Rheumatoid Arthritis

NEWPORT BEACH, CALIF. – Etanercept and a few other tumor necrosis factor inhibitors should be considered first-line therapy for treating rheumatoid arthritis in patients with active hepatitis C virus infection, according to Dr. Leonard Calabrese, chair of clinical immunology and professor of medicine at the Cleveland Clinic.

A systematic literature review (Rheumatology (Oxford) 2011;50:1700-11) that included 153 patients – 91 with rheumatoid arthritis (RA) – "demonstrated quite clearly that there are no safety signals from this. TNF inhibitors work in the same general manner with the same predicted responses in hepatitis C patients as they do in patients who are uninfected," he said.

"Most of the data are on etanercept," and recent guidelines from the American College of Rheumatology recommend it in RA patients with hepatitis C based on observations and other level-C evidence, he noted.

For those and other reasons, "I consider TNF inhibitors first-lines of therapy. These drugs can [also] be used concomitantly" with hepatitis C treatments, including protease inhibitors, which seem to greatly improve cure rates when included with other antiviral therapies, he said at Perspectives in Rheumatic Diseases 2012, held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"When we find somebody with hepatitis C in our practice, we are doing them a huge favor because we can bring them into the circle of care and treat the thing that is more serious than their" RA, Dr. Calabrese said.

Meanwhile, the guidelines do not recommend methotrexate or leflunomide in the setting of hepatitis C virus infection because the drugs might cause additional liver damage.

Among others, Dr. Calabrese screens baby boomers – the largest reservoir of hepatitis C in the United States – and people going on to high-risk drugs, "which is basically anyone going onto a" disease-modifying antirheumatic drug, he said.

"Having antibody to hepatitis C does not prove you have chronic hepatitis C infection, only that you have immunologic memory to the virus. The confirmatory test [for active infection] is the presence of [hepatitis C virus] RNA in the serum, detected by" polymerase chain reaction. "When you find this, the most important part is to refer [the patient] to a hepatologist," he said.

Screening for hepatitis C based on liver enzymes "is a fallacy," he said. Patients with chronic infection can have normal levels, and persistently normal levels do not rule out significant disease.

Perhaps 5 million people in the United States have active, chronic infection. There’s been a slight uptick in cases among men who have sex with men and drug users in rural areas who inject prescription drugs, he noted.

Dr. Calabrese is a consultant for Aventis, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer. He is a speaker for Amgen. SDEF and this news organization are owned by Frontline Medical Communications.

NEWPORT BEACH, CALIF. – Etanercept and a few other tumor necrosis factor inhibitors should be considered first-line therapy for treating rheumatoid arthritis in patients with active hepatitis C virus infection, according to Dr. Leonard Calabrese, chair of clinical immunology and professor of medicine at the Cleveland Clinic.

A systematic literature review (Rheumatology (Oxford) 2011;50:1700-11) that included 153 patients – 91 with rheumatoid arthritis (RA) – "demonstrated quite clearly that there are no safety signals from this. TNF inhibitors work in the same general manner with the same predicted responses in hepatitis C patients as they do in patients who are uninfected," he said.

"Most of the data are on etanercept," and recent guidelines from the American College of Rheumatology recommend it in RA patients with hepatitis C based on observations and other level-C evidence, he noted.

For those and other reasons, "I consider TNF inhibitors first-lines of therapy. These drugs can [also] be used concomitantly" with hepatitis C treatments, including protease inhibitors, which seem to greatly improve cure rates when included with other antiviral therapies, he said at Perspectives in Rheumatic Diseases 2012, held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"When we find somebody with hepatitis C in our practice, we are doing them a huge favor because we can bring them into the circle of care and treat the thing that is more serious than their" RA, Dr. Calabrese said.

Meanwhile, the guidelines do not recommend methotrexate or leflunomide in the setting of hepatitis C virus infection because the drugs might cause additional liver damage.

Among others, Dr. Calabrese screens baby boomers – the largest reservoir of hepatitis C in the United States – and people going on to high-risk drugs, "which is basically anyone going onto a" disease-modifying antirheumatic drug, he said.

"Having antibody to hepatitis C does not prove you have chronic hepatitis C infection, only that you have immunologic memory to the virus. The confirmatory test [for active infection] is the presence of [hepatitis C virus] RNA in the serum, detected by" polymerase chain reaction. "When you find this, the most important part is to refer [the patient] to a hepatologist," he said.

Screening for hepatitis C based on liver enzymes "is a fallacy," he said. Patients with chronic infection can have normal levels, and persistently normal levels do not rule out significant disease.

Perhaps 5 million people in the United States have active, chronic infection. There’s been a slight uptick in cases among men who have sex with men and drug users in rural areas who inject prescription drugs, he noted.

Dr. Calabrese is a consultant for Aventis, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer. He is a speaker for Amgen. SDEF and this news organization are owned by Frontline Medical Communications.

NEWPORT BEACH, CALIF. – Etanercept and a few other tumor necrosis factor inhibitors should be considered first-line therapy for treating rheumatoid arthritis in patients with active hepatitis C virus infection, according to Dr. Leonard Calabrese, chair of clinical immunology and professor of medicine at the Cleveland Clinic.

A systematic literature review (Rheumatology (Oxford) 2011;50:1700-11) that included 153 patients – 91 with rheumatoid arthritis (RA) – "demonstrated quite clearly that there are no safety signals from this. TNF inhibitors work in the same general manner with the same predicted responses in hepatitis C patients as they do in patients who are uninfected," he said.

"Most of the data are on etanercept," and recent guidelines from the American College of Rheumatology recommend it in RA patients with hepatitis C based on observations and other level-C evidence, he noted.

For those and other reasons, "I consider TNF inhibitors first-lines of therapy. These drugs can [also] be used concomitantly" with hepatitis C treatments, including protease inhibitors, which seem to greatly improve cure rates when included with other antiviral therapies, he said at Perspectives in Rheumatic Diseases 2012, held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"When we find somebody with hepatitis C in our practice, we are doing them a huge favor because we can bring them into the circle of care and treat the thing that is more serious than their" RA, Dr. Calabrese said.

Meanwhile, the guidelines do not recommend methotrexate or leflunomide in the setting of hepatitis C virus infection because the drugs might cause additional liver damage.

Among others, Dr. Calabrese screens baby boomers – the largest reservoir of hepatitis C in the United States – and people going on to high-risk drugs, "which is basically anyone going onto a" disease-modifying antirheumatic drug, he said.

"Having antibody to hepatitis C does not prove you have chronic hepatitis C infection, only that you have immunologic memory to the virus. The confirmatory test [for active infection] is the presence of [hepatitis C virus] RNA in the serum, detected by" polymerase chain reaction. "When you find this, the most important part is to refer [the patient] to a hepatologist," he said.

Screening for hepatitis C based on liver enzymes "is a fallacy," he said. Patients with chronic infection can have normal levels, and persistently normal levels do not rule out significant disease.

Perhaps 5 million people in the United States have active, chronic infection. There’s been a slight uptick in cases among men who have sex with men and drug users in rural areas who inject prescription drugs, he noted.

Dr. Calabrese is a consultant for Aventis, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer. He is a speaker for Amgen. SDEF and this news organization are owned by Frontline Medical Communications.

Low-dose short term oral corticosteroids can be an effective DMARD when used in combination with methotrexate in patients with very early rheumatoid arthritis, according to Dr. Daniel E. Furst, who is the Carl M. Pearson Professor of Medicine in the Division of Rheumatology at the University of California, Los Angeles. At the annual Perspectives in Rheumatic Diseases conference, Dr. Furst also discussed treatment advances in RA. The meeting was held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Low-dose short term oral corticosteroids can be an effective DMARD when used in combination with methotrexate in patients with very early rheumatoid arthritis, according to Dr. Daniel E. Furst, who is the Carl M. Pearson Professor of Medicine in the Division of Rheumatology at the University of California, Los Angeles. At the annual Perspectives in Rheumatic Diseases conference, Dr. Furst also discussed treatment advances in RA. The meeting was held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Low-dose short term oral corticosteroids can be an effective DMARD when used in combination with methotrexate in patients with very early rheumatoid arthritis, according to Dr. Daniel E. Furst, who is the Carl M. Pearson Professor of Medicine in the Division of Rheumatology at the University of California, Los Angeles. At the annual Perspectives in Rheumatic Diseases conference, Dr. Furst also discussed treatment advances in RA. The meeting was held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

There is ample evidence that nonpharmacologic therapies including education, exercises such as yoga, tai chi, and cognitive behavioral therapies can be very effective tools in the management of chronic pain in patients with rheumatic diseases.

However, rheumatologists do not often reach for these tools, at least in part because third party payers do not often reimburse for them, according to Dr. Daniel J. Clauw, Director of the Chronic Pain and Fatigue Research Center at the University of Michigan in Ann Arbor. Dr. Clauw discusses how to choose the best nonpharmacologic therapies for each patient. Hint: Let the patient guide the choice. Dr. Clauw spoke at the annual Perspectives on Rheumatic Diseases,  held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

There is ample evidence that nonpharmacologic therapies including education, exercises such as yoga, tai chi, and cognitive behavioral therapies can be very effective tools in the management of chronic pain in patients with rheumatic diseases.

However, rheumatologists do not often reach for these tools, at least in part because third party payers do not often reimburse for them, according to Dr. Daniel J. Clauw, Director of the Chronic Pain and Fatigue Research Center at the University of Michigan in Ann Arbor. Dr. Clauw discusses how to choose the best nonpharmacologic therapies for each patient. Hint: Let the patient guide the choice. Dr. Clauw spoke at the annual Perspectives on Rheumatic Diseases,  held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

There is ample evidence that nonpharmacologic therapies including education, exercises such as yoga, tai chi, and cognitive behavioral therapies can be very effective tools in the management of chronic pain in patients with rheumatic diseases.

However, rheumatologists do not often reach for these tools, at least in part because third party payers do not often reimburse for them, according to Dr. Daniel J. Clauw, Director of the Chronic Pain and Fatigue Research Center at the University of Michigan in Ann Arbor. Dr. Clauw discusses how to choose the best nonpharmacologic therapies for each patient. Hint: Let the patient guide the choice. Dr. Clauw spoke at the annual Perspectives on Rheumatic Diseases,  held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Reactive arthritis that is due to Chlamydia trachomatis infection responds to antibiotic therapy. Other infectious causes of the condition do not.

So it is worth checking the synovial fluid of affected joints for evidence of chlamydia polymerase chain reaction (PCR), according to Dr. Atul Deodhar, professor of medicine at Oregon Health and Science University in Portland.

In a recent randomized trial, 6 months of rifampin plus either azithromycin or doxycycline significantly improved outcomes versus placebo in patients with chlamydia-induced reactive arthritis. Synovial fluid PCRs were positive for chlamydia in all 42 patients (Arthritis Rheum. 2010;62:1298-307).

The study "has changed my practice. I now send synovial fluid for PCR. I have found several patients" positive for chlamydia, "and we are treating them with antibiotics," Dr. Deodhar said; he also sends urine samples for chlamydia testing.

The primary end point in the study – an improvement of 20% or more in at least four of six variables such as swollen joint count – was achieved by 17 of 27 antibiotic patients (63%) but only 3 of 15 placebo patients (20%). Six patients treated with antibiotics but none of the patients in the placebo group went into complete remission during the trial. Patients on antibiotic were also more likely to clear chlamydia from their joints.

It’s a different story when reactive arthritis is triggered by gastrointestinal pathogens such as salmonella, shigella, campylobacter, and yersinia. In those cases, "avoid antibiotics," Dr. Deodhar said.

He and his colleagues found antibiotic therapy just didn’t help in a population study of 575 likely reactive arthritis cases among 6,379 people with culture-confirmed GI infections. His team confirmed reactive arthritis in 54 of the 82 (66%) subjects they were able to exam. Enthesitis was the most frequent finding; arthritis was less common (Ann. Rheum. Dis. 2008;67:1689-96).

Some patients had been given antibiotics for their GI infections, others not. It "didn’t really make any difference to patients developing or not developing reactive arthritis or the severity of it. [Antibiotics] are not going to prevent people [with dysentery] from developing reactive arthritis," Dr. Deodhar said.

They also found that the presence or absence of human leukocyte antigen B27 did not predict risk. In sporadic reactive arthritis cases, the presence of the antigen is "not actually that important in deciding if someone has or does not have reactive arthritis," he said.

Onset of reactive arthritis comes a few days to a maximum of several weeks following the inducing infection. Asymmetrical mono- or oligoarthritis of the lower extremity is the most common joint finding. Uveitis, dactylitis, and enthesitis are also possible.

Besides antibiotics for chlamydia-induced disease, sulfasalazine and tumor necrosis factor inhibitors may help with difficult cases.

Dr. Deodhar disclosed research and grant support from Abbott, Janssen, and UCB.

Reactive arthritis that is due to Chlamydia trachomatis infection responds to antibiotic therapy. Other infectious causes of the condition do not.

So it is worth checking the synovial fluid of affected joints for evidence of chlamydia polymerase chain reaction (PCR), according to Dr. Atul Deodhar, professor of medicine at Oregon Health and Science University in Portland.

In a recent randomized trial, 6 months of rifampin plus either azithromycin or doxycycline significantly improved outcomes versus placebo in patients with chlamydia-induced reactive arthritis. Synovial fluid PCRs were positive for chlamydia in all 42 patients (Arthritis Rheum. 2010;62:1298-307).

The study "has changed my practice. I now send synovial fluid for PCR. I have found several patients" positive for chlamydia, "and we are treating them with antibiotics," Dr. Deodhar said; he also sends urine samples for chlamydia testing.

The primary end point in the study – an improvement of 20% or more in at least four of six variables such as swollen joint count – was achieved by 17 of 27 antibiotic patients (63%) but only 3 of 15 placebo patients (20%). Six patients treated with antibiotics but none of the patients in the placebo group went into complete remission during the trial. Patients on antibiotic were also more likely to clear chlamydia from their joints.

It’s a different story when reactive arthritis is triggered by gastrointestinal pathogens such as salmonella, shigella, campylobacter, and yersinia. In those cases, "avoid antibiotics," Dr. Deodhar said.

He and his colleagues found antibiotic therapy just didn’t help in a population study of 575 likely reactive arthritis cases among 6,379 people with culture-confirmed GI infections. His team confirmed reactive arthritis in 54 of the 82 (66%) subjects they were able to exam. Enthesitis was the most frequent finding; arthritis was less common (Ann. Rheum. Dis. 2008;67:1689-96).

Some patients had been given antibiotics for their GI infections, others not. It "didn’t really make any difference to patients developing or not developing reactive arthritis or the severity of it. [Antibiotics] are not going to prevent people [with dysentery] from developing reactive arthritis," Dr. Deodhar said.

They also found that the presence or absence of human leukocyte antigen B27 did not predict risk. In sporadic reactive arthritis cases, the presence of the antigen is "not actually that important in deciding if someone has or does not have reactive arthritis," he said.

Onset of reactive arthritis comes a few days to a maximum of several weeks following the inducing infection. Asymmetrical mono- or oligoarthritis of the lower extremity is the most common joint finding. Uveitis, dactylitis, and enthesitis are also possible.

Besides antibiotics for chlamydia-induced disease, sulfasalazine and tumor necrosis factor inhibitors may help with difficult cases.

Dr. Deodhar disclosed research and grant support from Abbott, Janssen, and UCB.

Reactive arthritis that is due to Chlamydia trachomatis infection responds to antibiotic therapy. Other infectious causes of the condition do not.

So it is worth checking the synovial fluid of affected joints for evidence of chlamydia polymerase chain reaction (PCR), according to Dr. Atul Deodhar, professor of medicine at Oregon Health and Science University in Portland.

In a recent randomized trial, 6 months of rifampin plus either azithromycin or doxycycline significantly improved outcomes versus placebo in patients with chlamydia-induced reactive arthritis. Synovial fluid PCRs were positive for chlamydia in all 42 patients (Arthritis Rheum. 2010;62:1298-307).

The study "has changed my practice. I now send synovial fluid for PCR. I have found several patients" positive for chlamydia, "and we are treating them with antibiotics," Dr. Deodhar said; he also sends urine samples for chlamydia testing.

The primary end point in the study – an improvement of 20% or more in at least four of six variables such as swollen joint count – was achieved by 17 of 27 antibiotic patients (63%) but only 3 of 15 placebo patients (20%). Six patients treated with antibiotics but none of the patients in the placebo group went into complete remission during the trial. Patients on antibiotic were also more likely to clear chlamydia from their joints.

It’s a different story when reactive arthritis is triggered by gastrointestinal pathogens such as salmonella, shigella, campylobacter, and yersinia. In those cases, "avoid antibiotics," Dr. Deodhar said.

He and his colleagues found antibiotic therapy just didn’t help in a population study of 575 likely reactive arthritis cases among 6,379 people with culture-confirmed GI infections. His team confirmed reactive arthritis in 54 of the 82 (66%) subjects they were able to exam. Enthesitis was the most frequent finding; arthritis was less common (Ann. Rheum. Dis. 2008;67:1689-96).

Some patients had been given antibiotics for their GI infections, others not. It "didn’t really make any difference to patients developing or not developing reactive arthritis or the severity of it. [Antibiotics] are not going to prevent people [with dysentery] from developing reactive arthritis," Dr. Deodhar said.

They also found that the presence or absence of human leukocyte antigen B27 did not predict risk. In sporadic reactive arthritis cases, the presence of the antigen is "not actually that important in deciding if someone has or does not have reactive arthritis," he said.

Onset of reactive arthritis comes a few days to a maximum of several weeks following the inducing infection. Asymmetrical mono- or oligoarthritis of the lower extremity is the most common joint finding. Uveitis, dactylitis, and enthesitis are also possible.

Besides antibiotics for chlamydia-induced disease, sulfasalazine and tumor necrosis factor inhibitors may help with difficult cases.

Dr. Deodhar disclosed research and grant support from Abbott, Janssen, and UCB.

The Consortium of Rheumatology Researchers of North America (or CORRONA) primarily manages a database, and data analysis, of rheumatic diseases. Dr. Joel Kremer, CORRONA president and CEO, offered an update on the group's work at the 2012 Perspectives of Rheumatic Diseases in Newport Beach, Calif., held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

The Consortium of Rheumatology Researchers of North America (or CORRONA) primarily manages a database, and data analysis, of rheumatic diseases. Dr. Joel Kremer, CORRONA president and CEO, offered an update on the group's work at the 2012 Perspectives of Rheumatic Diseases in Newport Beach, Calif., held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

The Consortium of Rheumatology Researchers of North America (or CORRONA) primarily manages a database, and data analysis, of rheumatic diseases. Dr. Joel Kremer, CORRONA president and CEO, offered an update on the group's work at the 2012 Perspectives of Rheumatic Diseases in Newport Beach, Calif., held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

SAN FRANCISCO – The addition of rifampin to long-term antibiotic regimens significantly lowers the risk for Clostridium difficile–associated colitis in patients being treated for osteoarticular infections.

The retrospective cohort study comprised 393 treatment episodes – 55% of them for infections subsequent to arthroplasty – among patients admitted to a Swiss orthopedic surgery unit from 1996 to 2012. The ribotype 027 was not endemic in the region.

The 42% of patients who were treated with combination therapy that included oral rifampin (600 mg/day) were significantly less like to develop C. difficile colitis despite being on the antibiotics for a median of 63 days (ranging from 20-294 days), Caroline Landelle, Pharm.D., Ph.D. and her associates reported at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Rifampin use was inversely associated with C. difficile colitis, with an adjusted hazard ratio of 0.18, Dr. Landelle reported in a poster presentation.

In general, longer duration of antibiotics treatment was associated with C. difficile colitis, with an adjusted hazard ratio of 1.01, said Dr. Landelle of the University of Geneva.

Factors not associated with colitis risk (either positively or negatively) included the use of antianaerobic antibiotics (in 38% of patients), treatment with intravenous vancomycin (in 45%, for a median of 13 days), age, or sex.

Fourteen patients (4%) developed symptomatic C. difficile colitis after a median of 14 days of antibiotic treatment (ranging from 8-193 days). Of these, six patients were on vancomycin (43%) and two patients were receiving rifampin (14%) prior to development of the colitis, Dr. Landelle reported at the meeting, sponsored by the American Society for Microbiology.

"C. difficile colitis was rare despite long-term antibiotic use among patients with osteoarticular infection. In contrast to intravenous vancomycin, combination antibiotic therapy with oral rifampin might protect against C. difficile–associated colitis," the investigators suggested.

The cohort had a median age of 69 years; 41% was female, and 31% of patients were immunosuppressed.

Of the 401 microorganisms isolated from the osteoarticular infections, 32% were methicillin-sensitive Staphylococcus aureus, 16% were methicillin-resistant S. aureus, 17% each were coagulase-negative Staphylococcus or gram-negative bacilli, and 18% were other organisms.

The investigators hypothesized that combination therapy with rifampin or derivative medications might protect against C. difficile colitis because very few cases have been reported of rifampin-associated pseudomembranous colitis, and patients undergoing treatment with long-term antibiotic combination therapy for osteoarticular infections rarely develop symptomatic C. difficile–associated disease.

Rifaximin and other antibiotics belonging to the macrocyclic family are being investigated as alternative therapies for C. difficile–associated disease, Dr. Landelle said. Some studies have shown high rates of C. difficile resistance to rifampin in Europe, but the rate of resistance at her institution was low. In Switzerland, rifamycin antibiotics have been used for decades, but rifaximin is not licensed for the treatment of hepatic encephalopathy, diarrhea, and traveler’s diarrhea or for prophylaxis in patients undergoing GI surgery, which may explain the low rate of resistance there.

The study excluded patients with prior episodes of C. difficile–associated disease, patients being treated with metronidazole, and patients with septic arthritis.

Dr. Landelle did not provide her financial disclosures.

SAN FRANCISCO – The addition of rifampin to long-term antibiotic regimens significantly lowers the risk for Clostridium difficile–associated colitis in patients being treated for osteoarticular infections.

The retrospective cohort study comprised 393 treatment episodes – 55% of them for infections subsequent to arthroplasty – among patients admitted to a Swiss orthopedic surgery unit from 1996 to 2012. The ribotype 027 was not endemic in the region.

The 42% of patients who were treated with combination therapy that included oral rifampin (600 mg/day) were significantly less like to develop C. difficile colitis despite being on the antibiotics for a median of 63 days (ranging from 20-294 days), Caroline Landelle, Pharm.D., Ph.D. and her associates reported at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Rifampin use was inversely associated with C. difficile colitis, with an adjusted hazard ratio of 0.18, Dr. Landelle reported in a poster presentation.

In general, longer duration of antibiotics treatment was associated with C. difficile colitis, with an adjusted hazard ratio of 1.01, said Dr. Landelle of the University of Geneva.

Factors not associated with colitis risk (either positively or negatively) included the use of antianaerobic antibiotics (in 38% of patients), treatment with intravenous vancomycin (in 45%, for a median of 13 days), age, or sex.

Fourteen patients (4%) developed symptomatic C. difficile colitis after a median of 14 days of antibiotic treatment (ranging from 8-193 days). Of these, six patients were on vancomycin (43%) and two patients were receiving rifampin (14%) prior to development of the colitis, Dr. Landelle reported at the meeting, sponsored by the American Society for Microbiology.

"C. difficile colitis was rare despite long-term antibiotic use among patients with osteoarticular infection. In contrast to intravenous vancomycin, combination antibiotic therapy with oral rifampin might protect against C. difficile–associated colitis," the investigators suggested.

The cohort had a median age of 69 years; 41% was female, and 31% of patients were immunosuppressed.

Of the 401 microorganisms isolated from the osteoarticular infections, 32% were methicillin-sensitive Staphylococcus aureus, 16% were methicillin-resistant S. aureus, 17% each were coagulase-negative Staphylococcus or gram-negative bacilli, and 18% were other organisms.

The investigators hypothesized that combination therapy with rifampin or derivative medications might protect against C. difficile colitis because very few cases have been reported of rifampin-associated pseudomembranous colitis, and patients undergoing treatment with long-term antibiotic combination therapy for osteoarticular infections rarely develop symptomatic C. difficile–associated disease.

Rifaximin and other antibiotics belonging to the macrocyclic family are being investigated as alternative therapies for C. difficile–associated disease, Dr. Landelle said. Some studies have shown high rates of C. difficile resistance to rifampin in Europe, but the rate of resistance at her institution was low. In Switzerland, rifamycin antibiotics have been used for decades, but rifaximin is not licensed for the treatment of hepatic encephalopathy, diarrhea, and traveler’s diarrhea or for prophylaxis in patients undergoing GI surgery, which may explain the low rate of resistance there.

The study excluded patients with prior episodes of C. difficile–associated disease, patients being treated with metronidazole, and patients with septic arthritis.

Dr. Landelle did not provide her financial disclosures.

SAN FRANCISCO – The addition of rifampin to long-term antibiotic regimens significantly lowers the risk for Clostridium difficile–associated colitis in patients being treated for osteoarticular infections.

The retrospective cohort study comprised 393 treatment episodes – 55% of them for infections subsequent to arthroplasty – among patients admitted to a Swiss orthopedic surgery unit from 1996 to 2012. The ribotype 027 was not endemic in the region.

The 42% of patients who were treated with combination therapy that included oral rifampin (600 mg/day) were significantly less like to develop C. difficile colitis despite being on the antibiotics for a median of 63 days (ranging from 20-294 days), Caroline Landelle, Pharm.D., Ph.D. and her associates reported at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Rifampin use was inversely associated with C. difficile colitis, with an adjusted hazard ratio of 0.18, Dr. Landelle reported in a poster presentation.

In general, longer duration of antibiotics treatment was associated with C. difficile colitis, with an adjusted hazard ratio of 1.01, said Dr. Landelle of the University of Geneva.

Factors not associated with colitis risk (either positively or negatively) included the use of antianaerobic antibiotics (in 38% of patients), treatment with intravenous vancomycin (in 45%, for a median of 13 days), age, or sex.

Fourteen patients (4%) developed symptomatic C. difficile colitis after a median of 14 days of antibiotic treatment (ranging from 8-193 days). Of these, six patients were on vancomycin (43%) and two patients were receiving rifampin (14%) prior to development of the colitis, Dr. Landelle reported at the meeting, sponsored by the American Society for Microbiology.

"C. difficile colitis was rare despite long-term antibiotic use among patients with osteoarticular infection. In contrast to intravenous vancomycin, combination antibiotic therapy with oral rifampin might protect against C. difficile–associated colitis," the investigators suggested.

The cohort had a median age of 69 years; 41% was female, and 31% of patients were immunosuppressed.

Of the 401 microorganisms isolated from the osteoarticular infections, 32% were methicillin-sensitive Staphylococcus aureus, 16% were methicillin-resistant S. aureus, 17% each were coagulase-negative Staphylococcus or gram-negative bacilli, and 18% were other organisms.

The investigators hypothesized that combination therapy with rifampin or derivative medications might protect against C. difficile colitis because very few cases have been reported of rifampin-associated pseudomembranous colitis, and patients undergoing treatment with long-term antibiotic combination therapy for osteoarticular infections rarely develop symptomatic C. difficile–associated disease.

Rifaximin and other antibiotics belonging to the macrocyclic family are being investigated as alternative therapies for C. difficile–associated disease, Dr. Landelle said. Some studies have shown high rates of C. difficile resistance to rifampin in Europe, but the rate of resistance at her institution was low. In Switzerland, rifamycin antibiotics have been used for decades, but rifaximin is not licensed for the treatment of hepatic encephalopathy, diarrhea, and traveler’s diarrhea or for prophylaxis in patients undergoing GI surgery, which may explain the low rate of resistance there.

The study excluded patients with prior episodes of C. difficile–associated disease, patients being treated with metronidazole, and patients with septic arthritis.

Dr. Landelle did not provide her financial disclosures.

BOSTON – Patients with psoriasis are almost nine times more likely to have enlarged tonsils, compared with patients without psoriasis, according to the results of a small study.

"Our findings suggest that hypertrophic tonsils may be associated with a pathogenic role in psoriasis," Dr. Marianna Shvartsbeyn and her coinvestigators reported in a poster presented at the American Academy of Dermatology’s Summer Academy Meeting. But it is still too soon to know the clinical implications.

In all, 32 patients with psoriasis and 14 patients with noninflammatory skin conditions (common warts, melanoma, and nonmelanoma skin diseases) were recruited. Patients who previously underwent tonsillectomy were excluded.

Tonsils were examined by one investigator, using a 5-point standardized tonsillar hypertrophy grading scale (adopted from Am. Fam. Physician 2004;69:1147-55).

Tonsils that were entirely within the tonsillar fossa received a grade of 0. Tonsils occupying less than 25% of the lateral dimension of the oropharynx, as measured between the anterior tonsillar pillars, received a grade of 1; tonsils occupying less than 50% of the lateral dimension of the oropharynx were a 2; tonsils occupying less than 75% of the lateral dimension of the oropharynx were a 3; and tonsils occupying 75 % or more of the lateral dimension of the oropharynx received a grade of 4.

Chart reviews were conducted to collect information on patient age, sex, race, social history (tobacco, alcohol, and drug use), diagnosis of skin condition, and the duration/severity of disease, noted Dr. Shvartsbeyn and her colleague of the departments of pathology and dermatology at the New York University.

Patients with psoriasis were found to have had an odds ratio of 8.77 for having enlarged tonsils (grade 2 or greater), compared with healthy controls. Tonsillar size also was significantly larger in patients with psoriasis (mean tonsil grade, 1.78), than in control patients (mean tonsil grade, 0.86); the severity of psoriasis was positively associated with tonsil size, Dr. Shvartsbeyn and her colleagues reported.

Limited clinical data have suggested that there is an association between hypertrophic tonsils and inflammatory skin disease. Small studies have shown that among patients with psoriasis, the cutaneous lesions disappeared or improved after tonsillectomy. It is suspected that there may be a genetic predisposition that makes certain patient populations more susceptible, the researchers noted.

Histopathologic studies also point to the possible link between the robust immune response that takes place in the tonsils and the changes in the skin of patients with pustulosis palmaris et plantaris (PPP).

Histologic evaluation of tonsils obtained from patients with PPP has revealed enlargement of the secondary T nodules and atrophy of the lymph follicles, with a decrease in the number of the germinal center cells and fibrosis – changes typically seen in older tonsils. This finding provides indirect evidence of the intensely advanced stage of the immune response within the tonsils.

"Our hypothesis is that in chronic tonsillar hypertrophy, bacterial species that reside in the tonsils are released into the circulation and cause stimulation of T cells. As a result of this constant chronic stimulation, an autoreactive clone may be formed. The auto-clone may produce an antibody attacking the skin and drive inflammatory response. In some individuals, this exaggerated immune response may manifest as psoriasis," the investigators wrote.

And although there is empirical evidence "that tonsillectomy improved skin lesions in patients with psoriasis and pustulosis palmaris et plantaris in small retrospective studies, further studies are needed. ... The observed association needs validation and interventional study is needed to prove causation/contribution," Dr. Shvartsbeyn noted in an interview.

The study was supported by grants from the National Cancer Institute, the National Institute for Allergy and Infectious Diseases, and the National Institute of Dental and Craniofacial Research. The investigators did not report having any conflicts of interest.

BOSTON – Patients with psoriasis are almost nine times more likely to have enlarged tonsils, compared with patients without psoriasis, according to the results of a small study.

"Our findings suggest that hypertrophic tonsils may be associated with a pathogenic role in psoriasis," Dr. Marianna Shvartsbeyn and her coinvestigators reported in a poster presented at the American Academy of Dermatology’s Summer Academy Meeting. But it is still too soon to know the clinical implications.

In all, 32 patients with psoriasis and 14 patients with noninflammatory skin conditions (common warts, melanoma, and nonmelanoma skin diseases) were recruited. Patients who previously underwent tonsillectomy were excluded.

Tonsils were examined by one investigator, using a 5-point standardized tonsillar hypertrophy grading scale (adopted from Am. Fam. Physician 2004;69:1147-55).

Tonsils that were entirely within the tonsillar fossa received a grade of 0. Tonsils occupying less than 25% of the lateral dimension of the oropharynx, as measured between the anterior tonsillar pillars, received a grade of 1; tonsils occupying less than 50% of the lateral dimension of the oropharynx were a 2; tonsils occupying less than 75% of the lateral dimension of the oropharynx were a 3; and tonsils occupying 75 % or more of the lateral dimension of the oropharynx received a grade of 4.

Chart reviews were conducted to collect information on patient age, sex, race, social history (tobacco, alcohol, and drug use), diagnosis of skin condition, and the duration/severity of disease, noted Dr. Shvartsbeyn and her colleague of the departments of pathology and dermatology at the New York University.

Patients with psoriasis were found to have had an odds ratio of 8.77 for having enlarged tonsils (grade 2 or greater), compared with healthy controls. Tonsillar size also was significantly larger in patients with psoriasis (mean tonsil grade, 1.78), than in control patients (mean tonsil grade, 0.86); the severity of psoriasis was positively associated with tonsil size, Dr. Shvartsbeyn and her colleagues reported.

Limited clinical data have suggested that there is an association between hypertrophic tonsils and inflammatory skin disease. Small studies have shown that among patients with psoriasis, the cutaneous lesions disappeared or improved after tonsillectomy. It is suspected that there may be a genetic predisposition that makes certain patient populations more susceptible, the researchers noted.

Histopathologic studies also point to the possible link between the robust immune response that takes place in the tonsils and the changes in the skin of patients with pustulosis palmaris et plantaris (PPP).

Histologic evaluation of tonsils obtained from patients with PPP has revealed enlargement of the secondary T nodules and atrophy of the lymph follicles, with a decrease in the number of the germinal center cells and fibrosis – changes typically seen in older tonsils. This finding provides indirect evidence of the intensely advanced stage of the immune response within the tonsils.

"Our hypothesis is that in chronic tonsillar hypertrophy, bacterial species that reside in the tonsils are released into the circulation and cause stimulation of T cells. As a result of this constant chronic stimulation, an autoreactive clone may be formed. The auto-clone may produce an antibody attacking the skin and drive inflammatory response. In some individuals, this exaggerated immune response may manifest as psoriasis," the investigators wrote.

And although there is empirical evidence "that tonsillectomy improved skin lesions in patients with psoriasis and pustulosis palmaris et plantaris in small retrospective studies, further studies are needed. ... The observed association needs validation and interventional study is needed to prove causation/contribution," Dr. Shvartsbeyn noted in an interview.

The study was supported by grants from the National Cancer Institute, the National Institute for Allergy and Infectious Diseases, and the National Institute of Dental and Craniofacial Research. The investigators did not report having any conflicts of interest.

BOSTON – Patients with psoriasis are almost nine times more likely to have enlarged tonsils, compared with patients without psoriasis, according to the results of a small study.

"Our findings suggest that hypertrophic tonsils may be associated with a pathogenic role in psoriasis," Dr. Marianna Shvartsbeyn and her coinvestigators reported in a poster presented at the American Academy of Dermatology’s Summer Academy Meeting. But it is still too soon to know the clinical implications.

In all, 32 patients with psoriasis and 14 patients with noninflammatory skin conditions (common warts, melanoma, and nonmelanoma skin diseases) were recruited. Patients who previously underwent tonsillectomy were excluded.

Tonsils were examined by one investigator, using a 5-point standardized tonsillar hypertrophy grading scale (adopted from Am. Fam. Physician 2004;69:1147-55).

Tonsils that were entirely within the tonsillar fossa received a grade of 0. Tonsils occupying less than 25% of the lateral dimension of the oropharynx, as measured between the anterior tonsillar pillars, received a grade of 1; tonsils occupying less than 50% of the lateral dimension of the oropharynx were a 2; tonsils occupying less than 75% of the lateral dimension of the oropharynx were a 3; and tonsils occupying 75 % or more of the lateral dimension of the oropharynx received a grade of 4.

Chart reviews were conducted to collect information on patient age, sex, race, social history (tobacco, alcohol, and drug use), diagnosis of skin condition, and the duration/severity of disease, noted Dr. Shvartsbeyn and her colleague of the departments of pathology and dermatology at the New York University.

Patients with psoriasis were found to have had an odds ratio of 8.77 for having enlarged tonsils (grade 2 or greater), compared with healthy controls. Tonsillar size also was significantly larger in patients with psoriasis (mean tonsil grade, 1.78), than in control patients (mean tonsil grade, 0.86); the severity of psoriasis was positively associated with tonsil size, Dr. Shvartsbeyn and her colleagues reported.

Limited clinical data have suggested that there is an association between hypertrophic tonsils and inflammatory skin disease. Small studies have shown that among patients with psoriasis, the cutaneous lesions disappeared or improved after tonsillectomy. It is suspected that there may be a genetic predisposition that makes certain patient populations more susceptible, the researchers noted.

Histopathologic studies also point to the possible link between the robust immune response that takes place in the tonsils and the changes in the skin of patients with pustulosis palmaris et plantaris (PPP).

Histologic evaluation of tonsils obtained from patients with PPP has revealed enlargement of the secondary T nodules and atrophy of the lymph follicles, with a decrease in the number of the germinal center cells and fibrosis – changes typically seen in older tonsils. This finding provides indirect evidence of the intensely advanced stage of the immune response within the tonsils.

"Our hypothesis is that in chronic tonsillar hypertrophy, bacterial species that reside in the tonsils are released into the circulation and cause stimulation of T cells. As a result of this constant chronic stimulation, an autoreactive clone may be formed. The auto-clone may produce an antibody attacking the skin and drive inflammatory response. In some individuals, this exaggerated immune response may manifest as psoriasis," the investigators wrote.

And although there is empirical evidence "that tonsillectomy improved skin lesions in patients with psoriasis and pustulosis palmaris et plantaris in small retrospective studies, further studies are needed. ... The observed association needs validation and interventional study is needed to prove causation/contribution," Dr. Shvartsbeyn noted in an interview.

The study was supported by grants from the National Cancer Institute, the National Institute for Allergy and Infectious Diseases, and the National Institute of Dental and Craniofacial Research. The investigators did not report having any conflicts of interest.

Evidence continues to accumulate that the potent anti-inflammatory effect of drugs that block tumor necrosis factor can significantly dampen cardiovascular-disease risk in patients with rheumatoid arthritis, even though definitive proof from a prospective trial is still lacking.

Two recent pieces of suggestive evidence came from a meta-analysis of four placebo-controlled trials of adalimumab (Humira) that together included nearly 2,500 patients with rheumatoid arthritis, and from two prospective cohort studies of 828 RA patients that compared the outcomes of those treated with either adalimumab or etanercept (Enbrel) to the outcomes of similar patients who did not receive an anti–tumor necrosis factor drug.

In both studies, treatment with an anti-TNF agent was linked to a statistically significant cut in cardiovascular (CV) events of about 50%.

These results support another recent, similar finding reported in June at the Annual European Congress of Rheumatology in London. In that study, analysis of medical records from more than 109,000 U.S. patients with RA showed that every 6 months of treatment with an anti-TNF drug reduced the rate of CV events by 13%, compared with RA patients who did not receive a TNF blocker.

The meta-analysis of four trials included data collected in the ARMADA (Arthritis Rheum. 2003;48:35-45), DEO19 (Arthritis Rheum. 2004;50:1400-11), PREMIER (Arthritis Rheum. 2006;54:26-37), and OPTIMA (Ann. Rheum. Dis. 2012 May [doi: 10.1136/annrheumdis-2011-201247]) trials. Collectively, these four studies included 1,411 RA patients treated with both adalimumab and methotrexate, and 1,036 patients who received methotrexate but no anti-TNF drug. At baseline, patients in these two treatment groups had similar demographic and CV disease risk profiles.

Mitchel L. Zoler/IMNG Medical Media

During study periods that ranged from 16 to 104 weeks, the incidence of major adverse CV events was 1.3% in patients who received adalimumab, and 2% in those who didn’t. This difference represents a statistically significant, 2/3 drop in the risk for a major CV event in a proportional-hazard model, said Dr. Gerd Burmester, lead investigator for the analysis and a rheumatologist and professor of medicine at Charité Hospital in Berlin. His analysis also showed a statistically significant risk reduction with adalimumab in the rate of nonfatal myocardial infarction, but no significant effect of adalimumab on the rates of nonfatal myocardial infarction or nonfatal stroke compared with patients not receiving adalimumab.

A limitation of the analysis was that none of the four trials was powered to assess CV outcomes, Dr. Burmester said.

The second study used data collected from two cohorts: the CARRÉ (Cardiovascular Research and Rheumatoid Arthritis) study, a prospective Dutch cohort study of 309 randomly selected RA patients who were not treated with a TNF blocker; and the Biologics cohort, which involves 519 Dutch RA patients who have been followed since they began treatment with an anti-TNF drug for the first time, either adalimumab or etanercept.

During follow-up, there were 8 CV events per 1,000 patient-years in the cohort receiving an anti-TNF drug, compared with 23 events per 1,000 patient-years in patients not on an anti-TNF agent, a statistically significant reduction. In a proportional hazards model that adjusted for baseline differences in age and gender, treatment with an anti-TNF agent reduced the rate of CV events by about half, a statistically significant effect, said Dr. Alper M. van Sijl, a researcher at the Reade Centre for Rehabilitation and Rheumatology at the VU Medical Center in Amsterdam.

"Our observations confirm the association between strong suppression of inflammation [with an anti-TNF drug] and curbing the cardiovascular risk in RA," said Dr. van Sijl and his colleagues. But they cautioned that because of the design of the study it remains unclear whether this was a real effect of the anti-TNF drugs, or a bias to treat patients with lower CV disease risk with a TNF blocker.

Dr. Burmester said that he has been a consultant to, served as a speaker for, and received research support from Abbott, the company that markets adalimumab. Dr. van Silj said that he had no disclosures.

Evidence continues to accumulate that the potent anti-inflammatory effect of drugs that block tumor necrosis factor can significantly dampen cardiovascular-disease risk in patients with rheumatoid arthritis, even though definitive proof from a prospective trial is still lacking.

Two recent pieces of suggestive evidence came from a meta-analysis of four placebo-controlled trials of adalimumab (Humira) that together included nearly 2,500 patients with rheumatoid arthritis, and from two prospective cohort studies of 828 RA patients that compared the outcomes of those treated with either adalimumab or etanercept (Enbrel) to the outcomes of similar patients who did not receive an anti–tumor necrosis factor drug.

In both studies, treatment with an anti-TNF agent was linked to a statistically significant cut in cardiovascular (CV) events of about 50%.

These results support another recent, similar finding reported in June at the Annual European Congress of Rheumatology in London. In that study, analysis of medical records from more than 109,000 U.S. patients with RA showed that every 6 months of treatment with an anti-TNF drug reduced the rate of CV events by 13%, compared with RA patients who did not receive a TNF blocker.

The meta-analysis of four trials included data collected in the ARMADA (Arthritis Rheum. 2003;48:35-45), DEO19 (Arthritis Rheum. 2004;50:1400-11), PREMIER (Arthritis Rheum. 2006;54:26-37), and OPTIMA (Ann. Rheum. Dis. 2012 May [doi: 10.1136/annrheumdis-2011-201247]) trials. Collectively, these four studies included 1,411 RA patients treated with both adalimumab and methotrexate, and 1,036 patients who received methotrexate but no anti-TNF drug. At baseline, patients in these two treatment groups had similar demographic and CV disease risk profiles.

Mitchel L. Zoler/IMNG Medical Media

During study periods that ranged from 16 to 104 weeks, the incidence of major adverse CV events was 1.3% in patients who received adalimumab, and 2% in those who didn’t. This difference represents a statistically significant, 2/3 drop in the risk for a major CV event in a proportional-hazard model, said Dr. Gerd Burmester, lead investigator for the analysis and a rheumatologist and professor of medicine at Charité Hospital in Berlin. His analysis also showed a statistically significant risk reduction with adalimumab in the rate of nonfatal myocardial infarction, but no significant effect of adalimumab on the rates of nonfatal myocardial infarction or nonfatal stroke compared with patients not receiving adalimumab.

A limitation of the analysis was that none of the four trials was powered to assess CV outcomes, Dr. Burmester said.

The second study used data collected from two cohorts: the CARRÉ (Cardiovascular Research and Rheumatoid Arthritis) study, a prospective Dutch cohort study of 309 randomly selected RA patients who were not treated with a TNF blocker; and the Biologics cohort, which involves 519 Dutch RA patients who have been followed since they began treatment with an anti-TNF drug for the first time, either adalimumab or etanercept.

During follow-up, there were 8 CV events per 1,000 patient-years in the cohort receiving an anti-TNF drug, compared with 23 events per 1,000 patient-years in patients not on an anti-TNF agent, a statistically significant reduction. In a proportional hazards model that adjusted for baseline differences in age and gender, treatment with an anti-TNF agent reduced the rate of CV events by about half, a statistically significant effect, said Dr. Alper M. van Sijl, a researcher at the Reade Centre for Rehabilitation and Rheumatology at the VU Medical Center in Amsterdam.

"Our observations confirm the association between strong suppression of inflammation [with an anti-TNF drug] and curbing the cardiovascular risk in RA," said Dr. van Sijl and his colleagues. But they cautioned that because of the design of the study it remains unclear whether this was a real effect of the anti-TNF drugs, or a bias to treat patients with lower CV disease risk with a TNF blocker.

Dr. Burmester said that he has been a consultant to, served as a speaker for, and received research support from Abbott, the company that markets adalimumab. Dr. van Silj said that he had no disclosures.

Evidence continues to accumulate that the potent anti-inflammatory effect of drugs that block tumor necrosis factor can significantly dampen cardiovascular-disease risk in patients with rheumatoid arthritis, even though definitive proof from a prospective trial is still lacking.

Two recent pieces of suggestive evidence came from a meta-analysis of four placebo-controlled trials of adalimumab (Humira) that together included nearly 2,500 patients with rheumatoid arthritis, and from two prospective cohort studies of 828 RA patients that compared the outcomes of those treated with either adalimumab or etanercept (Enbrel) to the outcomes of similar patients who did not receive an anti–tumor necrosis factor drug.

In both studies, treatment with an anti-TNF agent was linked to a statistically significant cut in cardiovascular (CV) events of about 50%.

These results support another recent, similar finding reported in June at the Annual European Congress of Rheumatology in London. In that study, analysis of medical records from more than 109,000 U.S. patients with RA showed that every 6 months of treatment with an anti-TNF drug reduced the rate of CV events by 13%, compared with RA patients who did not receive a TNF blocker.

The meta-analysis of four trials included data collected in the ARMADA (Arthritis Rheum. 2003;48:35-45), DEO19 (Arthritis Rheum. 2004;50:1400-11), PREMIER (Arthritis Rheum. 2006;54:26-37), and OPTIMA (Ann. Rheum. Dis. 2012 May [doi: 10.1136/annrheumdis-2011-201247]) trials. Collectively, these four studies included 1,411 RA patients treated with both adalimumab and methotrexate, and 1,036 patients who received methotrexate but no anti-TNF drug. At baseline, patients in these two treatment groups had similar demographic and CV disease risk profiles.

Mitchel L. Zoler/IMNG Medical Media

During study periods that ranged from 16 to 104 weeks, the incidence of major adverse CV events was 1.3% in patients who received adalimumab, and 2% in those who didn’t. This difference represents a statistically significant, 2/3 drop in the risk for a major CV event in a proportional-hazard model, said Dr. Gerd Burmester, lead investigator for the analysis and a rheumatologist and professor of medicine at Charité Hospital in Berlin. His analysis also showed a statistically significant risk reduction with adalimumab in the rate of nonfatal myocardial infarction, but no significant effect of adalimumab on the rates of nonfatal myocardial infarction or nonfatal stroke compared with patients not receiving adalimumab.

A limitation of the analysis was that none of the four trials was powered to assess CV outcomes, Dr. Burmester said.

The second study used data collected from two cohorts: the CARRÉ (Cardiovascular Research and Rheumatoid Arthritis) study, a prospective Dutch cohort study of 309 randomly selected RA patients who were not treated with a TNF blocker; and the Biologics cohort, which involves 519 Dutch RA patients who have been followed since they began treatment with an anti-TNF drug for the first time, either adalimumab or etanercept.

During follow-up, there were 8 CV events per 1,000 patient-years in the cohort receiving an anti-TNF drug, compared with 23 events per 1,000 patient-years in patients not on an anti-TNF agent, a statistically significant reduction. In a proportional hazards model that adjusted for baseline differences in age and gender, treatment with an anti-TNF agent reduced the rate of CV events by about half, a statistically significant effect, said Dr. Alper M. van Sijl, a researcher at the Reade Centre for Rehabilitation and Rheumatology at the VU Medical Center in Amsterdam.

"Our observations confirm the association between strong suppression of inflammation [with an anti-TNF drug] and curbing the cardiovascular risk in RA," said Dr. van Sijl and his colleagues. But they cautioned that because of the design of the study it remains unclear whether this was a real effect of the anti-TNF drugs, or a bias to treat patients with lower CV disease risk with a TNF blocker.

Dr. Burmester said that he has been a consultant to, served as a speaker for, and received research support from Abbott, the company that markets adalimumab. Dr. van Silj said that he had no disclosures.

The use of biologic agents to treat rheumatoid arthritis doesn’t appear to be associated with an increased risk of malignancy, compared with either placebo or with other disease-modifying drugs, according to a report in the Sept. 5 issue of JAMA.

In a meta-analysis of 63 randomized clinical trials of at least 24 weeks’ duration involving 29,423 adults with RA, there was no increase in the risk of cancer in general or in the risk of specific cancers. "Additional systematic reviews of observational studies are needed to establish risk in the longer term," said Dr. Maria A. Lopez-Olivo of the University of Texas M.D. Anderson Cancer Center, Houston, and her associates.

They described their study as the first systematic review and meta-analysis to assess the risk of any type of malignancy solely in RA patients who were taking any of the nine biologic agents approved for such use: abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, or tocilizumab.

There has been concern that these agents could raise cancer risk because they interfere with the immune system. Some data have implicated tumor necrosis factor (TNF) inhibitors in particular, prompting the Food and Drug Administration to recommend adding a warning label citing an excess of cases of spontaneous lymphoma among children and adolescents taking TNF inhibitors.

"While trials in RA are relatively short and cannot evaluate the risk over longer-term exposure as observational studies do, we thought there was a need to conduct an updated meta-analysis of RCTs [randomized controlled trials] because of the older reports of the possible increase in malignancies and the more recent FDA advisory for TNF inhibitors, mostly based on studies in children," the researchers noted.

In the RCTs included in this meta-analysis, sample sizes ranged from 20 to 1,399 subjects. Most study subjects (79%) were white, and 76% were women. The mean duration of RA ranged from less than 1 year to 13 years.

Pharmaceutical companies sponsored 56 of the 63 trials, and another 3 did not disclose their funding sources. The remaining four trials were funded by national organizations, but the agents they used were provided free of charge by manufacturers. "There is evidence that industry-sponsored trials may overestimate the treatment effect and could possibly also overestimate safety," acacording to Dr. Lopez-Olivo and her associates.

A total of 15,989 study subjects were assigned to take biologic agents plus methotrexate and/or other disease-modifying antirheumatic drugs, while 3,615 were assigned to take the biologic agents alone and 9,819 served as control subjects who were given placebos.

A total of 211 malignancies developed during the trials, in 0.77% of the combination-therapy group, 0.64% of the monotherapy group, and 0.66% of the control group. These differences were not significant, the investigators said (JAMA 2012;308:898-908).

Skin cancers accounted for 48 of the malignancies (which included 4 melanomas), 14 were lymphomas, 26 were not specified, and 5 were hematologic nonlymphomas. The remaining 118 malignancies were solid tumors affecting a wide variety of organs including the adrenal glands, bladder, breast, GI system, liver, lung, ovary, pancreas, prostate, kidney, testes, thyroid, tongue, and uterus.

Thus there was no pattern involving a specific type of cancer.

Similarly, there was no pattern involving any of the individual biologic agents, Dr. Lopez-Olivo and her associates said.

"The only increased risk of malignancy we observed was in patients with RA treated with TNF inhibitors plus methotrexate at 52 weeks, for all cancers combined." However, this effect was not consistent across the three separate analytical methods the researchers used, did not occur in patients taking TNF inhibitors as monotherapy, and did not occur at any of the other three time points assessed.

The study findings "suggest that biologic, disease-modifying agents may be generally safe with respect to risk of malignancy in the short term," but their safety in RA patients who have concomitant cancer or risk factors for cancer remains unknown, the researchers said.

No sponsors were involved with this study, and no financial conflicts of interest were reported.

The use of biologic agents to treat rheumatoid arthritis doesn’t appear to be associated with an increased risk of malignancy, compared with either placebo or with other disease-modifying drugs, according to a report in the Sept. 5 issue of JAMA.

In a meta-analysis of 63 randomized clinical trials of at least 24 weeks’ duration involving 29,423 adults with RA, there was no increase in the risk of cancer in general or in the risk of specific cancers. "Additional systematic reviews of observational studies are needed to establish risk in the longer term," said Dr. Maria A. Lopez-Olivo of the University of Texas M.D. Anderson Cancer Center, Houston, and her associates.

They described their study as the first systematic review and meta-analysis to assess the risk of any type of malignancy solely in RA patients who were taking any of the nine biologic agents approved for such use: abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, or tocilizumab.

There has been concern that these agents could raise cancer risk because they interfere with the immune system. Some data have implicated tumor necrosis factor (TNF) inhibitors in particular, prompting the Food and Drug Administration to recommend adding a warning label citing an excess of cases of spontaneous lymphoma among children and adolescents taking TNF inhibitors.

"While trials in RA are relatively short and cannot evaluate the risk over longer-term exposure as observational studies do, we thought there was a need to conduct an updated meta-analysis of RCTs [randomized controlled trials] because of the older reports of the possible increase in malignancies and the more recent FDA advisory for TNF inhibitors, mostly based on studies in children," the researchers noted.

In the RCTs included in this meta-analysis, sample sizes ranged from 20 to 1,399 subjects. Most study subjects (79%) were white, and 76% were women. The mean duration of RA ranged from less than 1 year to 13 years.

Pharmaceutical companies sponsored 56 of the 63 trials, and another 3 did not disclose their funding sources. The remaining four trials were funded by national organizations, but the agents they used were provided free of charge by manufacturers. "There is evidence that industry-sponsored trials may overestimate the treatment effect and could possibly also overestimate safety," acacording to Dr. Lopez-Olivo and her associates.

A total of 15,989 study subjects were assigned to take biologic agents plus methotrexate and/or other disease-modifying antirheumatic drugs, while 3,615 were assigned to take the biologic agents alone and 9,819 served as control subjects who were given placebos.

A total of 211 malignancies developed during the trials, in 0.77% of the combination-therapy group, 0.64% of the monotherapy group, and 0.66% of the control group. These differences were not significant, the investigators said (JAMA 2012;308:898-908).

Skin cancers accounted for 48 of the malignancies (which included 4 melanomas), 14 were lymphomas, 26 were not specified, and 5 were hematologic nonlymphomas. The remaining 118 malignancies were solid tumors affecting a wide variety of organs including the adrenal glands, bladder, breast, GI system, liver, lung, ovary, pancreas, prostate, kidney, testes, thyroid, tongue, and uterus.

Thus there was no pattern involving a specific type of cancer.

Similarly, there was no pattern involving any of the individual biologic agents, Dr. Lopez-Olivo and her associates said.

"The only increased risk of malignancy we observed was in patients with RA treated with TNF inhibitors plus methotrexate at 52 weeks, for all cancers combined." However, this effect was not consistent across the three separate analytical methods the researchers used, did not occur in patients taking TNF inhibitors as monotherapy, and did not occur at any of the other three time points assessed.

The study findings "suggest that biologic, disease-modifying agents may be generally safe with respect to risk of malignancy in the short term," but their safety in RA patients who have concomitant cancer or risk factors for cancer remains unknown, the researchers said.

No sponsors were involved with this study, and no financial conflicts of interest were reported.

The use of biologic agents to treat rheumatoid arthritis doesn’t appear to be associated with an increased risk of malignancy, compared with either placebo or with other disease-modifying drugs, according to a report in the Sept. 5 issue of JAMA.

In a meta-analysis of 63 randomized clinical trials of at least 24 weeks’ duration involving 29,423 adults with RA, there was no increase in the risk of cancer in general or in the risk of specific cancers. "Additional systematic reviews of observational studies are needed to establish risk in the longer term," said Dr. Maria A. Lopez-Olivo of the University of Texas M.D. Anderson Cancer Center, Houston, and her associates.

They described their study as the first systematic review and meta-analysis to assess the risk of any type of malignancy solely in RA patients who were taking any of the nine biologic agents approved for such use: abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, or tocilizumab.

There has been concern that these agents could raise cancer risk because they interfere with the immune system. Some data have implicated tumor necrosis factor (TNF) inhibitors in particular, prompting the Food and Drug Administration to recommend adding a warning label citing an excess of cases of spontaneous lymphoma among children and adolescents taking TNF inhibitors.

"While trials in RA are relatively short and cannot evaluate the risk over longer-term exposure as observational studies do, we thought there was a need to conduct an updated meta-analysis of RCTs [randomized controlled trials] because of the older reports of the possible increase in malignancies and the more recent FDA advisory for TNF inhibitors, mostly based on studies in children," the researchers noted.

In the RCTs included in this meta-analysis, sample sizes ranged from 20 to 1,399 subjects. Most study subjects (79%) were white, and 76% were women. The mean duration of RA ranged from less than 1 year to 13 years.

Pharmaceutical companies sponsored 56 of the 63 trials, and another 3 did not disclose their funding sources. The remaining four trials were funded by national organizations, but the agents they used were provided free of charge by manufacturers. "There is evidence that industry-sponsored trials may overestimate the treatment effect and could possibly also overestimate safety," acacording to Dr. Lopez-Olivo and her associates.

A total of 15,989 study subjects were assigned to take biologic agents plus methotrexate and/or other disease-modifying antirheumatic drugs, while 3,615 were assigned to take the biologic agents alone and 9,819 served as control subjects who were given placebos.

A total of 211 malignancies developed during the trials, in 0.77% of the combination-therapy group, 0.64% of the monotherapy group, and 0.66% of the control group. These differences were not significant, the investigators said (JAMA 2012;308:898-908).

Skin cancers accounted for 48 of the malignancies (which included 4 melanomas), 14 were lymphomas, 26 were not specified, and 5 were hematologic nonlymphomas. The remaining 118 malignancies were solid tumors affecting a wide variety of organs including the adrenal glands, bladder, breast, GI system, liver, lung, ovary, pancreas, prostate, kidney, testes, thyroid, tongue, and uterus.

Thus there was no pattern involving a specific type of cancer.

Similarly, there was no pattern involving any of the individual biologic agents, Dr. Lopez-Olivo and her associates said.

"The only increased risk of malignancy we observed was in patients with RA treated with TNF inhibitors plus methotrexate at 52 weeks, for all cancers combined." However, this effect was not consistent across the three separate analytical methods the researchers used, did not occur in patients taking TNF inhibitors as monotherapy, and did not occur at any of the other three time points assessed.

The study findings "suggest that biologic, disease-modifying agents may be generally safe with respect to risk of malignancy in the short term," but their safety in RA patients who have concomitant cancer or risk factors for cancer remains unknown, the researchers said.

No sponsors were involved with this study, and no financial conflicts of interest were reported.

ESTES PARK, COLO. – Adding liothyronine is a reasonable treatment strategy when symptoms of hypothyroidism persist on optimal levothyroxine alone, according to Dr. Michael T. McDermott, professor of medicine and clinical pharmacology and director of endocrinology and diabetes practice at the University of Colorado Hospital, Aurora.

Combination levothyroxine/liothyronine (LT4/LT3) therapy is supported by a biologically plausible mechanism of benefit in symptomatic patients who are biochemically euthyroid on LT4. But it’s a step that belongs near the bottom of the management plan for the difficult hypothyroid patient. It should be considered only after other actions have been taken, including a search for coexisting autoimmune conditions or other medical illnesses, Dr. McDermott said at an update on internal medicine sponsored by the University of Colorado.

Every physician who treats hypothyroidism has patients who experience lingering fatigue, memory problems, and other symptoms even though their on-treatment TSH is in the target range of 0.5-2.0 mU/L. Five published studies underscore just how common this situation is. Dr. McDermott cited as an example a study of 397 hypothyroid patients with a TSH in the goal range; 34% scored in the abnormal range on the short-form General Health Questionnaire and 49% had elevated scores on a thyroid symptom-specific questionnaire (Clin. Endocrinol. [Oxf.] 2002;57:577-85).

These are patients who require further general medical evaluation. Their symptoms may be due to a coexistent autoimmune disease. After all, autoimmune diseases tend to cluster. Indeed, when British investigators did a systematic work-up of 495 patients with Hashimoto’s thyroiditis, they found a 14% prevalence of another autoimmune disease. Leading the way was rheumatoid arthritis, present in 4% of subjects. The Hashimoto’s thyroiditis group also had greater than 10-fold increased relative risks of celiac disease, vitiligo, SLE, and Addison’s disease (Am. J. Med. 2010;183:e1-9).

Alternatively, the patient’s lingering symptoms may be due in part to Hashimoto’s thyroiditis itself rather than to hypothyroidism per se. A study of 426 euthyroid women with goiter undergoing thyroidectomy showed that those with antithyroperoxidase antibodies had higher levels of fatigue, nervousness, and irritability, and lower quality of life (Thyroid 2011;21:161-7).

Dr. McDermott routinely obtains a serum 25 vitamin D measurement in his difficult cases of hypothyroidism, since low vitamin D levels are a common cause of fatigue. He also encourages patients with lingering symptoms to eat a well-balanced diet and get regular exercise and sleep, and he refers them for treatment of depression when indicated.

Only after doing all that, does he consider adding LT3. Combined LT4/LT3 therapy is controversial. The first-ever randomized controlled clinical trial was positive (N. Engl. J. Med. 1999;340:424-9), but it was followed by a spate of negative studies. Some physicians closed the book on this treatment strategy after a meta-analysis of all 11 randomized trials showed combination therapy was without benefit (J. Clin. Endocrinol. Metab. 2006; 91: 2,592-9).

However, more recent work has shown that a relatively common polymorphism of the deiodinase 2 gene known as Thr92Ala may predict less responsiveness of psychological symptoms of hypothyroidism to optimal LT4 monotherapy. Deiodinase 2 is responsible for maintaining brain T3 levels, and there is evidence to indicate that the Thr92Ala polymorphism subtly impairs T4 to T3 conversion in the brain.

In a secondary analysis of a study involving 552 hypothyroid patients randomized to LT4 or LT4/LT3, the prevalence of Thr92Ala homozygosity was 16%, and psychological well being in patients with the deiodinase 2 polymorphism improved significantly more on combination therapy than with LT4 alone (J. Clin. Endocrinol. Metab. 2009;94:1623-9).

The fact that the Thr92Ala polymorphism is present in only 16% of individuals on thyroid hormone therapy might explain why so many randomized trials of LT4 versus combination therapy were negative: With study populations of only 20-141 patients, the trials would have been underpowered to detect a significant difference in treatment effect. Unfortunately, genetic testing for deiodinase polymorphisms is not commercially available, the endocrinologist observed.

When he does resort to combination therapy, Dr. McDermott prescribes it in an LT4:LT3 ratio of 10-14:1 to mimic normal thyroid secretion. He generally has patients take LT3 twice daily, with the second dose no later than about 6 p.m. so it doesn’t interfere with sleep. Once-daily slow-release formulations of LT3 are available in Europe and work very well. Several companies are interested in developing a slow-release LT3 for the United States, which would be a welcome development, according to Dr. McDermott.

Another option, once all else has been tried and failed, is to switch to another brand of LT4, he continued. Some patients may have adverse reactions to the various dyes and fillers contained in LT4 pills. When this is a potential concern, levothyroxine sodium (Tirosint), approved by the Food and Drug Administration a couple of years ago, is an attractive option. The LT4 in Tirosint is contained in oil in a liquid gelcap with no dyes or fillers, differentiating it from all other brand name and generic products, Dr. McDermott noted.

He emphasized the importance of avoiding overtreatment with LT4 in an attempt to improve quality of life in patients with residual symptoms despite a TSH of 0.5-2.0 mU/L. Subclinical hyperthyroidism as defined by a TSH below 0.1 mU/L has been shown to significantly increase the risk of hip and spine fractures, atrial fibrillation, and cardiovascular mortality.

Dr. McDermott reported having no financial conflicts.

ESTES PARK, COLO. – Adding liothyronine is a reasonable treatment strategy when symptoms of hypothyroidism persist on optimal levothyroxine alone, according to Dr. Michael T. McDermott, professor of medicine and clinical pharmacology and director of endocrinology and diabetes practice at the University of Colorado Hospital, Aurora.

Combination levothyroxine/liothyronine (LT4/LT3) therapy is supported by a biologically plausible mechanism of benefit in symptomatic patients who are biochemically euthyroid on LT4. But it’s a step that belongs near the bottom of the management plan for the difficult hypothyroid patient. It should be considered only after other actions have been taken, including a search for coexisting autoimmune conditions or other medical illnesses, Dr. McDermott said at an update on internal medicine sponsored by the University of Colorado.

Every physician who treats hypothyroidism has patients who experience lingering fatigue, memory problems, and other symptoms even though their on-treatment TSH is in the target range of 0.5-2.0 mU/L. Five published studies underscore just how common this situation is. Dr. McDermott cited as an example a study of 397 hypothyroid patients with a TSH in the goal range; 34% scored in the abnormal range on the short-form General Health Questionnaire and 49% had elevated scores on a thyroid symptom-specific questionnaire (Clin. Endocrinol. [Oxf.] 2002;57:577-85).

These are patients who require further general medical evaluation. Their symptoms may be due to a coexistent autoimmune disease. After all, autoimmune diseases tend to cluster. Indeed, when British investigators did a systematic work-up of 495 patients with Hashimoto’s thyroiditis, they found a 14% prevalence of another autoimmune disease. Leading the way was rheumatoid arthritis, present in 4% of subjects. The Hashimoto’s thyroiditis group also had greater than 10-fold increased relative risks of celiac disease, vitiligo, SLE, and Addison’s disease (Am. J. Med. 2010;183:e1-9).

Alternatively, the patient’s lingering symptoms may be due in part to Hashimoto’s thyroiditis itself rather than to hypothyroidism per se. A study of 426 euthyroid women with goiter undergoing thyroidectomy showed that those with antithyroperoxidase antibodies had higher levels of fatigue, nervousness, and irritability, and lower quality of life (Thyroid 2011;21:161-7).

Dr. McDermott routinely obtains a serum 25 vitamin D measurement in his difficult cases of hypothyroidism, since low vitamin D levels are a common cause of fatigue. He also encourages patients with lingering symptoms to eat a well-balanced diet and get regular exercise and sleep, and he refers them for treatment of depression when indicated.

Only after doing all that, does he consider adding LT3. Combined LT4/LT3 therapy is controversial. The first-ever randomized controlled clinical trial was positive (N. Engl. J. Med. 1999;340:424-9), but it was followed by a spate of negative studies. Some physicians closed the book on this treatment strategy after a meta-analysis of all 11 randomized trials showed combination therapy was without benefit (J. Clin. Endocrinol. Metab. 2006; 91: 2,592-9).

However, more recent work has shown that a relatively common polymorphism of the deiodinase 2 gene known as Thr92Ala may predict less responsiveness of psychological symptoms of hypothyroidism to optimal LT4 monotherapy. Deiodinase 2 is responsible for maintaining brain T3 levels, and there is evidence to indicate that the Thr92Ala polymorphism subtly impairs T4 to T3 conversion in the brain.

In a secondary analysis of a study involving 552 hypothyroid patients randomized to LT4 or LT4/LT3, the prevalence of Thr92Ala homozygosity was 16%, and psychological well being in patients with the deiodinase 2 polymorphism improved significantly more on combination therapy than with LT4 alone (J. Clin. Endocrinol. Metab. 2009;94:1623-9).

The fact that the Thr92Ala polymorphism is present in only 16% of individuals on thyroid hormone therapy might explain why so many randomized trials of LT4 versus combination therapy were negative: With study populations of only 20-141 patients, the trials would have been underpowered to detect a significant difference in treatment effect. Unfortunately, genetic testing for deiodinase polymorphisms is not commercially available, the endocrinologist observed.

When he does resort to combination therapy, Dr. McDermott prescribes it in an LT4:LT3 ratio of 10-14:1 to mimic normal thyroid secretion. He generally has patients take LT3 twice daily, with the second dose no later than about 6 p.m. so it doesn’t interfere with sleep. Once-daily slow-release formulations of LT3 are available in Europe and work very well. Several companies are interested in developing a slow-release LT3 for the United States, which would be a welcome development, according to Dr. McDermott.

Another option, once all else has been tried and failed, is to switch to another brand of LT4, he continued. Some patients may have adverse reactions to the various dyes and fillers contained in LT4 pills. When this is a potential concern, levothyroxine sodium (Tirosint), approved by the Food and Drug Administration a couple of years ago, is an attractive option. The LT4 in Tirosint is contained in oil in a liquid gelcap with no dyes or fillers, differentiating it from all other brand name and generic products, Dr. McDermott noted.

He emphasized the importance of avoiding overtreatment with LT4 in an attempt to improve quality of life in patients with residual symptoms despite a TSH of 0.5-2.0 mU/L. Subclinical hyperthyroidism as defined by a TSH below 0.1 mU/L has been shown to significantly increase the risk of hip and spine fractures, atrial fibrillation, and cardiovascular mortality.

Dr. McDermott reported having no financial conflicts.

ESTES PARK, COLO. – Adding liothyronine is a reasonable treatment strategy when symptoms of hypothyroidism persist on optimal levothyroxine alone, according to Dr. Michael T. McDermott, professor of medicine and clinical pharmacology and director of endocrinology and diabetes practice at the University of Colorado Hospital, Aurora.

Combination levothyroxine/liothyronine (LT4/LT3) therapy is supported by a biologically plausible mechanism of benefit in symptomatic patients who are biochemically euthyroid on LT4. But it’s a step that belongs near the bottom of the management plan for the difficult hypothyroid patient. It should be considered only after other actions have been taken, including a search for coexisting autoimmune conditions or other medical illnesses, Dr. McDermott said at an update on internal medicine sponsored by the University of Colorado.

Every physician who treats hypothyroidism has patients who experience lingering fatigue, memory problems, and other symptoms even though their on-treatment TSH is in the target range of 0.5-2.0 mU/L. Five published studies underscore just how common this situation is. Dr. McDermott cited as an example a study of 397 hypothyroid patients with a TSH in the goal range; 34% scored in the abnormal range on the short-form General Health Questionnaire and 49% had elevated scores on a thyroid symptom-specific questionnaire (Clin. Endocrinol. [Oxf.] 2002;57:577-85).

These are patients who require further general medical evaluation. Their symptoms may be due to a coexistent autoimmune disease. After all, autoimmune diseases tend to cluster. Indeed, when British investigators did a systematic work-up of 495 patients with Hashimoto’s thyroiditis, they found a 14% prevalence of another autoimmune disease. Leading the way was rheumatoid arthritis, present in 4% of subjects. The Hashimoto’s thyroiditis group also had greater than 10-fold increased relative risks of celiac disease, vitiligo, SLE, and Addison’s disease (Am. J. Med. 2010;183:e1-9).

Alternatively, the patient’s lingering symptoms may be due in part to Hashimoto’s thyroiditis itself rather than to hypothyroidism per se. A study of 426 euthyroid women with goiter undergoing thyroidectomy showed that those with antithyroperoxidase antibodies had higher levels of fatigue, nervousness, and irritability, and lower quality of life (Thyroid 2011;21:161-7).

Dr. McDermott routinely obtains a serum 25 vitamin D measurement in his difficult cases of hypothyroidism, since low vitamin D levels are a common cause of fatigue. He also encourages patients with lingering symptoms to eat a well-balanced diet and get regular exercise and sleep, and he refers them for treatment of depression when indicated.

Only after doing all that, does he consider adding LT3. Combined LT4/LT3 therapy is controversial. The first-ever randomized controlled clinical trial was positive (N. Engl. J. Med. 1999;340:424-9), but it was followed by a spate of negative studies. Some physicians closed the book on this treatment strategy after a meta-analysis of all 11 randomized trials showed combination therapy was without benefit (J. Clin. Endocrinol. Metab. 2006; 91: 2,592-9).

However, more recent work has shown that a relatively common polymorphism of the deiodinase 2 gene known as Thr92Ala may predict less responsiveness of psychological symptoms of hypothyroidism to optimal LT4 monotherapy. Deiodinase 2 is responsible for maintaining brain T3 levels, and there is evidence to indicate that the Thr92Ala polymorphism subtly impairs T4 to T3 conversion in the brain.

In a secondary analysis of a study involving 552 hypothyroid patients randomized to LT4 or LT4/LT3, the prevalence of Thr92Ala homozygosity was 16%, and psychological well being in patients with the deiodinase 2 polymorphism improved significantly more on combination therapy than with LT4 alone (J. Clin. Endocrinol. Metab. 2009;94:1623-9).

The fact that the Thr92Ala polymorphism is present in only 16% of individuals on thyroid hormone therapy might explain why so many randomized trials of LT4 versus combination therapy were negative: With study populations of only 20-141 patients, the trials would have been underpowered to detect a significant difference in treatment effect. Unfortunately, genetic testing for deiodinase polymorphisms is not commercially available, the endocrinologist observed.

When he does resort to combination therapy, Dr. McDermott prescribes it in an LT4:LT3 ratio of 10-14:1 to mimic normal thyroid secretion. He generally has patients take LT3 twice daily, with the second dose no later than about 6 p.m. so it doesn’t interfere with sleep. Once-daily slow-release formulations of LT3 are available in Europe and work very well. Several companies are interested in developing a slow-release LT3 for the United States, which would be a welcome development, according to Dr. McDermott.

Another option, once all else has been tried and failed, is to switch to another brand of LT4, he continued. Some patients may have adverse reactions to the various dyes and fillers contained in LT4 pills. When this is a potential concern, levothyroxine sodium (Tirosint), approved by the Food and Drug Administration a couple of years ago, is an attractive option. The LT4 in Tirosint is contained in oil in a liquid gelcap with no dyes or fillers, differentiating it from all other brand name and generic products, Dr. McDermott noted.

He emphasized the importance of avoiding overtreatment with LT4 in an attempt to improve quality of life in patients with residual symptoms despite a TSH of 0.5-2.0 mU/L. Subclinical hyperthyroidism as defined by a TSH below 0.1 mU/L has been shown to significantly increase the risk of hip and spine fractures, atrial fibrillation, and cardiovascular mortality.

Dr. McDermott reported having no financial conflicts.