.

Tofacitinib also holds promise as a rescue therapy for RA patients with inadequate response to TNF inhibitors, as suggested by the results of a study by Dr. Gerd-Rüdiger Burmester of Charité Medical University Berlin (Arthritis Rheum. 2011;63[suppl.]:S279; abstract 718). In this 6-month study of 399 patients who were randomized to 5 mg or 10 mg of tofacitinib or placebo (or who were first treated with placebo and then given tofacitinib), rapid, significant and clinically meaningful improvements were noted in the signs and symptoms of RA (according to ACR 20/50/70 scores), physical functioning (per HAQ-DI scores) and disease activity (per DAS28-4 [ESR] scores less than 2.6). After looking at the ACR responses of the group that was initially given placebo and then 5-mg tofacitinib, Dr. Bergman commented that the 6-month ACR 20/50/70 responses (45.5, 28.79, and 10.6, respectively) were "identical to what we see with all of the rescue therapies currently available."

Interim results of a 24-month study regarding the effect of tofacitinib on radiographic progression were reported by Dr. Désirée van der Heijde of the department of rheumatology at Leiden (the Netherlands) University Medical Center (Arthritis Rheum. 2011;63[suppl.]:S1017-8; abstract 2592). The study included 797 patients with active RA who had a history of inadequate response to methotrexate and were on a stable dose of methotrexate. After 6 months of treatment, the mean change in the mTSS (modified Total Sharp Score) for tofacitinib 10 mg twice daily was 0.06, which was significantly lower (P less than .05) than placebo (mTSS, 0.47), indicating reduced progression of structural damage. The difference was not statistically significant for the 5-mg tofacitinib dose, in which the mTSS was 0.12.

In reviewing Dr. van der Heijde’s findings, Dr. Bergman questioned whether even a mean change of mTSS of 0.47 – on a scale of 0-400 – was clinically meaningful. At 12 months, the proportion of patients with no radiographic progression or no new erosions was greater in both tofacitinib groups, compared with placebo. "I don’t think we should make too much of these results, but I think the findings are reassuring that this oral medication has effects similar to the anti-TNFs," commented Dr. Bergman.

According to Dr. Bergman, more safety data are available for tofacitinib than for any other RA drug currently on the market, given its stage of development, especially as measured by patient-years. Two abstracts at the ACR annual meeting reported on long-term safety data, one summarizing pooled data from five randomized, double-blind, phase III studies, and two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 409) and the other just from the same two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S152-3; abstract 407). The former was an analysis by Dr. Stanley B. Cohen, a rheumatologist at the University of Texas, Dallas. It included 3,030 RA patients from the phase III trials and 3,227 from the long-term extensions, resulting in approximately 2,000 and 3,000 patient-years of exposure to tofacitinib. In the phase III studies, there were 12 deaths, with a death rate of 0.40% with tofacitinib (5 deaths caused by infections, and 2 with cardiovascular causes), and 8 deaths in the long-term extensions (3 from infections, and 1 with a cardiovascular cause), with a death rate of 0.62%; the rate for placebo was 0.15%. This rate was comparable with that reported for adalimumab (0.49%).

The rates of serious infections were 2% in the tofacitinib phase III studies, and 2.9% in the tofacitinib long-term extensions, compared with 1.5% for adalimumab. There was some indication in the long-term extension data that the higher dose was associated with more serious infections than was the lower dose. Whether tofacitinib was given as monotherapy or with background DMARDs did not change the infection rate. Opportunistic infections, including tuberculosis, were uncommon.

In the second analysis, based on data from the long-term extension studies and reported by Dr. Jürgen Wollenhaupt of the University of Hamburg (Germany), there were some adverse events to "keep an eye out for," commented Dr. Bergman. This report represented data on 3,227 patients who were treated for a total duration of 3,118 patient-years. Serious adverse events were reported in 10.5% of patients. Confirmed increases in creatinine (defined as greater than 33% from baseline) were found in 12.2% of patients. Decreased hemoglobin levels (greater than or equal to 2 g/dL or less than 8) were found in 2.5% of patients, and raised aminotransferase levels (defined as greater than three times the upper limit of normal) were found in 1.7% (alanine) and 1.1% (aspartate) of patients. A 15% persistent rise across all doses was seen in total cholesterol. Diarrhea may also be a problem for some patients.

Dr. Bergman serves as a consultant to Pfizer.

NEW YORK – Among new medications under development for rheumatoid arthritis, oral Janus kinase inhibitors appear to be close to coming to market and have strong supportive clinical data, according to Dr. Martin Jan Bergman at a course sponsored by New York University.

Unlike most drugs for RA that affect extracellular cytokines, oral JAK inhibitors are small molecules that act to disrupt one of the intracellular signal pathways used by some cytokines to regulate immune and regulatory responses. Of this family of drugs, Pfizer’s tofacitinib primarily targets JAK3 (the JAK protein kinase that is most associated with inflammation), although it also overlaps to JAK1 and JAK2.

On Dec. 20, Pfizer announced that the Food and Drug Administration has accepted a New Drug Application for tofacitinib, formerly known as tasocitinib. About 1 month earlier, the European Medicines Agency had taken similar action, according to Pfizer.

According to Pfizer, nearly 5,000 patients with RA have undergone treatment in clinical trials of tofacitinib held at more than 350 sites in 35 countries worldwide. The data come primarily from the ORAL (Oral Rheumatoid Arthritis Phase III) trials, comprising five studies for which the data necessary for registration are complete, and one ongoing phase III trial. Two long-term, open-label extension studies are also ongoing.

During his presentation, Dr. Bergman reviewed data presented in 2001 at the annual European Congress of Rheumatology by Dr. Joel M. Kremer, head of the division of rheumatology at Albany (N.Y.) Medical College. Those data concerned the effects of tofacitinib in patients whose active RA had not responded to therapy with DMARDs (disease-modifying antirheumatic drugs). Patients received tofacitinib in doses of either 5 mg or 10 mg, in combination with background DMARDs. In this double-blind, placebo-controlled, randomized study of 792 patients, any patient in the placebo group who had not met the target efficacy response by 3 months was switched to tofacitinib 5 mg or 10 mg. All remaining placebo-treated patients were switched to tofacitinib by 6 months. At 6 months, 52.7% in those treated with tofacitinib 5 mg achieved ACR 20 (defined as 20% improvement on an American College of Rheumatology evaluation scale), as did 58.3% in those treated at the 10-mg dose, a response significantly greater than the placebo group. "Now we are starting to see levels that we see with [tumor necrosis factor] inhibitors," said Dr. Bergman of Drexel University in Philadelphia.

Dr. Kremer also found significant improvement on the DAS28-4 (ESR) – that is, the Disease Activity Score including a 28-joint count and the erythrocyte sedimentation rate – less than 2.6 for both doses of tofacitinib, as well as on the HAQ-DI (Health Assessment Questionnaire–Disability Index). "The minimally clinically important (MCI) difference for the HAQ-DI is 0.21 or 0.23; patients on tofacitinib had double the MCI improvement," noted Dr. Bergman, referring to the change of –0.46 for the 5-mg dose and –0.56 for the 10-mg dose (P less than .001, compared with placebo, for both differences). "What we see is very reassuring."

Dr. Bergman then highlighted some of data included in nine abstracts presented on tofacitinib at the 2011 annual meeting of the American College of Rheumatology. Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center, Dallas, addressed the question of whether tofacitinib’s efficacy and safety hold up against the standard of care, such as a tumor necrosis factor (TNF) inhibitor (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 408). In this 12-month trial, 717 patients were randomized to tofacitinib (5 mg or 10 mg twice daily), adalimumab (40-mg subcutaneous injections every 2 weeks), or placebo. "This was not a head-to-head trial, but rather comparability vs. placebo," commented Dr. Bergman. The results showed that tofacitinib 5 mg and 10 mg, as well as adalimumab, were statistically superior to placebo for all primary efficacy end points, and efficacy results for tofacitinib and adalimumab were numerically similar. "The ACR 20 responses (tofacitinib 5 mg, 51.5%; tofacitinib 10 mg, 52.6%; adalimumab, 47.2%) are very robust and comparable to the responses we see [with anti-TNFs] all the time," he added.

Tofacitinib also holds promise as a rescue therapy for RA patients with inadequate response to TNF inhibitors, as suggested by the results of a study by Dr. Gerd-Rüdiger Burmester of Charité Medical University Berlin (Arthritis Rheum. 2011;63[suppl.]:S279; abstract 718). In this 6-month study of 399 patients who were randomized to 5 mg or 10 mg of tofacitinib or placebo (or who were first treated with placebo and then given tofacitinib), rapid, significant and clinically meaningful improvements were noted in the signs and symptoms of RA (according to ACR 20/50/70 scores), physical functioning (per HAQ-DI scores) and disease activity (per DAS28-4 [ESR] scores less than 2.6). After looking at the ACR responses of the group that was initially given placebo and then 5-mg tofacitinib, Dr. Bergman commented that the 6-month ACR 20/50/70 responses (45.5, 28.79, and 10.6, respectively) were "identical to what we see with all of the rescue therapies currently available."

Interim results of a 24-month study regarding the effect of tofacitinib on radiographic progression were reported by Dr. Désirée van der Heijde of the department of rheumatology at Leiden (the Netherlands) University Medical Center (Arthritis Rheum. 2011;63[suppl.]:S1017-8; abstract 2592). The study included 797 patients with active RA who had a history of inadequate response to methotrexate and were on a stable dose of methotrexate. After 6 months of treatment, the mean change in the mTSS (modified Total Sharp Score) for tofacitinib 10 mg twice daily was 0.06, which was significantly lower (P less than .05) than placebo (mTSS, 0.47), indicating reduced progression of structural damage. The difference was not statistically significant for the 5-mg tofacitinib dose, in which the mTSS was 0.12.

In reviewing Dr. van der Heijde’s findings, Dr. Bergman questioned whether even a mean change of mTSS of 0.47 – on a scale of 0-400 – was clinically meaningful. At 12 months, the proportion of patients with no radiographic progression or no new erosions was greater in both tofacitinib groups, compared with placebo. "I don’t think we should make too much of these results, but I think the findings are reassuring that this oral medication has effects similar to the anti-TNFs," commented Dr. Bergman.

According to Dr. Bergman, more safety data are available for tofacitinib than for any other RA drug currently on the market, given its stage of development, especially as measured by patient-years. Two abstracts at the ACR annual meeting reported on long-term safety data, one summarizing pooled data from five randomized, double-blind, phase III studies, and two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 409) and the other just from the same two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S152-3; abstract 407). The former was an analysis by Dr. Stanley B. Cohen, a rheumatologist at the University of Texas, Dallas. It included 3,030 RA patients from the phase III trials and 3,227 from the long-term extensions, resulting in approximately 2,000 and 3,000 patient-years of exposure to tofacitinib. In the phase III studies, there were 12 deaths, with a death rate of 0.40% with tofacitinib (5 deaths caused by infections, and 2 with cardiovascular causes), and 8 deaths in the long-term extensions (3 from infections, and 1 with a cardiovascular cause), with a death rate of 0.62%; the rate for placebo was 0.15%. This rate was comparable with that reported for adalimumab (0.49%).

The rates of serious infections were 2% in the tofacitinib phase III studies, and 2.9% in the tofacitinib long-term extensions, compared with 1.5% for adalimumab. There was some indication in the long-term extension data that the higher dose was associated with more serious infections than was the lower dose. Whether tofacitinib was given as monotherapy or with background DMARDs did not change the infection rate. Opportunistic infections, including tuberculosis, were uncommon.

In the second analysis, based on data from the long-term extension studies and reported by Dr. Jürgen Wollenhaupt of the University of Hamburg (Germany), there were some adverse events to "keep an eye out for," commented Dr. Bergman. This report represented data on 3,227 patients who were treated for a total duration of 3,118 patient-years. Serious adverse events were reported in 10.5% of patients. Confirmed increases in creatinine (defined as greater than 33% from baseline) were found in 12.2% of patients. Decreased hemoglobin levels (greater than or equal to 2 g/dL or less than 8) were found in 2.5% of patients, and raised aminotransferase levels (defined as greater than three times the upper limit of normal) were found in 1.7% (alanine) and 1.1% (aspartate) of patients. A 15% persistent rise across all doses was seen in total cholesterol. Diarrhea may also be a problem for some patients.

Dr. Bergman serves as a consultant to Pfizer.

NEW YORK – Among new medications under development for rheumatoid arthritis, oral Janus kinase inhibitors appear to be close to coming to market and have strong supportive clinical data, according to Dr. Martin Jan Bergman at a course sponsored by New York University.

Unlike most drugs for RA that affect extracellular cytokines, oral JAK inhibitors are small molecules that act to disrupt one of the intracellular signal pathways used by some cytokines to regulate immune and regulatory responses. Of this family of drugs, Pfizer’s tofacitinib primarily targets JAK3 (the JAK protein kinase that is most associated with inflammation), although it also overlaps to JAK1 and JAK2.

On Dec. 20, Pfizer announced that the Food and Drug Administration has accepted a New Drug Application for tofacitinib, formerly known as tasocitinib. About 1 month earlier, the European Medicines Agency had taken similar action, according to Pfizer.

According to Pfizer, nearly 5,000 patients with RA have undergone treatment in clinical trials of tofacitinib held at more than 350 sites in 35 countries worldwide. The data come primarily from the ORAL (Oral Rheumatoid Arthritis Phase III) trials, comprising five studies for which the data necessary for registration are complete, and one ongoing phase III trial. Two long-term, open-label extension studies are also ongoing.

During his presentation, Dr. Bergman reviewed data presented in 2001 at the annual European Congress of Rheumatology by Dr. Joel M. Kremer, head of the division of rheumatology at Albany (N.Y.) Medical College. Those data concerned the effects of tofacitinib in patients whose active RA had not responded to therapy with DMARDs (disease-modifying antirheumatic drugs). Patients received tofacitinib in doses of either 5 mg or 10 mg, in combination with background DMARDs. In this double-blind, placebo-controlled, randomized study of 792 patients, any patient in the placebo group who had not met the target efficacy response by 3 months was switched to tofacitinib 5 mg or 10 mg. All remaining placebo-treated patients were switched to tofacitinib by 6 months. At 6 months, 52.7% in those treated with tofacitinib 5 mg achieved ACR 20 (defined as 20% improvement on an American College of Rheumatology evaluation scale), as did 58.3% in those treated at the 10-mg dose, a response significantly greater than the placebo group. "Now we are starting to see levels that we see with [tumor necrosis factor] inhibitors," said Dr. Bergman of Drexel University in Philadelphia.

Dr. Kremer also found significant improvement on the DAS28-4 (ESR) – that is, the Disease Activity Score including a 28-joint count and the erythrocyte sedimentation rate – less than 2.6 for both doses of tofacitinib, as well as on the HAQ-DI (Health Assessment Questionnaire–Disability Index). "The minimally clinically important (MCI) difference for the HAQ-DI is 0.21 or 0.23; patients on tofacitinib had double the MCI improvement," noted Dr. Bergman, referring to the change of –0.46 for the 5-mg dose and –0.56 for the 10-mg dose (P less than .001, compared with placebo, for both differences). "What we see is very reassuring."

Dr. Bergman then highlighted some of data included in nine abstracts presented on tofacitinib at the 2011 annual meeting of the American College of Rheumatology. Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center, Dallas, addressed the question of whether tofacitinib’s efficacy and safety hold up against the standard of care, such as a tumor necrosis factor (TNF) inhibitor (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 408). In this 12-month trial, 717 patients were randomized to tofacitinib (5 mg or 10 mg twice daily), adalimumab (40-mg subcutaneous injections every 2 weeks), or placebo. "This was not a head-to-head trial, but rather comparability vs. placebo," commented Dr. Bergman. The results showed that tofacitinib 5 mg and 10 mg, as well as adalimumab, were statistically superior to placebo for all primary efficacy end points, and efficacy results for tofacitinib and adalimumab were numerically similar. "The ACR 20 responses (tofacitinib 5 mg, 51.5%; tofacitinib 10 mg, 52.6%; adalimumab, 47.2%) are very robust and comparable to the responses we see [with anti-TNFs] all the time," he added.

Tofacitinib also holds promise as a rescue therapy for RA patients with inadequate response to TNF inhibitors, as suggested by the results of a study by Dr. Gerd-Rüdiger Burmester of Charité Medical University Berlin (Arthritis Rheum. 2011;63[suppl.]:S279; abstract 718). In this 6-month study of 399 patients who were randomized to 5 mg or 10 mg of tofacitinib or placebo (or who were first treated with placebo and then given tofacitinib), rapid, significant and clinically meaningful improvements were noted in the signs and symptoms of RA (according to ACR 20/50/70 scores), physical functioning (per HAQ-DI scores) and disease activity (per DAS28-4 [ESR] scores less than 2.6). After looking at the ACR responses of the group that was initially given placebo and then 5-mg tofacitinib, Dr. Bergman commented that the 6-month ACR 20/50/70 responses (45.5, 28.79, and 10.6, respectively) were "identical to what we see with all of the rescue therapies currently available."

Interim results of a 24-month study regarding the effect of tofacitinib on radiographic progression were reported by Dr. Désirée van der Heijde of the department of rheumatology at Leiden (the Netherlands) University Medical Center (Arthritis Rheum. 2011;63[suppl.]:S1017-8; abstract 2592). The study included 797 patients with active RA who had a history of inadequate response to methotrexate and were on a stable dose of methotrexate. After 6 months of treatment, the mean change in the mTSS (modified Total Sharp Score) for tofacitinib 10 mg twice daily was 0.06, which was significantly lower (P less than .05) than placebo (mTSS, 0.47), indicating reduced progression of structural damage. The difference was not statistically significant for the 5-mg tofacitinib dose, in which the mTSS was 0.12.

In reviewing Dr. van der Heijde’s findings, Dr. Bergman questioned whether even a mean change of mTSS of 0.47 – on a scale of 0-400 – was clinically meaningful. At 12 months, the proportion of patients with no radiographic progression or no new erosions was greater in both tofacitinib groups, compared with placebo. "I don’t think we should make too much of these results, but I think the findings are reassuring that this oral medication has effects similar to the anti-TNFs," commented Dr. Bergman.

According to Dr. Bergman, more safety data are available for tofacitinib than for any other RA drug currently on the market, given its stage of development, especially as measured by patient-years. Two abstracts at the ACR annual meeting reported on long-term safety data, one summarizing pooled data from five randomized, double-blind, phase III studies, and two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 409) and the other just from the same two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S152-3; abstract 407). The former was an analysis by Dr. Stanley B. Cohen, a rheumatologist at the University of Texas, Dallas. It included 3,030 RA patients from the phase III trials and 3,227 from the long-term extensions, resulting in approximately 2,000 and 3,000 patient-years of exposure to tofacitinib. In the phase III studies, there were 12 deaths, with a death rate of 0.40% with tofacitinib (5 deaths caused by infections, and 2 with cardiovascular causes), and 8 deaths in the long-term extensions (3 from infections, and 1 with a cardiovascular cause), with a death rate of 0.62%; the rate for placebo was 0.15%. This rate was comparable with that reported for adalimumab (0.49%).

The rates of serious infections were 2% in the tofacitinib phase III studies, and 2.9% in the tofacitinib long-term extensions, compared with 1.5% for adalimumab. There was some indication in the long-term extension data that the higher dose was associated with more serious infections than was the lower dose. Whether tofacitinib was given as monotherapy or with background DMARDs did not change the infection rate. Opportunistic infections, including tuberculosis, were uncommon.

In the second analysis, based on data from the long-term extension studies and reported by Dr. Jürgen Wollenhaupt of the University of Hamburg (Germany), there were some adverse events to "keep an eye out for," commented Dr. Bergman. This report represented data on 3,227 patients who were treated for a total duration of 3,118 patient-years. Serious adverse events were reported in 10.5% of patients. Confirmed increases in creatinine (defined as greater than 33% from baseline) were found in 12.2% of patients. Decreased hemoglobin levels (greater than or equal to 2 g/dL or less than 8) were found in 2.5% of patients, and raised aminotransferase levels (defined as greater than three times the upper limit of normal) were found in 1.7% (alanine) and 1.1% (aspartate) of patients. A 15% persistent rise across all doses was seen in total cholesterol. Diarrhea may also be a problem for some patients.

Dr. Bergman serves as a consultant to Pfizer.

NEW YORK – Tocilizumab monotherapy is a viable alternative treatment for patients with moderate to severe rheumatoid arthritis who have not responded to methotrexate in use with the biologic, according to Dr. Yusuf Yazici, speaking at a meeting sponsored by New York University.

"One paradigm of RA treatment is that a biologic alone is equivalent to methotrexate alone, but that the combination is better. These data suggest that tocilizumab may possibly be used alone," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the NYU Hospital for Joint Diseases.

Data from the ACT-RAY trial, which was presented by Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Cochin Hospital, Paris, at the 2011 annual meeting of the American College of Rheumatology, showed that the DAS28 remission rate was 35% for tocilizumab plus placebo, compared with 40% for tocilizumab plus methotrexate, a difference that was not statistically significant (P = .19; 95% confidence interval, 2.4%-13.7%).

There were also no significant differences among ACR 20/50/70/90 response rates between groups. For both groups, the onset of action was comparable, with 18.1% of the combination group and 15.2% of the tocilizumab monotherapy group achieving remission by week 8.

The ACT-RAY trial is a phase IIIb double-blind 2-year study of biologic-naive adults with moderate to severe active RA who were considered to be inadequate responders to methotrexate. Of the 556 patients enrolled, 279 were randomized to tocilizumab (8 mg/kg every 4 weeks) plus a stable dose of methotrexate and 277 received the same dose of tocilizumab plus placebo for 24 weeks. Radiographs taken of the hands and feet at baseline and 24 weeks were assessed for structural changes.

Secondary outcomes, such as progression of structural damage as measured by the Genant-modified Sharp score (GSS) and joint space narrowing score, also showed no significant differences between treatment groups. On several measures, including total GSS scores, the proportion of patients with no progression of structural damage was similar (for example, 65.3% for the combination treatment vs. 58.7% for tocilizumab monotherapy). Improvements from baseline on the Health-Assessment Questionnaire Disability Index and rheumatoid arthritis quality of life score were comparable.

As far as safety, rates of adverse events, serious adverse events, and serious infections per 100 patient-years were indistinguishable.

"There are other pieces of information pointing in the same direction, where for most of the outcome measures there was no difference between the groups; however, some favored the combination arm. None of the studies by themselves prove that monotherapy is as good as combination treatment, but the data provide information that tocilizumab monotherapy is a good option for some patients," said Dr Yazici.

"It would be good to do a study that looks at truly methotrexate-naive patients with early disease and see how tocilizumab monotherapy compares to methotrexate alone and a combination of tocilizumab with methotrexate.

"While the AMBITION study (Ann. Rheum. Dis. 2010;69:88-96) reported that tocilizumab monotherapy was better than methotrexate alone, one-third of patients had been on methotrexate before the trial but discontinued treatment. Those patients are not going to have as robust a response with methotrexate as those who are truly methotrexate naive."

Dr. Yazici also spoke about the results of the ACT-STAR study, a prospective, 24-week open label trial, which were presented at the 2011 annual meeting of the American College of Rheumatology by Dr. Michael E. Weinblatt, codirector of clinical rheumatology at the Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

In this trial, the enrolled patients were inadequate responders to anti-tumor necrosis factor (anti-TNF) therapy. No significant differences were found on the ACR 20/50/70 among those treated with tocilizumab monotherapy (8 mg/kg, n = 129) and those who received a combination of tocilizumab plus a DMARD (those in the combination group received either tocilizumab 8 mg/kg throughout the trial (n = 221) while others began with a 4 mg/kg dose which then was raised to 8 mg/kg (n = 322)).

While the study concluded that tocilizumab monotherapy was similar to combination therapy, Dr. Yazici commented that the randomization process used was inadequate as this was an open label trial and the data needs to be interpreted with this in mind. He said, "However, all these studies suggest that there may be a role for tocilizumab monotherapy in patients who have had an inadequate response to methotrexate in the past."

Tocilizumab, a biologic that targets interleukin-6 receptors, was approved in the United States in January 2010 for the treatment of adults with moderate to severe, active RA who have had an inadequate response to one or more TNF inhibitors. Tocilizumab monotherapy could be particularly beneficial for those with RA who respond poorly to methotrexate or experience adverse effects from it.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech.

NEW YORK – Tocilizumab monotherapy is a viable alternative treatment for patients with moderate to severe rheumatoid arthritis who have not responded to methotrexate in use with the biologic, according to Dr. Yusuf Yazici, speaking at a meeting sponsored by New York University.

"One paradigm of RA treatment is that a biologic alone is equivalent to methotrexate alone, but that the combination is better. These data suggest that tocilizumab may possibly be used alone," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the NYU Hospital for Joint Diseases.

Data from the ACT-RAY trial, which was presented by Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Cochin Hospital, Paris, at the 2011 annual meeting of the American College of Rheumatology, showed that the DAS28 remission rate was 35% for tocilizumab plus placebo, compared with 40% for tocilizumab plus methotrexate, a difference that was not statistically significant (P = .19; 95% confidence interval, 2.4%-13.7%).

There were also no significant differences among ACR 20/50/70/90 response rates between groups. For both groups, the onset of action was comparable, with 18.1% of the combination group and 15.2% of the tocilizumab monotherapy group achieving remission by week 8.

The ACT-RAY trial is a phase IIIb double-blind 2-year study of biologic-naive adults with moderate to severe active RA who were considered to be inadequate responders to methotrexate. Of the 556 patients enrolled, 279 were randomized to tocilizumab (8 mg/kg every 4 weeks) plus a stable dose of methotrexate and 277 received the same dose of tocilizumab plus placebo for 24 weeks. Radiographs taken of the hands and feet at baseline and 24 weeks were assessed for structural changes.

Secondary outcomes, such as progression of structural damage as measured by the Genant-modified Sharp score (GSS) and joint space narrowing score, also showed no significant differences between treatment groups. On several measures, including total GSS scores, the proportion of patients with no progression of structural damage was similar (for example, 65.3% for the combination treatment vs. 58.7% for tocilizumab monotherapy). Improvements from baseline on the Health-Assessment Questionnaire Disability Index and rheumatoid arthritis quality of life score were comparable.

As far as safety, rates of adverse events, serious adverse events, and serious infections per 100 patient-years were indistinguishable.

"There are other pieces of information pointing in the same direction, where for most of the outcome measures there was no difference between the groups; however, some favored the combination arm. None of the studies by themselves prove that monotherapy is as good as combination treatment, but the data provide information that tocilizumab monotherapy is a good option for some patients," said Dr Yazici.

"It would be good to do a study that looks at truly methotrexate-naive patients with early disease and see how tocilizumab monotherapy compares to methotrexate alone and a combination of tocilizumab with methotrexate.

"While the AMBITION study (Ann. Rheum. Dis. 2010;69:88-96) reported that tocilizumab monotherapy was better than methotrexate alone, one-third of patients had been on methotrexate before the trial but discontinued treatment. Those patients are not going to have as robust a response with methotrexate as those who are truly methotrexate naive."

Dr. Yazici also spoke about the results of the ACT-STAR study, a prospective, 24-week open label trial, which were presented at the 2011 annual meeting of the American College of Rheumatology by Dr. Michael E. Weinblatt, codirector of clinical rheumatology at the Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

In this trial, the enrolled patients were inadequate responders to anti-tumor necrosis factor (anti-TNF) therapy. No significant differences were found on the ACR 20/50/70 among those treated with tocilizumab monotherapy (8 mg/kg, n = 129) and those who received a combination of tocilizumab plus a DMARD (those in the combination group received either tocilizumab 8 mg/kg throughout the trial (n = 221) while others began with a 4 mg/kg dose which then was raised to 8 mg/kg (n = 322)).

While the study concluded that tocilizumab monotherapy was similar to combination therapy, Dr. Yazici commented that the randomization process used was inadequate as this was an open label trial and the data needs to be interpreted with this in mind. He said, "However, all these studies suggest that there may be a role for tocilizumab monotherapy in patients who have had an inadequate response to methotrexate in the past."

Tocilizumab, a biologic that targets interleukin-6 receptors, was approved in the United States in January 2010 for the treatment of adults with moderate to severe, active RA who have had an inadequate response to one or more TNF inhibitors. Tocilizumab monotherapy could be particularly beneficial for those with RA who respond poorly to methotrexate or experience adverse effects from it.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech.

NEW YORK – Tocilizumab monotherapy is a viable alternative treatment for patients with moderate to severe rheumatoid arthritis who have not responded to methotrexate in use with the biologic, according to Dr. Yusuf Yazici, speaking at a meeting sponsored by New York University.

"One paradigm of RA treatment is that a biologic alone is equivalent to methotrexate alone, but that the combination is better. These data suggest that tocilizumab may possibly be used alone," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the NYU Hospital for Joint Diseases.

Data from the ACT-RAY trial, which was presented by Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Cochin Hospital, Paris, at the 2011 annual meeting of the American College of Rheumatology, showed that the DAS28 remission rate was 35% for tocilizumab plus placebo, compared with 40% for tocilizumab plus methotrexate, a difference that was not statistically significant (P = .19; 95% confidence interval, 2.4%-13.7%).

There were also no significant differences among ACR 20/50/70/90 response rates between groups. For both groups, the onset of action was comparable, with 18.1% of the combination group and 15.2% of the tocilizumab monotherapy group achieving remission by week 8.

The ACT-RAY trial is a phase IIIb double-blind 2-year study of biologic-naive adults with moderate to severe active RA who were considered to be inadequate responders to methotrexate. Of the 556 patients enrolled, 279 were randomized to tocilizumab (8 mg/kg every 4 weeks) plus a stable dose of methotrexate and 277 received the same dose of tocilizumab plus placebo for 24 weeks. Radiographs taken of the hands and feet at baseline and 24 weeks were assessed for structural changes.

Secondary outcomes, such as progression of structural damage as measured by the Genant-modified Sharp score (GSS) and joint space narrowing score, also showed no significant differences between treatment groups. On several measures, including total GSS scores, the proportion of patients with no progression of structural damage was similar (for example, 65.3% for the combination treatment vs. 58.7% for tocilizumab monotherapy). Improvements from baseline on the Health-Assessment Questionnaire Disability Index and rheumatoid arthritis quality of life score were comparable.

As far as safety, rates of adverse events, serious adverse events, and serious infections per 100 patient-years were indistinguishable.

"There are other pieces of information pointing in the same direction, where for most of the outcome measures there was no difference between the groups; however, some favored the combination arm. None of the studies by themselves prove that monotherapy is as good as combination treatment, but the data provide information that tocilizumab monotherapy is a good option for some patients," said Dr Yazici.

"It would be good to do a study that looks at truly methotrexate-naive patients with early disease and see how tocilizumab monotherapy compares to methotrexate alone and a combination of tocilizumab with methotrexate.

"While the AMBITION study (Ann. Rheum. Dis. 2010;69:88-96) reported that tocilizumab monotherapy was better than methotrexate alone, one-third of patients had been on methotrexate before the trial but discontinued treatment. Those patients are not going to have as robust a response with methotrexate as those who are truly methotrexate naive."

Dr. Yazici also spoke about the results of the ACT-STAR study, a prospective, 24-week open label trial, which were presented at the 2011 annual meeting of the American College of Rheumatology by Dr. Michael E. Weinblatt, codirector of clinical rheumatology at the Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

In this trial, the enrolled patients were inadequate responders to anti-tumor necrosis factor (anti-TNF) therapy. No significant differences were found on the ACR 20/50/70 among those treated with tocilizumab monotherapy (8 mg/kg, n = 129) and those who received a combination of tocilizumab plus a DMARD (those in the combination group received either tocilizumab 8 mg/kg throughout the trial (n = 221) while others began with a 4 mg/kg dose which then was raised to 8 mg/kg (n = 322)).

While the study concluded that tocilizumab monotherapy was similar to combination therapy, Dr. Yazici commented that the randomization process used was inadequate as this was an open label trial and the data needs to be interpreted with this in mind. He said, "However, all these studies suggest that there may be a role for tocilizumab monotherapy in patients who have had an inadequate response to methotrexate in the past."

Tocilizumab, a biologic that targets interleukin-6 receptors, was approved in the United States in January 2010 for the treatment of adults with moderate to severe, active RA who have had an inadequate response to one or more TNF inhibitors. Tocilizumab monotherapy could be particularly beneficial for those with RA who respond poorly to methotrexate or experience adverse effects from it.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech.

NEW YORK – Recent data indicate that the subcutaneous formulation of abatacept is comparable in safety to the intravenous formulation in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici, who spoke at "The ‘Tightrope’ of RA Therapy" course sponsored by New York University.

"For the first time, we have a biologic that is available in both infusible and injectable versions, giving patients an option of using one or the other," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics at New York University.

The subcutaneous formulation of abatacept became commercially available in September 2011.

Safety data were presented as part of the phase IIIb, double-blind, 6-month ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) registration trial of subcutaneous abatacept. That study, however, included fewer than 700 patients with rheumatoid arthritis (RA) in both the subcutaneous and intravenous arms (Arthritis Rheum. 2011;63:2854-64). Injection site reactions, including hematoma, pruritus, and erythema, were found in 2.6% of the subcutaneous group and 2.5% of the intravenous group. Serious infections were reported in 0.7% of the subcutaneous group and 1.4% of the intravenous group, said Dr. Yazici, who also is with the Behcet’s Syndrome Evaluation, Treatment, and Research Center at New York University.

A study presented at the 2011 EULAR (European League Against Rheumatism) annual congress by Dr. Rieke Alten, of the University of Medicine in Berlin, provided data on the long-term safety of subcutaneous abatacept. The study included pooled safety data from five clinical trials on 1,879 RA patients who had up to 4.5 years of exposure, representing 3,086 patient-years of use. The subcutaneous formulation was found to produce effects generally consistent with those of the intravenous formulation. Mean duration of exposure was 20 months in the subcutaneous group, compared with 36 months for the intravenous group. Data on the safety of the intravenous formulation came from an integrated safety analysis from the abatacept RA clinical trial program, which included 4,149 patients with 12,132 patient-years of exposure. These data were presented at the 2010 annual meeting of the American College of Rheumatology.

Dr. Alten found the incidence rate for death to be 0.55 events/100 patient-years in the subcutaneous group, compared with 0.60 in the intravenous group. The incidence rate for serious adverse events was 9.53 in the subcutaneous group vs. 14.61 in the intravenous group, and did not increase with increasing abatacept exposure over time. The incidence of injection site reactions in the subcutaneous group was 2.22, and more than 95% of reactions were mild.

As far as serious infections, the incidence rates of the most common ones after subcutaneous injections were 0.36 for pneumonia (vs. 0.46 in the intravenous group), 0.10 for lobar pneumonia (vs. 0.11), 0.10 for herpes zoster (vs. 0.03), and 0.03 (vs. 0.03) for tuberculosis. The incidence rates for malignancies, excluding nonmelanoma skin cancer, were 0.68 in patients receiving subcutaneous abatacept and 0.73 in the intravenous group. The incidence rates for autoimmune events, including psoriasis and Sjögren’s syndrome, were 1.28 with subcutaneous administration and 1.99 with intravenous use.

Unlike the intravenous formulation, subcutaneous abatacept can be self-administered, allowing patients to forego trips to the physician’s office for infusions – a benefit for those who have busy schedules or transportation limitations. Diabetics may prefer the subcutaneous formulation because it does not contain maltose, which can interfere with the accuracy of blood sugar readings. On the other hand, some patients may be anxious about self-injection or unwilling to take the time to secure their own supplies (such as bandages, alcohol swabs, cotton balls, and puncture-resistant containers for syringes) or prepare the syringes, which must be kept cool before use and then warmed before injection; they may prefer the monthly infusions given at the doctor’s office.

The label’s product information for abatacept recommends a single intravenous infusion as a loading dose (based on body weight) preceding the first 125-mg subcutaneous injection. Dr. Yazici reviewed recent data that challenged that recommendation. These findings come from a study by Dr. Peter T. Nash of the University of Queensland, Brisbane, that were presented at the 2011 EULAR congress. The study involved a comparison of open-label data from two phase III trials that showed comparable improvements with subcutaneous abatacept, with or without an intravenous loading dose, on physical function, as assessed by the Health Assessment Questionnaire–Disease Index, and disease activity, as assessed by the Disease Activity Score 28/C-reactive protein.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Alten receives grant or research support from, is a consultant for, or is on the speakers bureau of Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Norvartis Pharmaceuticals, Roche, and Wyeth Pharmaceuticals.

NEW YORK – Recent data indicate that the subcutaneous formulation of abatacept is comparable in safety to the intravenous formulation in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici, who spoke at "The ‘Tightrope’ of RA Therapy" course sponsored by New York University.

"For the first time, we have a biologic that is available in both infusible and injectable versions, giving patients an option of using one or the other," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics at New York University.

The subcutaneous formulation of abatacept became commercially available in September 2011.

Safety data were presented as part of the phase IIIb, double-blind, 6-month ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) registration trial of subcutaneous abatacept. That study, however, included fewer than 700 patients with rheumatoid arthritis (RA) in both the subcutaneous and intravenous arms (Arthritis Rheum. 2011;63:2854-64). Injection site reactions, including hematoma, pruritus, and erythema, were found in 2.6% of the subcutaneous group and 2.5% of the intravenous group. Serious infections were reported in 0.7% of the subcutaneous group and 1.4% of the intravenous group, said Dr. Yazici, who also is with the Behcet’s Syndrome Evaluation, Treatment, and Research Center at New York University.

A study presented at the 2011 EULAR (European League Against Rheumatism) annual congress by Dr. Rieke Alten, of the University of Medicine in Berlin, provided data on the long-term safety of subcutaneous abatacept. The study included pooled safety data from five clinical trials on 1,879 RA patients who had up to 4.5 years of exposure, representing 3,086 patient-years of use. The subcutaneous formulation was found to produce effects generally consistent with those of the intravenous formulation. Mean duration of exposure was 20 months in the subcutaneous group, compared with 36 months for the intravenous group. Data on the safety of the intravenous formulation came from an integrated safety analysis from the abatacept RA clinical trial program, which included 4,149 patients with 12,132 patient-years of exposure. These data were presented at the 2010 annual meeting of the American College of Rheumatology.

Dr. Alten found the incidence rate for death to be 0.55 events/100 patient-years in the subcutaneous group, compared with 0.60 in the intravenous group. The incidence rate for serious adverse events was 9.53 in the subcutaneous group vs. 14.61 in the intravenous group, and did not increase with increasing abatacept exposure over time. The incidence of injection site reactions in the subcutaneous group was 2.22, and more than 95% of reactions were mild.

As far as serious infections, the incidence rates of the most common ones after subcutaneous injections were 0.36 for pneumonia (vs. 0.46 in the intravenous group), 0.10 for lobar pneumonia (vs. 0.11), 0.10 for herpes zoster (vs. 0.03), and 0.03 (vs. 0.03) for tuberculosis. The incidence rates for malignancies, excluding nonmelanoma skin cancer, were 0.68 in patients receiving subcutaneous abatacept and 0.73 in the intravenous group. The incidence rates for autoimmune events, including psoriasis and Sjögren’s syndrome, were 1.28 with subcutaneous administration and 1.99 with intravenous use.

Unlike the intravenous formulation, subcutaneous abatacept can be self-administered, allowing patients to forego trips to the physician’s office for infusions – a benefit for those who have busy schedules or transportation limitations. Diabetics may prefer the subcutaneous formulation because it does not contain maltose, which can interfere with the accuracy of blood sugar readings. On the other hand, some patients may be anxious about self-injection or unwilling to take the time to secure their own supplies (such as bandages, alcohol swabs, cotton balls, and puncture-resistant containers for syringes) or prepare the syringes, which must be kept cool before use and then warmed before injection; they may prefer the monthly infusions given at the doctor’s office.

The label’s product information for abatacept recommends a single intravenous infusion as a loading dose (based on body weight) preceding the first 125-mg subcutaneous injection. Dr. Yazici reviewed recent data that challenged that recommendation. These findings come from a study by Dr. Peter T. Nash of the University of Queensland, Brisbane, that were presented at the 2011 EULAR congress. The study involved a comparison of open-label data from two phase III trials that showed comparable improvements with subcutaneous abatacept, with or without an intravenous loading dose, on physical function, as assessed by the Health Assessment Questionnaire–Disease Index, and disease activity, as assessed by the Disease Activity Score 28/C-reactive protein.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Alten receives grant or research support from, is a consultant for, or is on the speakers bureau of Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Norvartis Pharmaceuticals, Roche, and Wyeth Pharmaceuticals.

NEW YORK – Recent data indicate that the subcutaneous formulation of abatacept is comparable in safety to the intravenous formulation in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici, who spoke at "The ‘Tightrope’ of RA Therapy" course sponsored by New York University.

"For the first time, we have a biologic that is available in both infusible and injectable versions, giving patients an option of using one or the other," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics at New York University.

The subcutaneous formulation of abatacept became commercially available in September 2011.

Safety data were presented as part of the phase IIIb, double-blind, 6-month ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) registration trial of subcutaneous abatacept. That study, however, included fewer than 700 patients with rheumatoid arthritis (RA) in both the subcutaneous and intravenous arms (Arthritis Rheum. 2011;63:2854-64). Injection site reactions, including hematoma, pruritus, and erythema, were found in 2.6% of the subcutaneous group and 2.5% of the intravenous group. Serious infections were reported in 0.7% of the subcutaneous group and 1.4% of the intravenous group, said Dr. Yazici, who also is with the Behcet’s Syndrome Evaluation, Treatment, and Research Center at New York University.

A study presented at the 2011 EULAR (European League Against Rheumatism) annual congress by Dr. Rieke Alten, of the University of Medicine in Berlin, provided data on the long-term safety of subcutaneous abatacept. The study included pooled safety data from five clinical trials on 1,879 RA patients who had up to 4.5 years of exposure, representing 3,086 patient-years of use. The subcutaneous formulation was found to produce effects generally consistent with those of the intravenous formulation. Mean duration of exposure was 20 months in the subcutaneous group, compared with 36 months for the intravenous group. Data on the safety of the intravenous formulation came from an integrated safety analysis from the abatacept RA clinical trial program, which included 4,149 patients with 12,132 patient-years of exposure. These data were presented at the 2010 annual meeting of the American College of Rheumatology.

Dr. Alten found the incidence rate for death to be 0.55 events/100 patient-years in the subcutaneous group, compared with 0.60 in the intravenous group. The incidence rate for serious adverse events was 9.53 in the subcutaneous group vs. 14.61 in the intravenous group, and did not increase with increasing abatacept exposure over time. The incidence of injection site reactions in the subcutaneous group was 2.22, and more than 95% of reactions were mild.

As far as serious infections, the incidence rates of the most common ones after subcutaneous injections were 0.36 for pneumonia (vs. 0.46 in the intravenous group), 0.10 for lobar pneumonia (vs. 0.11), 0.10 for herpes zoster (vs. 0.03), and 0.03 (vs. 0.03) for tuberculosis. The incidence rates for malignancies, excluding nonmelanoma skin cancer, were 0.68 in patients receiving subcutaneous abatacept and 0.73 in the intravenous group. The incidence rates for autoimmune events, including psoriasis and Sjögren’s syndrome, were 1.28 with subcutaneous administration and 1.99 with intravenous use.

Unlike the intravenous formulation, subcutaneous abatacept can be self-administered, allowing patients to forego trips to the physician’s office for infusions – a benefit for those who have busy schedules or transportation limitations. Diabetics may prefer the subcutaneous formulation because it does not contain maltose, which can interfere with the accuracy of blood sugar readings. On the other hand, some patients may be anxious about self-injection or unwilling to take the time to secure their own supplies (such as bandages, alcohol swabs, cotton balls, and puncture-resistant containers for syringes) or prepare the syringes, which must be kept cool before use and then warmed before injection; they may prefer the monthly infusions given at the doctor’s office.

The label’s product information for abatacept recommends a single intravenous infusion as a loading dose (based on body weight) preceding the first 125-mg subcutaneous injection. Dr. Yazici reviewed recent data that challenged that recommendation. These findings come from a study by Dr. Peter T. Nash of the University of Queensland, Brisbane, that were presented at the 2011 EULAR congress. The study involved a comparison of open-label data from two phase III trials that showed comparable improvements with subcutaneous abatacept, with or without an intravenous loading dose, on physical function, as assessed by the Health Assessment Questionnaire–Disease Index, and disease activity, as assessed by the Disease Activity Score 28/C-reactive protein.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Alten receives grant or research support from, is a consultant for, or is on the speakers bureau of Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Norvartis Pharmaceuticals, Roche, and Wyeth Pharmaceuticals.

NEW YORK – The low levels of immunoglobulin G seen in a group of patients receiving rituximab for rheumatoid arthritis were associated with a twofold increased risk of serious infections, judging from the results of a 5-year prospective French register of 2,000 patients, according to Dr. Yusuf Yazici.

“These results give us one piece of evidence to support what investigators have long suspected: Low IgG levels may increase risk of infections,” said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the New York University Hospital for Joint Diseases.*

Of the risk factors investigated by Dr. Jacques-Eric Gottenberg of the Strasbourg (France) University Hospital and his associates, only low serum IgG levels – not gamma globulin or immunoglobulin M (IgM) levels – were associated with serious infections in rheumatoid arthritis (RA) patients treated with rituximab, according to Dr. Yazici. This finding suggests that serum IgG levels in particular should be checked before each new cycle of rituximab and that the risk/benefit ratio of rituximab should be carefully assessed for those with low IgG levels. A therapy other than rituximab should be considered for patients with low immunoglobulin G (IgG) levels who already have a severe infection or severe comorbidities, according to Dr. Gottenberg’s findings.

The French AIR (Autoimmunity and Rituximab) Registry is a 5-year, prospective, multicenter study begun in 2006 that prospectively collects data on patients treated with rituximab on and off label for refractory arthritides. It is thought to be the largest prospective study, based on a national registry, focusing on severe infections in RA patients treated with rituximab in a clinical setting. Many patients have comorbidities, such as cancer, chronic lung disease, cardiac insufficiency, or diabetes. A nationwide initiative, most patients were registered from rheumatology departments while less than 10% originated from internal medicine departments. The 88 centers who participated in the register write more than 85% of all rituximab prescriptions in France for nonhematologic, nononcologic indications.

"You can’t suppress IgG levels forever without expecting some increase in infections."

Since this was a noninterventional study, no laboratory exams were required either at baseline or after rituximab treatment. Even though immunoglobulin levels are not routinely assessed during rituximab therapy, of the 2000 patients with RA included in the AIR Registry, gamma globulin, IgM, or IgG levels after rituximab treatment had been collected in almost 60% of enrolled patients. Of those who had undergone these analyses, 15.5% had low levels of serum gamma globulin less than 6 g/L), 26.6% had low levels of IgM less than 0.5 g/L) and 12.1% had low IgG levels (less than 6 g/L).

The authors looked at the rates of serious infections (defined as an infection occurring during the 12 months following each infusion of rituximab that required hospitalization and/or intravenous antibiotics and/or resulted in death) in patients with normal and low levels of gamma globulin, IgM, or IgG. Univariate analysis adjusted according to follow-up duration revealed that only low IgG levels after rituximab were associated with a significantly increased risk of serious infections, with almost a twofold increase in risk (odds ratio, 1.99; 95% confidence interval, 1.2-3.3; P = .008). No significant effects were found for low levels of gamma globulin (OR, 1.5; 95% CI, 0.9-2.5; P = .09) or IgM (OR, 1.5; 95% CI, 0.9-2.3; P = .08).

In a multivariate analysis, when the researchers adjusted for older age, previous cancer, or serious or recurrent infections, only low IgG after rituximab remained associated with serious infections. In published work, Dr. Gottenberg reported that chronic lung disease and/or cardiac insufficiency and extraarticular involvement also rendered RA patients treated with rituximab more prone to severe infections (Arthritis Rheum. 2010;62[9]:2625-32).

For all measures serious infections were more frequent in those with lower levels of immunologic indices. For instance, 13.5% of patients with low gamma globulin levels after rituximab had serious infections, compared with 8.8% of those with normal gamma globulin levels. Rates of serious infection, as indicated by the ratio of low to normal levels for IgM, were 11.8%:8.1% while the rates for IgG were 15.1%:8.2%.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Gottenberg reported a relevant financial relationship with Roche.

* Clarification: This story was updated on 12/12/2011.

NEW YORK – The low levels of immunoglobulin G seen in a group of patients receiving rituximab for rheumatoid arthritis were associated with a twofold increased risk of serious infections, judging from the results of a 5-year prospective French register of 2,000 patients, according to Dr. Yusuf Yazici.

“These results give us one piece of evidence to support what investigators have long suspected: Low IgG levels may increase risk of infections,” said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the New York University Hospital for Joint Diseases.*

Of the risk factors investigated by Dr. Jacques-Eric Gottenberg of the Strasbourg (France) University Hospital and his associates, only low serum IgG levels – not gamma globulin or immunoglobulin M (IgM) levels – were associated with serious infections in rheumatoid arthritis (RA) patients treated with rituximab, according to Dr. Yazici. This finding suggests that serum IgG levels in particular should be checked before each new cycle of rituximab and that the risk/benefit ratio of rituximab should be carefully assessed for those with low IgG levels. A therapy other than rituximab should be considered for patients with low immunoglobulin G (IgG) levels who already have a severe infection or severe comorbidities, according to Dr. Gottenberg’s findings.

The French AIR (Autoimmunity and Rituximab) Registry is a 5-year, prospective, multicenter study begun in 2006 that prospectively collects data on patients treated with rituximab on and off label for refractory arthritides. It is thought to be the largest prospective study, based on a national registry, focusing on severe infections in RA patients treated with rituximab in a clinical setting. Many patients have comorbidities, such as cancer, chronic lung disease, cardiac insufficiency, or diabetes. A nationwide initiative, most patients were registered from rheumatology departments while less than 10% originated from internal medicine departments. The 88 centers who participated in the register write more than 85% of all rituximab prescriptions in France for nonhematologic, nononcologic indications.

"You can’t suppress IgG levels forever without expecting some increase in infections."

Since this was a noninterventional study, no laboratory exams were required either at baseline or after rituximab treatment. Even though immunoglobulin levels are not routinely assessed during rituximab therapy, of the 2000 patients with RA included in the AIR Registry, gamma globulin, IgM, or IgG levels after rituximab treatment had been collected in almost 60% of enrolled patients. Of those who had undergone these analyses, 15.5% had low levels of serum gamma globulin less than 6 g/L), 26.6% had low levels of IgM less than 0.5 g/L) and 12.1% had low IgG levels (less than 6 g/L).

The authors looked at the rates of serious infections (defined as an infection occurring during the 12 months following each infusion of rituximab that required hospitalization and/or intravenous antibiotics and/or resulted in death) in patients with normal and low levels of gamma globulin, IgM, or IgG. Univariate analysis adjusted according to follow-up duration revealed that only low IgG levels after rituximab were associated with a significantly increased risk of serious infections, with almost a twofold increase in risk (odds ratio, 1.99; 95% confidence interval, 1.2-3.3; P = .008). No significant effects were found for low levels of gamma globulin (OR, 1.5; 95% CI, 0.9-2.5; P = .09) or IgM (OR, 1.5; 95% CI, 0.9-2.3; P = .08).

In a multivariate analysis, when the researchers adjusted for older age, previous cancer, or serious or recurrent infections, only low IgG after rituximab remained associated with serious infections. In published work, Dr. Gottenberg reported that chronic lung disease and/or cardiac insufficiency and extraarticular involvement also rendered RA patients treated with rituximab more prone to severe infections (Arthritis Rheum. 2010;62[9]:2625-32).

For all measures serious infections were more frequent in those with lower levels of immunologic indices. For instance, 13.5% of patients with low gamma globulin levels after rituximab had serious infections, compared with 8.8% of those with normal gamma globulin levels. Rates of serious infection, as indicated by the ratio of low to normal levels for IgM, were 11.8%:8.1% while the rates for IgG were 15.1%:8.2%.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Gottenberg reported a relevant financial relationship with Roche.

* Clarification: This story was updated on 12/12/2011.

NEW YORK – The low levels of immunoglobulin G seen in a group of patients receiving rituximab for rheumatoid arthritis were associated with a twofold increased risk of serious infections, judging from the results of a 5-year prospective French register of 2,000 patients, according to Dr. Yusuf Yazici.

“These results give us one piece of evidence to support what investigators have long suspected: Low IgG levels may increase risk of infections,” said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the New York University Hospital for Joint Diseases.*

Of the risk factors investigated by Dr. Jacques-Eric Gottenberg of the Strasbourg (France) University Hospital and his associates, only low serum IgG levels – not gamma globulin or immunoglobulin M (IgM) levels – were associated with serious infections in rheumatoid arthritis (RA) patients treated with rituximab, according to Dr. Yazici. This finding suggests that serum IgG levels in particular should be checked before each new cycle of rituximab and that the risk/benefit ratio of rituximab should be carefully assessed for those with low IgG levels. A therapy other than rituximab should be considered for patients with low immunoglobulin G (IgG) levels who already have a severe infection or severe comorbidities, according to Dr. Gottenberg’s findings.

The French AIR (Autoimmunity and Rituximab) Registry is a 5-year, prospective, multicenter study begun in 2006 that prospectively collects data on patients treated with rituximab on and off label for refractory arthritides. It is thought to be the largest prospective study, based on a national registry, focusing on severe infections in RA patients treated with rituximab in a clinical setting. Many patients have comorbidities, such as cancer, chronic lung disease, cardiac insufficiency, or diabetes. A nationwide initiative, most patients were registered from rheumatology departments while less than 10% originated from internal medicine departments. The 88 centers who participated in the register write more than 85% of all rituximab prescriptions in France for nonhematologic, nononcologic indications.

"You can’t suppress IgG levels forever without expecting some increase in infections."

Since this was a noninterventional study, no laboratory exams were required either at baseline or after rituximab treatment. Even though immunoglobulin levels are not routinely assessed during rituximab therapy, of the 2000 patients with RA included in the AIR Registry, gamma globulin, IgM, or IgG levels after rituximab treatment had been collected in almost 60% of enrolled patients. Of those who had undergone these analyses, 15.5% had low levels of serum gamma globulin less than 6 g/L), 26.6% had low levels of IgM less than 0.5 g/L) and 12.1% had low IgG levels (less than 6 g/L).

The authors looked at the rates of serious infections (defined as an infection occurring during the 12 months following each infusion of rituximab that required hospitalization and/or intravenous antibiotics and/or resulted in death) in patients with normal and low levels of gamma globulin, IgM, or IgG. Univariate analysis adjusted according to follow-up duration revealed that only low IgG levels after rituximab were associated with a significantly increased risk of serious infections, with almost a twofold increase in risk (odds ratio, 1.99; 95% confidence interval, 1.2-3.3; P = .008). No significant effects were found for low levels of gamma globulin (OR, 1.5; 95% CI, 0.9-2.5; P = .09) or IgM (OR, 1.5; 95% CI, 0.9-2.3; P = .08).

In a multivariate analysis, when the researchers adjusted for older age, previous cancer, or serious or recurrent infections, only low IgG after rituximab remained associated with serious infections. In published work, Dr. Gottenberg reported that chronic lung disease and/or cardiac insufficiency and extraarticular involvement also rendered RA patients treated with rituximab more prone to severe infections (Arthritis Rheum. 2010;62[9]:2625-32).

For all measures serious infections were more frequent in those with lower levels of immunologic indices. For instance, 13.5% of patients with low gamma globulin levels after rituximab had serious infections, compared with 8.8% of those with normal gamma globulin levels. Rates of serious infection, as indicated by the ratio of low to normal levels for IgM, were 11.8%:8.1% while the rates for IgG were 15.1%:8.2%.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Gottenberg reported a relevant financial relationship with Roche.

* Clarification: This story was updated on 12/12/2011.

PROVIDENCE, R.I. – A short course of the urinary antibiotic nitrofurantoin after midurethral sling placement for stress urinary incontinence reduced the incidence of postprocedure urinary tract infection by nearly 50%, reported Dr. Daniel Jackson.

“In the last 10 years, the literature has shown that the incidence of UTIs after sling placement ranges from 8.9% to 34%,” according to Dr. Jackson of the University of Missouri–Columbia.

“We asked whether the incidence of postoperative bladder infection related to midurethral sling placement could be significantly reduced by a short course of a common, inexpensive urinary antibiotic,” he said.

In this prospective, double-blind study, 159 women from two academic medical centers scheduled to undergo outpatient vaginal surgery for stress incontinence were randomized to receive either nitrofurantoin (100 mg twice daily) or placebo for 3 days after surgery.

Data were analyzed from 74 women who received an antibiotic and 75 women who received placebo. All patients received preoperative treatment with a third-generation cephalosporin, Dr. Jackson explained.

At the 6-week visit, a positive diagnosis depended on a positive review of systems for dysuria and frequency and a negative review of systems for vaginal discharge or irritation, as well as a positive urine dip and urine culture, he reported.

Almost one-quarter of women who underwent midurethral sling placement (n = 37/149, 24.8%) were diagnosed with a UTI during the study period.

Treatment with an antibiotic significantly reduced the incidence of UTIs, from 32% in the placebo group to 17.6% in the nitrofurantoin group.

Multivariate analysis indicated that two variables, antibiotic use and no postoperative catheter use, were independently associated with a reduced risk of UTI development, Dr. Jackson commented.

No adverse events were reported in this study.

In response to a question from the audience, Dr. Jackson said that the choice of antibiotic, nitrofurantoin, was based on its cost and his institution's preferences, but he said he had no definitive evidence regarding whether other urinary antibiotics would produce comparable or better results.

PROVIDENCE, R.I. – A short course of the urinary antibiotic nitrofurantoin after midurethral sling placement for stress urinary incontinence reduced the incidence of postprocedure urinary tract infection by nearly 50%, reported Dr. Daniel Jackson.

“In the last 10 years, the literature has shown that the incidence of UTIs after sling placement ranges from 8.9% to 34%,” according to Dr. Jackson of the University of Missouri–Columbia.

“We asked whether the incidence of postoperative bladder infection related to midurethral sling placement could be significantly reduced by a short course of a common, inexpensive urinary antibiotic,” he said.

In this prospective, double-blind study, 159 women from two academic medical centers scheduled to undergo outpatient vaginal surgery for stress incontinence were randomized to receive either nitrofurantoin (100 mg twice daily) or placebo for 3 days after surgery.

Data were analyzed from 74 women who received an antibiotic and 75 women who received placebo. All patients received preoperative treatment with a third-generation cephalosporin, Dr. Jackson explained.

At the 6-week visit, a positive diagnosis depended on a positive review of systems for dysuria and frequency and a negative review of systems for vaginal discharge or irritation, as well as a positive urine dip and urine culture, he reported.

Almost one-quarter of women who underwent midurethral sling placement (n = 37/149, 24.8%) were diagnosed with a UTI during the study period.

Treatment with an antibiotic significantly reduced the incidence of UTIs, from 32% in the placebo group to 17.6% in the nitrofurantoin group.

Multivariate analysis indicated that two variables, antibiotic use and no postoperative catheter use, were independently associated with a reduced risk of UTI development, Dr. Jackson commented.

No adverse events were reported in this study.

In response to a question from the audience, Dr. Jackson said that the choice of antibiotic, nitrofurantoin, was based on its cost and his institution's preferences, but he said he had no definitive evidence regarding whether other urinary antibiotics would produce comparable or better results.

PROVIDENCE, R.I. – A short course of the urinary antibiotic nitrofurantoin after midurethral sling placement for stress urinary incontinence reduced the incidence of postprocedure urinary tract infection by nearly 50%, reported Dr. Daniel Jackson.

“In the last 10 years, the literature has shown that the incidence of UTIs after sling placement ranges from 8.9% to 34%,” according to Dr. Jackson of the University of Missouri–Columbia.

“We asked whether the incidence of postoperative bladder infection related to midurethral sling placement could be significantly reduced by a short course of a common, inexpensive urinary antibiotic,” he said.

In this prospective, double-blind study, 159 women from two academic medical centers scheduled to undergo outpatient vaginal surgery for stress incontinence were randomized to receive either nitrofurantoin (100 mg twice daily) or placebo for 3 days after surgery.

Data were analyzed from 74 women who received an antibiotic and 75 women who received placebo. All patients received preoperative treatment with a third-generation cephalosporin, Dr. Jackson explained.

At the 6-week visit, a positive diagnosis depended on a positive review of systems for dysuria and frequency and a negative review of systems for vaginal discharge or irritation, as well as a positive urine dip and urine culture, he reported.

Almost one-quarter of women who underwent midurethral sling placement (n = 37/149, 24.8%) were diagnosed with a UTI during the study period.

Treatment with an antibiotic significantly reduced the incidence of UTIs, from 32% in the placebo group to 17.6% in the nitrofurantoin group.

Multivariate analysis indicated that two variables, antibiotic use and no postoperative catheter use, were independently associated with a reduced risk of UTI development, Dr. Jackson commented.

No adverse events were reported in this study.

In response to a question from the audience, Dr. Jackson said that the choice of antibiotic, nitrofurantoin, was based on its cost and his institution's preferences, but he said he had no definitive evidence regarding whether other urinary antibiotics would produce comparable or better results.

PROVIDENCE, R.I. – A postpartum perineal clinic staffed by urogynecologists has been established at the University of Michigan to expedite the assessment and treatment of pelvic floor disorders resulting from maternal birth injuries, according to Dr. Cynthia Brincat, who described the clinic in an oral poster presentation at the meeting.

“About 10% of women develop complications associated with childbirth. We are a one-stop location for these women to be seen during a very busy and very stressful time in their lives,” Dr. Brincat said in an interview. “We provide focused, problem-based, short-term therapy. Patients then can go back to their regular providers, often with a care plan that can be carried out in that setting.” Dr. Brincat worked at the clinic as a fellow in female pelvic medicine and reconstructive surgery at the University of Michigan Medical Center, and is now with the University of Wisconsin–Madison.

At the Michigan Healthy Healing After Delivery Program, patients are seen within 2 weeks of requesting an appointment. It offers its services to women with such symptoms as fecal or urinary incontinence, painful or nonhealing episiotomy, anal fissures, third- or fourth-degree lacerations, rectovaginal fistulas, postpartum urinary retention, pelvic organ prolapse, and painful intercourse.

The clinic provides a range of services. “Some of the treatments we provide center around asking the right questions and uncovering what is going on. We do a lot of patient education. Once a patient understands what has happened to her, she can take better care of herself,” said Dr. Brincat. “For example, if she has a third- or fourth-degree laceration, she can understand how important it is to keep her stool consistency soft.” Patients can consult with a PhD nurse continence expert and physical therapists who can develop a pelvic floor muscle-strengthening program or provide advice concerning diet and lifestyle changes to promote healthy living and prevent future incontinence problems. Counseling in the clinic deals with the patient's emotional well-being and fears about future pregnancies.

More focused interventions include cauterization of granulation tissue, application of nitroglycerin paste for anal fissures, trigger-point injections for pain relief, or estrogen application for atrophic vaginal tissue. Biofeedback is commonly used for helping patients visualize the most effective ways to perform pelvic floor muscle contraction exercises. Other services provided include endoanal ultrasound for the assessment of sphincter anatomy and multichannel urodynamics to assess bladder function. MRI studies, performed under approved research protocols, are useful for detailing birth trauma such as injury to the levator ani and can help physicians establish a plan for avoiding injuries with subsequent births. Some patients require surgical management for incontinence, anal sphincter repair, or debridement.

Now in its fourth year, the practice has been steadily growing. Total new patient visits increased 35% from year 1 to year 2 (from 40 to 62) and 7.5% between year 2 and year 3 (62 to 66). “This year we are on track to see 80 new patients,” said Dr. Brincat. The most common presenting problems were follow-up of third-degree lacerations, urinary incontinence, and perineal pain.

Analysis of referral distribution indicated that less than one-third of referrals were from the University of Michigan's in-house generalist practice. Thirty-one percent came from the resident practice, and 41% were referred from family medicine practice, certified nurse-midwife practice, outside physician referrals, and self-referrals.

“We knew we had to build a broad referral base to be successful,” said Dr. Brincat. To accomplish this, the nurse coordinator and staff members undertook direct patient marketing via Web search engines, YouTube videos, podcasts, and distribution of printed patient education materials. Peer-to-peer programs targeted nurses and other obstetric providers. All referrals are cleared through one point of entry, a knowledgeable nurse who can triage patients and serve as an ongoing contact.

Although there was some initial reluctance among generalists to refer patients, that no longer holds true. “Patients often don't see us more than once – our average number of visits is about 1.6,” said Dr. Brincat. Once a primary provider sees that the patient returns to his or her practice, the provider is less reluctant to refer the next patient. In fact, she said, the bond with the primary provider is often strengthened once the patient realizes that the provider values the patient's outcome enough to send the patient for specialized treatment when necessary.

“In the United Kingdom and most European countries, anyone who hasundergone a traumatic birth injury is seen in a follow-up clinic right away. In the United States, that's not the standard of care. What we're trying to do is change that,” said Dr. Brincat. “In general, the assessment and treatment of women with birth injuries is not given enough attention. If this was about professional football players or baseball players, and we said 1 in 10 of them would experience a traumatic injury and not be seen for weeks afterwards, I think the issue would get a lot more attention.”

Dr. Brincat said she had no relevant financial disclosures.

PROVIDENCE, R.I. – A postpartum perineal clinic staffed by urogynecologists has been established at the University of Michigan to expedite the assessment and treatment of pelvic floor disorders resulting from maternal birth injuries, according to Dr. Cynthia Brincat, who described the clinic in an oral poster presentation at the meeting.

“About 10% of women develop complications associated with childbirth. We are a one-stop location for these women to be seen during a very busy and very stressful time in their lives,” Dr. Brincat said in an interview. “We provide focused, problem-based, short-term therapy. Patients then can go back to their regular providers, often with a care plan that can be carried out in that setting.” Dr. Brincat worked at the clinic as a fellow in female pelvic medicine and reconstructive surgery at the University of Michigan Medical Center, and is now with the University of Wisconsin–Madison.

At the Michigan Healthy Healing After Delivery Program, patients are seen within 2 weeks of requesting an appointment. It offers its services to women with such symptoms as fecal or urinary incontinence, painful or nonhealing episiotomy, anal fissures, third- or fourth-degree lacerations, rectovaginal fistulas, postpartum urinary retention, pelvic organ prolapse, and painful intercourse.

The clinic provides a range of services. “Some of the treatments we provide center around asking the right questions and uncovering what is going on. We do a lot of patient education. Once a patient understands what has happened to her, she can take better care of herself,” said Dr. Brincat. “For example, if she has a third- or fourth-degree laceration, she can understand how important it is to keep her stool consistency soft.” Patients can consult with a PhD nurse continence expert and physical therapists who can develop a pelvic floor muscle-strengthening program or provide advice concerning diet and lifestyle changes to promote healthy living and prevent future incontinence problems. Counseling in the clinic deals with the patient's emotional well-being and fears about future pregnancies.

More focused interventions include cauterization of granulation tissue, application of nitroglycerin paste for anal fissures, trigger-point injections for pain relief, or estrogen application for atrophic vaginal tissue. Biofeedback is commonly used for helping patients visualize the most effective ways to perform pelvic floor muscle contraction exercises. Other services provided include endoanal ultrasound for the assessment of sphincter anatomy and multichannel urodynamics to assess bladder function. MRI studies, performed under approved research protocols, are useful for detailing birth trauma such as injury to the levator ani and can help physicians establish a plan for avoiding injuries with subsequent births. Some patients require surgical management for incontinence, anal sphincter repair, or debridement.

Now in its fourth year, the practice has been steadily growing. Total new patient visits increased 35% from year 1 to year 2 (from 40 to 62) and 7.5% between year 2 and year 3 (62 to 66). “This year we are on track to see 80 new patients,” said Dr. Brincat. The most common presenting problems were follow-up of third-degree lacerations, urinary incontinence, and perineal pain.

Analysis of referral distribution indicated that less than one-third of referrals were from the University of Michigan's in-house generalist practice. Thirty-one percent came from the resident practice, and 41% were referred from family medicine practice, certified nurse-midwife practice, outside physician referrals, and self-referrals.

“We knew we had to build a broad referral base to be successful,” said Dr. Brincat. To accomplish this, the nurse coordinator and staff members undertook direct patient marketing via Web search engines, YouTube videos, podcasts, and distribution of printed patient education materials. Peer-to-peer programs targeted nurses and other obstetric providers. All referrals are cleared through one point of entry, a knowledgeable nurse who can triage patients and serve as an ongoing contact.

Although there was some initial reluctance among generalists to refer patients, that no longer holds true. “Patients often don't see us more than once – our average number of visits is about 1.6,” said Dr. Brincat. Once a primary provider sees that the patient returns to his or her practice, the provider is less reluctant to refer the next patient. In fact, she said, the bond with the primary provider is often strengthened once the patient realizes that the provider values the patient's outcome enough to send the patient for specialized treatment when necessary.

“In the United Kingdom and most European countries, anyone who hasundergone a traumatic birth injury is seen in a follow-up clinic right away. In the United States, that's not the standard of care. What we're trying to do is change that,” said Dr. Brincat. “In general, the assessment and treatment of women with birth injuries is not given enough attention. If this was about professional football players or baseball players, and we said 1 in 10 of them would experience a traumatic injury and not be seen for weeks afterwards, I think the issue would get a lot more attention.”

Dr. Brincat said she had no relevant financial disclosures.

PROVIDENCE, R.I. – A postpartum perineal clinic staffed by urogynecologists has been established at the University of Michigan to expedite the assessment and treatment of pelvic floor disorders resulting from maternal birth injuries, according to Dr. Cynthia Brincat, who described the clinic in an oral poster presentation at the meeting.

“About 10% of women develop complications associated with childbirth. We are a one-stop location for these women to be seen during a very busy and very stressful time in their lives,” Dr. Brincat said in an interview. “We provide focused, problem-based, short-term therapy. Patients then can go back to their regular providers, often with a care plan that can be carried out in that setting.” Dr. Brincat worked at the clinic as a fellow in female pelvic medicine and reconstructive surgery at the University of Michigan Medical Center, and is now with the University of Wisconsin–Madison.

At the Michigan Healthy Healing After Delivery Program, patients are seen within 2 weeks of requesting an appointment. It offers its services to women with such symptoms as fecal or urinary incontinence, painful or nonhealing episiotomy, anal fissures, third- or fourth-degree lacerations, rectovaginal fistulas, postpartum urinary retention, pelvic organ prolapse, and painful intercourse.

The clinic provides a range of services. “Some of the treatments we provide center around asking the right questions and uncovering what is going on. We do a lot of patient education. Once a patient understands what has happened to her, she can take better care of herself,” said Dr. Brincat. “For example, if she has a third- or fourth-degree laceration, she can understand how important it is to keep her stool consistency soft.” Patients can consult with a PhD nurse continence expert and physical therapists who can develop a pelvic floor muscle-strengthening program or provide advice concerning diet and lifestyle changes to promote healthy living and prevent future incontinence problems. Counseling in the clinic deals with the patient's emotional well-being and fears about future pregnancies.

More focused interventions include cauterization of granulation tissue, application of nitroglycerin paste for anal fissures, trigger-point injections for pain relief, or estrogen application for atrophic vaginal tissue. Biofeedback is commonly used for helping patients visualize the most effective ways to perform pelvic floor muscle contraction exercises. Other services provided include endoanal ultrasound for the assessment of sphincter anatomy and multichannel urodynamics to assess bladder function. MRI studies, performed under approved research protocols, are useful for detailing birth trauma such as injury to the levator ani and can help physicians establish a plan for avoiding injuries with subsequent births. Some patients require surgical management for incontinence, anal sphincter repair, or debridement.

Now in its fourth year, the practice has been steadily growing. Total new patient visits increased 35% from year 1 to year 2 (from 40 to 62) and 7.5% between year 2 and year 3 (62 to 66). “This year we are on track to see 80 new patients,” said Dr. Brincat. The most common presenting problems were follow-up of third-degree lacerations, urinary incontinence, and perineal pain.

Analysis of referral distribution indicated that less than one-third of referrals were from the University of Michigan's in-house generalist practice. Thirty-one percent came from the resident practice, and 41% were referred from family medicine practice, certified nurse-midwife practice, outside physician referrals, and self-referrals.

“We knew we had to build a broad referral base to be successful,” said Dr. Brincat. To accomplish this, the nurse coordinator and staff members undertook direct patient marketing via Web search engines, YouTube videos, podcasts, and distribution of printed patient education materials. Peer-to-peer programs targeted nurses and other obstetric providers. All referrals are cleared through one point of entry, a knowledgeable nurse who can triage patients and serve as an ongoing contact.

Although there was some initial reluctance among generalists to refer patients, that no longer holds true. “Patients often don't see us more than once – our average number of visits is about 1.6,” said Dr. Brincat. Once a primary provider sees that the patient returns to his or her practice, the provider is less reluctant to refer the next patient. In fact, she said, the bond with the primary provider is often strengthened once the patient realizes that the provider values the patient's outcome enough to send the patient for specialized treatment when necessary.

“In the United Kingdom and most European countries, anyone who hasundergone a traumatic birth injury is seen in a follow-up clinic right away. In the United States, that's not the standard of care. What we're trying to do is change that,” said Dr. Brincat. “In general, the assessment and treatment of women with birth injuries is not given enough attention. If this was about professional football players or baseball players, and we said 1 in 10 of them would experience a traumatic injury and not be seen for weeks afterwards, I think the issue would get a lot more attention.”

Dr. Brincat said she had no relevant financial disclosures.

PROVIDENCE, R.I. – Vitamin D levels were significantly lower in women diagnosed with a pelvic floor disorder than in a comparison group of gynecology patients without pelvic floor disorders, based on a retrospective chart review of patients seen at a urogynecology care clinic between 2008 and 2010.

In the study, 550 patients had both a clinic visit and an assessment of vitamin D levels, but 156 were excluded from consideration because of missing clinical data (n = 137), stage III or greater kidney disease (n = 17), or other medical conditions (n = 2).

Of the 394 remaining patients, 268 had at least one pelvic floor disorder (PFD).

The most common diagnoses were pelvic organ prolapse (49%) and mixed urinary incontinence (30%).

In the “benign gynecologic” group used for comparison, 126 women were seen for routine gynecologic exams but were not diagnosed with any PFD.

The women with PFDs were older (64.3 years vs. 60.2 years), and included a greater percentage of blacks (40% vs. 20%), reported Dr. Candace Y. Parker-Autry, who presented the findings as a poster at the meeting.

Total mean 25(OH)D levels were 29.3 ng/mL in women with PFDs and 35.0 ng/mL in women without PFDs, a significant difference.

Among women with PFDs, 51.5% had insufficient or deficient vitamin D levels with mean 25(OH)D levels of 18.6 ng/mL and 48.5% were found to be vitamin D sufficient with mean 25(OH)D levels of 38.4 ng/mL (P = .001).

Women who had PFDs and were vitamin D sufficient were significantly more likely to have taken vitamin D and calcium supplements. Vitamin D insufficiency was defined as levels between 15 ng/mL and 29 ng/mL; levels below 15 ng/mL were deemed deficient.

Some racial disparity was noted. Vitamin D insufficiency/deficiency was noted in 50% of non-Hispanic whites and in 68% of black women with PFDs.

Approximately 73% of U.S. adults and 80% of reproductive aged women have insufficient vitamin D levels, according to Dr. Parker-Autry, who is affiliated with the division of urogynecology and pelvic reconstructive surgery at the University of Alabama at Birmingham.

The question remains whether vitamin D insufficiency contributes to pelvic muscle weakness and PFDs.

At baseline, women in the PFD gro up were asked to complete three validated questionnaires, assessing the impact of their symptoms on quality of life, including the Pelvic Floor Distress Inventory and its three subscales: Pelvic Organ Prolapse Distress Severity (POPDI-6), the Colorectal-Anal Distress Inventory (CRDAI-8), and the Urogenital Distress Inventory for Incontinence (UDI-6); the Medical, Epidemiologic, and Social Aspects of Aging (MESA) questionnaire, and the Incontinence Impact Questionnaire (IIQ-7).

After controlling for confounding variables, vitamin D insufficiency was associated with a greater negative impact from urinary incontinence symptoms (P = .001 on the IIQ-7) but there were no other significant differences regarding other pelvic or colorectal symptoms.

PROVIDENCE, R.I. – Vitamin D levels were significantly lower in women diagnosed with a pelvic floor disorder than in a comparison group of gynecology patients without pelvic floor disorders, based on a retrospective chart review of patients seen at a urogynecology care clinic between 2008 and 2010.

In the study, 550 patients had both a clinic visit and an assessment of vitamin D levels, but 156 were excluded from consideration because of missing clinical data (n = 137), stage III or greater kidney disease (n = 17), or other medical conditions (n = 2).

Of the 394 remaining patients, 268 had at least one pelvic floor disorder (PFD).

The most common diagnoses were pelvic organ prolapse (49%) and mixed urinary incontinence (30%).

In the “benign gynecologic” group used for comparison, 126 women were seen for routine gynecologic exams but were not diagnosed with any PFD.

The women with PFDs were older (64.3 years vs. 60.2 years), and included a greater percentage of blacks (40% vs. 20%), reported Dr. Candace Y. Parker-Autry, who presented the findings as a poster at the meeting.

Total mean 25(OH)D levels were 29.3 ng/mL in women with PFDs and 35.0 ng/mL in women without PFDs, a significant difference.

Among women with PFDs, 51.5% had insufficient or deficient vitamin D levels with mean 25(OH)D levels of 18.6 ng/mL and 48.5% were found to be vitamin D sufficient with mean 25(OH)D levels of 38.4 ng/mL (P = .001).

Women who had PFDs and were vitamin D sufficient were significantly more likely to have taken vitamin D and calcium supplements. Vitamin D insufficiency was defined as levels between 15 ng/mL and 29 ng/mL; levels below 15 ng/mL were deemed deficient.

Some racial disparity was noted. Vitamin D insufficiency/deficiency was noted in 50% of non-Hispanic whites and in 68% of black women with PFDs.

Approximately 73% of U.S. adults and 80% of reproductive aged women have insufficient vitamin D levels, according to Dr. Parker-Autry, who is affiliated with the division of urogynecology and pelvic reconstructive surgery at the University of Alabama at Birmingham.

The question remains whether vitamin D insufficiency contributes to pelvic muscle weakness and PFDs.

At baseline, women in the PFD gro up were asked to complete three validated questionnaires, assessing the impact of their symptoms on quality of life, including the Pelvic Floor Distress Inventory and its three subscales: Pelvic Organ Prolapse Distress Severity (POPDI-6), the Colorectal-Anal Distress Inventory (CRDAI-8), and the Urogenital Distress Inventory for Incontinence (UDI-6); the Medical, Epidemiologic, and Social Aspects of Aging (MESA) questionnaire, and the Incontinence Impact Questionnaire (IIQ-7).

After controlling for confounding variables, vitamin D insufficiency was associated with a greater negative impact from urinary incontinence symptoms (P = .001 on the IIQ-7) but there were no other significant differences regarding other pelvic or colorectal symptoms.

PROVIDENCE, R.I. – Vitamin D levels were significantly lower in women diagnosed with a pelvic floor disorder than in a comparison group of gynecology patients without pelvic floor disorders, based on a retrospective chart review of patients seen at a urogynecology care clinic between 2008 and 2010.

In the study, 550 patients had both a clinic visit and an assessment of vitamin D levels, but 156 were excluded from consideration because of missing clinical data (n = 137), stage III or greater kidney disease (n = 17), or other medical conditions (n = 2).

Of the 394 remaining patients, 268 had at least one pelvic floor disorder (PFD).

The most common diagnoses were pelvic organ prolapse (49%) and mixed urinary incontinence (30%).

In the “benign gynecologic” group used for comparison, 126 women were seen for routine gynecologic exams but were not diagnosed with any PFD.

The women with PFDs were older (64.3 years vs. 60.2 years), and included a greater percentage of blacks (40% vs. 20%), reported Dr. Candace Y. Parker-Autry, who presented the findings as a poster at the meeting.

Total mean 25(OH)D levels were 29.3 ng/mL in women with PFDs and 35.0 ng/mL in women without PFDs, a significant difference.

Among women with PFDs, 51.5% had insufficient or deficient vitamin D levels with mean 25(OH)D levels of 18.6 ng/mL and 48.5% were found to be vitamin D sufficient with mean 25(OH)D levels of 38.4 ng/mL (P = .001).

Women who had PFDs and were vitamin D sufficient were significantly more likely to have taken vitamin D and calcium supplements. Vitamin D insufficiency was defined as levels between 15 ng/mL and 29 ng/mL; levels below 15 ng/mL were deemed deficient.

Some racial disparity was noted. Vitamin D insufficiency/deficiency was noted in 50% of non-Hispanic whites and in 68% of black women with PFDs.

Approximately 73% of U.S. adults and 80% of reproductive aged women have insufficient vitamin D levels, according to Dr. Parker-Autry, who is affiliated with the division of urogynecology and pelvic reconstructive surgery at the University of Alabama at Birmingham.

The question remains whether vitamin D insufficiency contributes to pelvic muscle weakness and PFDs.

At baseline, women in the PFD gro up were asked to complete three validated questionnaires, assessing the impact of their symptoms on quality of life, including the Pelvic Floor Distress Inventory and its three subscales: Pelvic Organ Prolapse Distress Severity (POPDI-6), the Colorectal-Anal Distress Inventory (CRDAI-8), and the Urogenital Distress Inventory for Incontinence (UDI-6); the Medical, Epidemiologic, and Social Aspects of Aging (MESA) questionnaire, and the Incontinence Impact Questionnaire (IIQ-7).

After controlling for confounding variables, vitamin D insufficiency was associated with a greater negative impact from urinary incontinence symptoms (P = .001 on the IIQ-7) but there were no other significant differences regarding other pelvic or colorectal symptoms.

PROVIDENCE, R.I. – More than a quarter of patients with multiple sclerosis report either current or previous urinary catheterization, with significantly higher rates reported for males than females, according to a survey of more than 9,600 patients.

"Although the development of voiding dysfunction and catheter use is common among patients with MS, rates of catheter use in this population was previously unknown," said Dr. Sangeeta T. Mahajan, division chief of female pelvic medicine and reconstructive surgery at University Hospitals, Case Medical Center (Cleveland).

Dr. Mahajan analyzed results from the Fall 2005 NARCOMS (North American Research Committee on Multiple Sclerosis) registry, which mailed surveys to 16,858 patients with MS. A total of 58% returned the survey and 26 patients were excluded because of prior major bladder surgery, leaving 9,676 responses. The group was primarily white (93%) and female (75%).

The survey revealed that 2,514 (26%) used a catheter at times, with 11% reporting current catheter use and 15% past use only. One-third of men had used a catheter, significantly more than did women (32% vs. 24%, P less than .001). Those who catheterized tended to have a longer history of MS (17.1 vs. 12.1 years, P less than .001); were more disabled, as measured by the PDDS (Patient Determined Disease Steps) scale; and had poorer quality of life, as measured by the SF-12 (Short Form–12 Quality of Life) inventory (P less than .001 in all components), she reported in a poster at the annual meeting of the American Urogynecologic Society.

The preferred method of catheterization differed between men and women. Men tended to prefer indwelling methods such as transurethral Foley catheterization (TFC) (47% males vs. 41% females, P = .003) or suprapubic catheterization (SPC) (12% vs. 6%, respectively, P less than .001). Overall, the most common methods of catheterization were intermittent self-catheterization (81%), followed by TFC (43%) and SPC (8%).

Overactive bladder symptoms, as indicated by a score of greater than 1 on the UDI-6 (Urogenital Distress Inventory), were more severe in those who catheterized (P less than .001). The exception was for severe nocturia, which was more frequent in those who did not catheterize.

Only 44% of the respondents had undergone urologic evaluation, including urodynamic testing (21%) and post-void residual screening (26%). Overall, 37% were prescribed an anticholinergic medication, although this percentage increased to 55% for those who catheterized (compared with 30% of those who did not catheterize, P less than .001). The medications used were generally older anticholinergics such as oxybutynin and tolterodine. A small fraction had undergone sacral neuromodulation (0.3%) or intradetrusor injection with onabotulinumtoxinA (0.9%).

Dr. Mahajan indicated she had no relevant disclosures.

PROVIDENCE, R.I. – More than a quarter of patients with multiple sclerosis report either current or previous urinary catheterization, with significantly higher rates reported for males than females, according to a survey of more than 9,600 patients.

"Although the development of voiding dysfunction and catheter use is common among patients with MS, rates of catheter use in this population was previously unknown," said Dr. Sangeeta T. Mahajan, division chief of female pelvic medicine and reconstructive surgery at University Hospitals, Case Medical Center (Cleveland).

Dr. Mahajan analyzed results from the Fall 2005 NARCOMS (North American Research Committee on Multiple Sclerosis) registry, which mailed surveys to 16,858 patients with MS. A total of 58% returned the survey and 26 patients were excluded because of prior major bladder surgery, leaving 9,676 responses. The group was primarily white (93%) and female (75%).

The survey revealed that 2,514 (26%) used a catheter at times, with 11% reporting current catheter use and 15% past use only. One-third of men had used a catheter, significantly more than did women (32% vs. 24%, P less than .001). Those who catheterized tended to have a longer history of MS (17.1 vs. 12.1 years, P less than .001); were more disabled, as measured by the PDDS (Patient Determined Disease Steps) scale; and had poorer quality of life, as measured by the SF-12 (Short Form–12 Quality of Life) inventory (P less than .001 in all components), she reported in a poster at the annual meeting of the American Urogynecologic Society.

The preferred method of catheterization differed between men and women. Men tended to prefer indwelling methods such as transurethral Foley catheterization (TFC) (47% males vs. 41% females, P = .003) or suprapubic catheterization (SPC) (12% vs. 6%, respectively, P less than .001). Overall, the most common methods of catheterization were intermittent self-catheterization (81%), followed by TFC (43%) and SPC (8%).

Overactive bladder symptoms, as indicated by a score of greater than 1 on the UDI-6 (Urogenital Distress Inventory), were more severe in those who catheterized (P less than .001). The exception was for severe nocturia, which was more frequent in those who did not catheterize.

Only 44% of the respondents had undergone urologic evaluation, including urodynamic testing (21%) and post-void residual screening (26%). Overall, 37% were prescribed an anticholinergic medication, although this percentage increased to 55% for those who catheterized (compared with 30% of those who did not catheterize, P less than .001). The medications used were generally older anticholinergics such as oxybutynin and tolterodine. A small fraction had undergone sacral neuromodulation (0.3%) or intradetrusor injection with onabotulinumtoxinA (0.9%).

Dr. Mahajan indicated she had no relevant disclosures.

PROVIDENCE, R.I. – More than a quarter of patients with multiple sclerosis report either current or previous urinary catheterization, with significantly higher rates reported for males than females, according to a survey of more than 9,600 patients.

"Although the development of voiding dysfunction and catheter use is common among patients with MS, rates of catheter use in this population was previously unknown," said Dr. Sangeeta T. Mahajan, division chief of female pelvic medicine and reconstructive surgery at University Hospitals, Case Medical Center (Cleveland).

Dr. Mahajan analyzed results from the Fall 2005 NARCOMS (North American Research Committee on Multiple Sclerosis) registry, which mailed surveys to 16,858 patients with MS. A total of 58% returned the survey and 26 patients were excluded because of prior major bladder surgery, leaving 9,676 responses. The group was primarily white (93%) and female (75%).

The survey revealed that 2,514 (26%) used a catheter at times, with 11% reporting current catheter use and 15% past use only. One-third of men had used a catheter, significantly more than did women (32% vs. 24%, P less than .001). Those who catheterized tended to have a longer history of MS (17.1 vs. 12.1 years, P less than .001); were more disabled, as measured by the PDDS (Patient Determined Disease Steps) scale; and had poorer quality of life, as measured by the SF-12 (Short Form–12 Quality of Life) inventory (P less than .001 in all components), she reported in a poster at the annual meeting of the American Urogynecologic Society.

The preferred method of catheterization differed between men and women. Men tended to prefer indwelling methods such as transurethral Foley catheterization (TFC) (47% males vs. 41% females, P = .003) or suprapubic catheterization (SPC) (12% vs. 6%, respectively, P less than .001). Overall, the most common methods of catheterization were intermittent self-catheterization (81%), followed by TFC (43%) and SPC (8%).

Overactive bladder symptoms, as indicated by a score of greater than 1 on the UDI-6 (Urogenital Distress Inventory), were more severe in those who catheterized (P less than .001). The exception was for severe nocturia, which was more frequent in those who did not catheterize.

Only 44% of the respondents had undergone urologic evaluation, including urodynamic testing (21%) and post-void residual screening (26%). Overall, 37% were prescribed an anticholinergic medication, although this percentage increased to 55% for those who catheterized (compared with 30% of those who did not catheterize, P less than .001). The medications used were generally older anticholinergics such as oxybutynin and tolterodine. A small fraction had undergone sacral neuromodulation (0.3%) or intradetrusor injection with onabotulinumtoxinA (0.9%).

Dr. Mahajan indicated she had no relevant disclosures.