Rheumatoid Arthritis

The Janus kinase inhibitor tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis, has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate, the Food and Drug Administration announced on Nov. 6.

Tofacitinib is a small-molecule inhibitor of the Janus kinase (JAK) pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.

It has been approved with a Risk Evaluation and Mitigation Strategy (REMS) that addresses the serious risks associated with treatment, and a requirement that the manufacturer, Pfizer, conduct a postmarketing study, according to the FDA’s statement announcing the approval.

Approval was based on the results of seven studies, which found that patients with moderately to severely active RA had improvements in clinical response and physical functioning, when compared with those on placebo. Tofacitinib was associated with an increased risk of serious infections, including opportunistic infections; tuberculosis; cancers; and lymphoma, which are described in the boxed warning in the drug’s label, the FDA said.

Treatment was also associated with increases in cholesterol and liver enzymes, and decreased blood counts. The REMS consists of a Medication Guide that includes information for patients about the drug’s safety and a communication plan that will educate health care providers about the serious risks associated with the treatment.

The postmarketing study will compare two doses of tofacitinib with another approved treatment for RA.

At a meeting in May, the FDA’s Arthritis Advisory Committee voted 8 to 2 to recommend approval of tofacitinib for patients with RA, although panel members had lingering safety concerns.

Pfizer is marketing the drug as Xeljanz. Another JAK inhibitor, ruxolitinib (Jakafi), was approved to treat myelofibrosis in 2011.

The Janus kinase inhibitor tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis, has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate, the Food and Drug Administration announced on Nov. 6.

Tofacitinib is a small-molecule inhibitor of the Janus kinase (JAK) pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.

It has been approved with a Risk Evaluation and Mitigation Strategy (REMS) that addresses the serious risks associated with treatment, and a requirement that the manufacturer, Pfizer, conduct a postmarketing study, according to the FDA’s statement announcing the approval.

Approval was based on the results of seven studies, which found that patients with moderately to severely active RA had improvements in clinical response and physical functioning, when compared with those on placebo. Tofacitinib was associated with an increased risk of serious infections, including opportunistic infections; tuberculosis; cancers; and lymphoma, which are described in the boxed warning in the drug’s label, the FDA said.

Treatment was also associated with increases in cholesterol and liver enzymes, and decreased blood counts. The REMS consists of a Medication Guide that includes information for patients about the drug’s safety and a communication plan that will educate health care providers about the serious risks associated with the treatment.

The postmarketing study will compare two doses of tofacitinib with another approved treatment for RA.

At a meeting in May, the FDA’s Arthritis Advisory Committee voted 8 to 2 to recommend approval of tofacitinib for patients with RA, although panel members had lingering safety concerns.

Pfizer is marketing the drug as Xeljanz. Another JAK inhibitor, ruxolitinib (Jakafi), was approved to treat myelofibrosis in 2011.

The Janus kinase inhibitor tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis, has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate, the Food and Drug Administration announced on Nov. 6.

Tofacitinib is a small-molecule inhibitor of the Janus kinase (JAK) pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.

It has been approved with a Risk Evaluation and Mitigation Strategy (REMS) that addresses the serious risks associated with treatment, and a requirement that the manufacturer, Pfizer, conduct a postmarketing study, according to the FDA’s statement announcing the approval.

Approval was based on the results of seven studies, which found that patients with moderately to severely active RA had improvements in clinical response and physical functioning, when compared with those on placebo. Tofacitinib was associated with an increased risk of serious infections, including opportunistic infections; tuberculosis; cancers; and lymphoma, which are described in the boxed warning in the drug’s label, the FDA said.

Treatment was also associated with increases in cholesterol and liver enzymes, and decreased blood counts. The REMS consists of a Medication Guide that includes information for patients about the drug’s safety and a communication plan that will educate health care providers about the serious risks associated with the treatment.

The postmarketing study will compare two doses of tofacitinib with another approved treatment for RA.

At a meeting in May, the FDA’s Arthritis Advisory Committee voted 8 to 2 to recommend approval of tofacitinib for patients with RA, although panel members had lingering safety concerns.

Pfizer is marketing the drug as Xeljanz. Another JAK inhibitor, ruxolitinib (Jakafi), was approved to treat myelofibrosis in 2011.

The outbreak of fungal meningitis caused by contaminated methylprednisolone has topped 200 patients and is likely to include more, according to a review article on the subject published online in the New England Journal of Medicine. The article was written in an attempt to answer some of the "numerous questions have been raised by physicians, patients who received injections from the implicated lots, and the public."

Despite the fact that the first case reported found the mold Aspergillus fumigatus as the cause of the meningitis, this organism was not been detected in any of the subsequent 200-plus cases and is no longer considered as the basis for appropriate treatment. Instead, the fungal plant pathogen, Exserohilum rostratum, has been cultured or identified using polymerase chain reaction assay from cerebrospinal fluid in at least 25 patients and was detected in at least one unopened vial from the implicated lot of methylprednisolone, according to Dr. Carol A. Kaufman of the Veterans Affairs Ann Arbor (Mich.) Healthcare System, and her colleagues from Alabama and Texas.

E. rostratum is a "black mold" containing melanin in its cell wall. It is rarely infectious to humans and is usually restricted to mild diseases, such as allergic sinusitis, keratitis, and localized soft-tissue infection. In tissues, E. rostratum has the same appearance of irregular, beaded hyphae as seen in many other dematiaceous fungi, and unlike the rarely septate, ribbonlike hyphae of Mucorales fungi or the acutely branching, hyaline hyphae of aspergillus species.

Recommendations for treating this rare infection are based on small case series, individual case reports, and personal experience, according to the authors of the review article (N. Engl. J. Med. 2012 [doi:10.10156/NEJMra1212617]). The Centers for Disease Control and Prevention is providing information on the outbreak with daily updates, along with appropriate diagnostic testing and treatment details on its website, according to the authors.

Initially, when the causative agent was not known and the only detected microorganism was A. fumigatus, high doses of both liposomal amphotericin B and voriconazole were recommended. Once the primary pathogen was determined to be the black mold, however, monotherapy with voriconazole was recommended, except for the sickest patients or those who had substantial side-effects to the drug. For these, amphotericin B could still play a role, the said.

Although exserohilum species are susceptible to available antifungals, for some strains, the minimal inhibitor concentration for the usually recommended agents, including voriconazole, is increased. Thus, susceptibility testing is advised, they added.

Because of the potential toxic effects of voriconazole, especially in the large doses recommended, and the host of drug-drug interactions in which it is involved, prophylactic use is not recommended, the authors said. They noted that side effects included visual hallucinations, which have been noted in patients treated during the outbreak. Other side effects can include photopsia, nausea, and hepatic enzyme elevation.

"Without objective evidence of infection in the cerebrospinal fluid, treatment is not recommended. However, patients who have symptoms should be monitored closely, and if there is even subtle progression of symptoms, a repeat lumbar puncture should be performed immediately. If the number of white cells has increased [reaching 5 mm³or more], then empirical antifungal treatment should be initiated immediately," the authors stated.

"It is encouraging to note that clinically apparent disease has developed in only a small percentage of exposed patients. Management recommendations will almost assuredly change as more information becomes available regarding the pathogenesis of these infections," they concluded.

Dr. Kaufman and the other authors reported having no relevant disclosures for their review paper.

The outbreak of fungal meningitis caused by contaminated methylprednisolone has topped 200 patients and is likely to include more, according to a review article on the subject published online in the New England Journal of Medicine. The article was written in an attempt to answer some of the "numerous questions have been raised by physicians, patients who received injections from the implicated lots, and the public."

Despite the fact that the first case reported found the mold Aspergillus fumigatus as the cause of the meningitis, this organism was not been detected in any of the subsequent 200-plus cases and is no longer considered as the basis for appropriate treatment. Instead, the fungal plant pathogen, Exserohilum rostratum, has been cultured or identified using polymerase chain reaction assay from cerebrospinal fluid in at least 25 patients and was detected in at least one unopened vial from the implicated lot of methylprednisolone, according to Dr. Carol A. Kaufman of the Veterans Affairs Ann Arbor (Mich.) Healthcare System, and her colleagues from Alabama and Texas.

E. rostratum is a "black mold" containing melanin in its cell wall. It is rarely infectious to humans and is usually restricted to mild diseases, such as allergic sinusitis, keratitis, and localized soft-tissue infection. In tissues, E. rostratum has the same appearance of irregular, beaded hyphae as seen in many other dematiaceous fungi, and unlike the rarely septate, ribbonlike hyphae of Mucorales fungi or the acutely branching, hyaline hyphae of aspergillus species.

Recommendations for treating this rare infection are based on small case series, individual case reports, and personal experience, according to the authors of the review article (N. Engl. J. Med. 2012 [doi:10.10156/NEJMra1212617]). The Centers for Disease Control and Prevention is providing information on the outbreak with daily updates, along with appropriate diagnostic testing and treatment details on its website, according to the authors.

Initially, when the causative agent was not known and the only detected microorganism was A. fumigatus, high doses of both liposomal amphotericin B and voriconazole were recommended. Once the primary pathogen was determined to be the black mold, however, monotherapy with voriconazole was recommended, except for the sickest patients or those who had substantial side-effects to the drug. For these, amphotericin B could still play a role, the said.

Although exserohilum species are susceptible to available antifungals, for some strains, the minimal inhibitor concentration for the usually recommended agents, including voriconazole, is increased. Thus, susceptibility testing is advised, they added.

Because of the potential toxic effects of voriconazole, especially in the large doses recommended, and the host of drug-drug interactions in which it is involved, prophylactic use is not recommended, the authors said. They noted that side effects included visual hallucinations, which have been noted in patients treated during the outbreak. Other side effects can include photopsia, nausea, and hepatic enzyme elevation.

"Without objective evidence of infection in the cerebrospinal fluid, treatment is not recommended. However, patients who have symptoms should be monitored closely, and if there is even subtle progression of symptoms, a repeat lumbar puncture should be performed immediately. If the number of white cells has increased [reaching 5 mm³or more], then empirical antifungal treatment should be initiated immediately," the authors stated.

"It is encouraging to note that clinically apparent disease has developed in only a small percentage of exposed patients. Management recommendations will almost assuredly change as more information becomes available regarding the pathogenesis of these infections," they concluded.

Dr. Kaufman and the other authors reported having no relevant disclosures for their review paper.

The outbreak of fungal meningitis caused by contaminated methylprednisolone has topped 200 patients and is likely to include more, according to a review article on the subject published online in the New England Journal of Medicine. The article was written in an attempt to answer some of the "numerous questions have been raised by physicians, patients who received injections from the implicated lots, and the public."

Despite the fact that the first case reported found the mold Aspergillus fumigatus as the cause of the meningitis, this organism was not been detected in any of the subsequent 200-plus cases and is no longer considered as the basis for appropriate treatment. Instead, the fungal plant pathogen, Exserohilum rostratum, has been cultured or identified using polymerase chain reaction assay from cerebrospinal fluid in at least 25 patients and was detected in at least one unopened vial from the implicated lot of methylprednisolone, according to Dr. Carol A. Kaufman of the Veterans Affairs Ann Arbor (Mich.) Healthcare System, and her colleagues from Alabama and Texas.

E. rostratum is a "black mold" containing melanin in its cell wall. It is rarely infectious to humans and is usually restricted to mild diseases, such as allergic sinusitis, keratitis, and localized soft-tissue infection. In tissues, E. rostratum has the same appearance of irregular, beaded hyphae as seen in many other dematiaceous fungi, and unlike the rarely septate, ribbonlike hyphae of Mucorales fungi or the acutely branching, hyaline hyphae of aspergillus species.

Recommendations for treating this rare infection are based on small case series, individual case reports, and personal experience, according to the authors of the review article (N. Engl. J. Med. 2012 [doi:10.10156/NEJMra1212617]). The Centers for Disease Control and Prevention is providing information on the outbreak with daily updates, along with appropriate diagnostic testing and treatment details on its website, according to the authors.

Initially, when the causative agent was not known and the only detected microorganism was A. fumigatus, high doses of both liposomal amphotericin B and voriconazole were recommended. Once the primary pathogen was determined to be the black mold, however, monotherapy with voriconazole was recommended, except for the sickest patients or those who had substantial side-effects to the drug. For these, amphotericin B could still play a role, the said.

Although exserohilum species are susceptible to available antifungals, for some strains, the minimal inhibitor concentration for the usually recommended agents, including voriconazole, is increased. Thus, susceptibility testing is advised, they added.

Because of the potential toxic effects of voriconazole, especially in the large doses recommended, and the host of drug-drug interactions in which it is involved, prophylactic use is not recommended, the authors said. They noted that side effects included visual hallucinations, which have been noted in patients treated during the outbreak. Other side effects can include photopsia, nausea, and hepatic enzyme elevation.

"Without objective evidence of infection in the cerebrospinal fluid, treatment is not recommended. However, patients who have symptoms should be monitored closely, and if there is even subtle progression of symptoms, a repeat lumbar puncture should be performed immediately. If the number of white cells has increased [reaching 5 mm³or more], then empirical antifungal treatment should be initiated immediately," the authors stated.

"It is encouraging to note that clinically apparent disease has developed in only a small percentage of exposed patients. Management recommendations will almost assuredly change as more information becomes available regarding the pathogenesis of these infections," they concluded.

Dr. Kaufman and the other authors reported having no relevant disclosures for their review paper.

Listeria and Salmonella infections in patients with rheumatoid arthritis decreased by 73% after they received updated advice about consuming foods likely to carry those pathogens.

The incidence of these infections dropped from 5/10,000 person-years to 1/10,000 after the 2006 educational campaign, Ms. Rebecca Davies reported.

Courtesy CDC/Janice Haney Carr

"Although it may not be possible to eliminate this infection risk entirely, this ... shows the positive impact of informing patients of how to modify their risk of adverse events," wrote Ms. Davies, a research assistant at the University of Manchester, England, and her colleagues.

Because tumor necrosis factor is important in controlling intracellular bacterial infections, suppressing the protein can increase the risk of such infections. The British Society for Rheumatology’s Rheumatoid Arthritis Register tracks such events. In 2006, recognizing an early signal of increased infections by food-borne pathogens, the group advised patients taking the drugs to avoid high-risk foods, including raw eggs and raw poultry, unpasteurized milk, and some cheeses.

Ms. Davies and her colleagues reviewed the records of almost 12,000 patients enrolled in the registry – 9,376 of whom were taking anti-TNF-alpha drugs before 2006, and 2,347 of whom were taking them afterward. All were followed until death, last recorded visit, or through March 31, 2011. The review included data on all listeria and salmonella infections in the patients.

Nine patients who had ever taken one of the drugs experienced an infection before 2006 (four taking etanercept, three taking infliximab, and two taking adalimumab). Six patients experienced infections after 2006 (two etanercept, two infliximab, and two adalimumab). The crude incidence rates were 5/10,000 before 2006 and 1.4/10,000 afterward – a rate ratio of 0.27 and a 73% reduction.

The investigators found a similar result when they examined rates only in patients who were on therapy during the times in question. The incidence ratio was 4.6/10,000 before 2006, and 1.2 after 2006 – a rate ratio of 0.26 (74% reduction).

"This reduction was also found when allowing for a 90-day ‘lag window’ following treatment, accounting for any residual effect of the drug," the investigators noted.

The British Society for Rheumatology funded the study. The society receives funding from Abbott Laboratories, Merck, Pfizer, Roche, Swedish Orphan Biovitrum, and UCB. The society also contributes to rheumatology research at the University of Manchester. The paper did not note financial declarations from any of the individual authors.

Listeria and Salmonella infections in patients with rheumatoid arthritis decreased by 73% after they received updated advice about consuming foods likely to carry those pathogens.

The incidence of these infections dropped from 5/10,000 person-years to 1/10,000 after the 2006 educational campaign, Ms. Rebecca Davies reported.

Courtesy CDC/Janice Haney Carr

"Although it may not be possible to eliminate this infection risk entirely, this ... shows the positive impact of informing patients of how to modify their risk of adverse events," wrote Ms. Davies, a research assistant at the University of Manchester, England, and her colleagues.

Because tumor necrosis factor is important in controlling intracellular bacterial infections, suppressing the protein can increase the risk of such infections. The British Society for Rheumatology’s Rheumatoid Arthritis Register tracks such events. In 2006, recognizing an early signal of increased infections by food-borne pathogens, the group advised patients taking the drugs to avoid high-risk foods, including raw eggs and raw poultry, unpasteurized milk, and some cheeses.

Ms. Davies and her colleagues reviewed the records of almost 12,000 patients enrolled in the registry – 9,376 of whom were taking anti-TNF-alpha drugs before 2006, and 2,347 of whom were taking them afterward. All were followed until death, last recorded visit, or through March 31, 2011. The review included data on all listeria and salmonella infections in the patients.

Nine patients who had ever taken one of the drugs experienced an infection before 2006 (four taking etanercept, three taking infliximab, and two taking adalimumab). Six patients experienced infections after 2006 (two etanercept, two infliximab, and two adalimumab). The crude incidence rates were 5/10,000 before 2006 and 1.4/10,000 afterward – a rate ratio of 0.27 and a 73% reduction.

The investigators found a similar result when they examined rates only in patients who were on therapy during the times in question. The incidence ratio was 4.6/10,000 before 2006, and 1.2 after 2006 – a rate ratio of 0.26 (74% reduction).

"This reduction was also found when allowing for a 90-day ‘lag window’ following treatment, accounting for any residual effect of the drug," the investigators noted.

The British Society for Rheumatology funded the study. The society receives funding from Abbott Laboratories, Merck, Pfizer, Roche, Swedish Orphan Biovitrum, and UCB. The society also contributes to rheumatology research at the University of Manchester. The paper did not note financial declarations from any of the individual authors.

Listeria and Salmonella infections in patients with rheumatoid arthritis decreased by 73% after they received updated advice about consuming foods likely to carry those pathogens.

The incidence of these infections dropped from 5/10,000 person-years to 1/10,000 after the 2006 educational campaign, Ms. Rebecca Davies reported.

Courtesy CDC/Janice Haney Carr

"Although it may not be possible to eliminate this infection risk entirely, this ... shows the positive impact of informing patients of how to modify their risk of adverse events," wrote Ms. Davies, a research assistant at the University of Manchester, England, and her colleagues.

Because tumor necrosis factor is important in controlling intracellular bacterial infections, suppressing the protein can increase the risk of such infections. The British Society for Rheumatology’s Rheumatoid Arthritis Register tracks such events. In 2006, recognizing an early signal of increased infections by food-borne pathogens, the group advised patients taking the drugs to avoid high-risk foods, including raw eggs and raw poultry, unpasteurized milk, and some cheeses.

Ms. Davies and her colleagues reviewed the records of almost 12,000 patients enrolled in the registry – 9,376 of whom were taking anti-TNF-alpha drugs before 2006, and 2,347 of whom were taking them afterward. All were followed until death, last recorded visit, or through March 31, 2011. The review included data on all listeria and salmonella infections in the patients.

Nine patients who had ever taken one of the drugs experienced an infection before 2006 (four taking etanercept, three taking infliximab, and two taking adalimumab). Six patients experienced infections after 2006 (two etanercept, two infliximab, and two adalimumab). The crude incidence rates were 5/10,000 before 2006 and 1.4/10,000 afterward – a rate ratio of 0.27 and a 73% reduction.

The investigators found a similar result when they examined rates only in patients who were on therapy during the times in question. The incidence ratio was 4.6/10,000 before 2006, and 1.2 after 2006 – a rate ratio of 0.26 (74% reduction).

"This reduction was also found when allowing for a 90-day ‘lag window’ following treatment, accounting for any residual effect of the drug," the investigators noted.

The British Society for Rheumatology funded the study. The society receives funding from Abbott Laboratories, Merck, Pfizer, Roche, Swedish Orphan Biovitrum, and UCB. The society also contributes to rheumatology research at the University of Manchester. The paper did not note financial declarations from any of the individual authors.

A series of inspections conducted in October at the New England Compounding Center – the facility at the heart of the investigation into a recent fungal meningitis outbreak – found nonsterile conditions and contaminated vials of the steroid methylprednisolone acetate.

Investigators with the Food and Drug Administration’s New England District Office visited the New England Compounding Center (NECC) facility in Framingham, Mass., during 7 days in October. The FDA released the observations from those inspections on Oct. 26.

On Oct. 2, the FDA investigators noticed what appeared to be "greenish-black foreign matter" in 83 vials of methylprednisolone acetate and "white filamentous material" among another 17 vials from the same bin. The vials were marked with the same lot number as a shipment that was sent to customers in August and September. Although a sample taken by the company in August found that lot of vials to be to be sterile, the FDA’s own laboratory analysis found the presence of viable microbial growth in 50 of the 50 unopened vials it tested.

The investigators also discovered problems in the NECC’s clean rooms, which are enclosed spaces used to help reduce the risk of microbial contamination when processing sterile drug products. For instance, the firm’s own environmental monitoring reports revealed that between January and September 2012, there was bacteria and mold in multiple locations, including on surfaces within the clean rooms. There was no documentation that the company attempted to correct these problem, even though the contamination was above acceptable limits, according to the FDA.

FDA officials refused to characterize the observations made by its investigators or to comment on any other details of the agency’s ongoing investigation of the NECC.

A series of inspections conducted in October at the New England Compounding Center – the facility at the heart of the investigation into a recent fungal meningitis outbreak – found nonsterile conditions and contaminated vials of the steroid methylprednisolone acetate.

Investigators with the Food and Drug Administration’s New England District Office visited the New England Compounding Center (NECC) facility in Framingham, Mass., during 7 days in October. The FDA released the observations from those inspections on Oct. 26.

On Oct. 2, the FDA investigators noticed what appeared to be "greenish-black foreign matter" in 83 vials of methylprednisolone acetate and "white filamentous material" among another 17 vials from the same bin. The vials were marked with the same lot number as a shipment that was sent to customers in August and September. Although a sample taken by the company in August found that lot of vials to be to be sterile, the FDA’s own laboratory analysis found the presence of viable microbial growth in 50 of the 50 unopened vials it tested.

The investigators also discovered problems in the NECC’s clean rooms, which are enclosed spaces used to help reduce the risk of microbial contamination when processing sterile drug products. For instance, the firm’s own environmental monitoring reports revealed that between January and September 2012, there was bacteria and mold in multiple locations, including on surfaces within the clean rooms. There was no documentation that the company attempted to correct these problem, even though the contamination was above acceptable limits, according to the FDA.

FDA officials refused to characterize the observations made by its investigators or to comment on any other details of the agency’s ongoing investigation of the NECC.

A series of inspections conducted in October at the New England Compounding Center – the facility at the heart of the investigation into a recent fungal meningitis outbreak – found nonsterile conditions and contaminated vials of the steroid methylprednisolone acetate.

Investigators with the Food and Drug Administration’s New England District Office visited the New England Compounding Center (NECC) facility in Framingham, Mass., during 7 days in October. The FDA released the observations from those inspections on Oct. 26.

On Oct. 2, the FDA investigators noticed what appeared to be "greenish-black foreign matter" in 83 vials of methylprednisolone acetate and "white filamentous material" among another 17 vials from the same bin. The vials were marked with the same lot number as a shipment that was sent to customers in August and September. Although a sample taken by the company in August found that lot of vials to be to be sterile, the FDA’s own laboratory analysis found the presence of viable microbial growth in 50 of the 50 unopened vials it tested.

The investigators also discovered problems in the NECC’s clean rooms, which are enclosed spaces used to help reduce the risk of microbial contamination when processing sterile drug products. For instance, the firm’s own environmental monitoring reports revealed that between January and September 2012, there was bacteria and mold in multiple locations, including on surfaces within the clean rooms. There was no documentation that the company attempted to correct these problem, even though the contamination was above acceptable limits, according to the FDA.

FDA officials refused to characterize the observations made by its investigators or to comment on any other details of the agency’s ongoing investigation of the NECC.

Infections have developed in one joint each in two individuals who were injected with fungus-contaminated methylprednisolone acetate in the weeks or months preceding the ongoing outbreak, according to a teleconference hosted Oct. 16 by the Food and Drug Administration and the Centers for Disease Control and Prevention.

The indications for those joint injections were not discussed at the briefing, but rheumatologists commonly use methylprednisolone injections in joints affected by rheumatoid arthritis or osteoarthritis to reduce inflammation and ease pain.

Dr. Tom Chiller, a medical epidemiologist at the Division of Foodborne, Waterborne and Environmental Diseases at the CDC, noted that both infected joints were ankles that had been injected with fungus-contaminated methylprednisolone acetate manufactured by the New England Compounding Center (NECC) in Framingham, Mass. That plant has been shut down because inspection by the FDA showed that the conditions were unsterile.

Neither culture nor polymerase chain reaction of synovial fluid aspirated from the infected ankles has grown any fungus. However, because bacteria and crystals have been ruled out as a cause of these two cases of septic arthritic and both patients received intra-articular injections with the contaminated steroid solution, investigators feel certain the patients have fungal joint infections, according to Dr. Chiller.

Three kinds of fungus have been identified in patients with fungal infections associated with the contaminated NECC products. Aspergillus was identified as the cause of the index case of fungal meningitis. Two types of black mold have been cultured from meningitis patients: Exserohilum rostratum and Cladosporium.

In total, as of Oct. 16, there have been 233 confirmed cases of fungal infection in people who received injections, usually epidural, of contaminated steroid in solution, according to Dr. Melissa Schaefer, medical officer in the Division of Healthcare Quality Promotion at the CDC’s National Center for Emerging and Zoonotic Infectious Diseases. Among these people there have been 15 deaths, all from meningitis.

One particularly challenging aspect of this outbreak for rheumatologists is the length of incubation of septic arthritis because of a fungus.

The FDA has advised physicians who used NECC products dated May 21, 2012 or later, to contact their patients to check on their well being. Most of the patients given epidural injections with the contaminated solution are likely to present within 1-2 weeks.

The latency period of a fungus infection in a joint, however, may be months, according to Dr. Peter G. Pappas, professor of medicine in the division of infectious diseases at the University of Alabama at Birmingham, who participated in the CDC teleconference.

Patients with septic arthritis often limp into the office months after the onset of symptoms to seek medical care, he said.

The CDC has revised its treatment guidance for septic arthritis in cases of suspected fungal infection Dr. Chiller said that in cases of suspected fungal septic arthritis, the CDC now recommends empiric treatment with voriconazole (Vfend), beginning with a loading dose of 6 mg/kg every 12 hours for two doses, followed by 4 mg/kg every 12 hours for the duration of treatment. A lipid formulation of amphotericin B at a dose of 5 mg/kg IV daily should be considered in addition to voriconazole in patients with severe joint infection and/or clinical instability. Administration of 1L normal saline prior to infusion may be considered to minimize risk of nephrotoxicity. Providers and patients should be aware of and monitor for potential adverse effects of amphotericin B formulations.

The CDC plans to update the guidance on diagnosing fungal septic arthritis on Oct. 17 or 18.

The source of the outbreak is NECC, a compounding pharmacy that operated in violation of the law on a number of levels.

Infections have developed in one joint each in two individuals who were injected with fungus-contaminated methylprednisolone acetate in the weeks or months preceding the ongoing outbreak, according to a teleconference hosted Oct. 16 by the Food and Drug Administration and the Centers for Disease Control and Prevention.

The indications for those joint injections were not discussed at the briefing, but rheumatologists commonly use methylprednisolone injections in joints affected by rheumatoid arthritis or osteoarthritis to reduce inflammation and ease pain.

Dr. Tom Chiller, a medical epidemiologist at the Division of Foodborne, Waterborne and Environmental Diseases at the CDC, noted that both infected joints were ankles that had been injected with fungus-contaminated methylprednisolone acetate manufactured by the New England Compounding Center (NECC) in Framingham, Mass. That plant has been shut down because inspection by the FDA showed that the conditions were unsterile.

Neither culture nor polymerase chain reaction of synovial fluid aspirated from the infected ankles has grown any fungus. However, because bacteria and crystals have been ruled out as a cause of these two cases of septic arthritic and both patients received intra-articular injections with the contaminated steroid solution, investigators feel certain the patients have fungal joint infections, according to Dr. Chiller.

Three kinds of fungus have been identified in patients with fungal infections associated with the contaminated NECC products. Aspergillus was identified as the cause of the index case of fungal meningitis. Two types of black mold have been cultured from meningitis patients: Exserohilum rostratum and Cladosporium.

In total, as of Oct. 16, there have been 233 confirmed cases of fungal infection in people who received injections, usually epidural, of contaminated steroid in solution, according to Dr. Melissa Schaefer, medical officer in the Division of Healthcare Quality Promotion at the CDC’s National Center for Emerging and Zoonotic Infectious Diseases. Among these people there have been 15 deaths, all from meningitis.

One particularly challenging aspect of this outbreak for rheumatologists is the length of incubation of septic arthritis because of a fungus.

The FDA has advised physicians who used NECC products dated May 21, 2012 or later, to contact their patients to check on their well being. Most of the patients given epidural injections with the contaminated solution are likely to present within 1-2 weeks.

The latency period of a fungus infection in a joint, however, may be months, according to Dr. Peter G. Pappas, professor of medicine in the division of infectious diseases at the University of Alabama at Birmingham, who participated in the CDC teleconference.

Patients with septic arthritis often limp into the office months after the onset of symptoms to seek medical care, he said.

The CDC has revised its treatment guidance for septic arthritis in cases of suspected fungal infection Dr. Chiller said that in cases of suspected fungal septic arthritis, the CDC now recommends empiric treatment with voriconazole (Vfend), beginning with a loading dose of 6 mg/kg every 12 hours for two doses, followed by 4 mg/kg every 12 hours for the duration of treatment. A lipid formulation of amphotericin B at a dose of 5 mg/kg IV daily should be considered in addition to voriconazole in patients with severe joint infection and/or clinical instability. Administration of 1L normal saline prior to infusion may be considered to minimize risk of nephrotoxicity. Providers and patients should be aware of and monitor for potential adverse effects of amphotericin B formulations.

The CDC plans to update the guidance on diagnosing fungal septic arthritis on Oct. 17 or 18.

The source of the outbreak is NECC, a compounding pharmacy that operated in violation of the law on a number of levels.

Infections have developed in one joint each in two individuals who were injected with fungus-contaminated methylprednisolone acetate in the weeks or months preceding the ongoing outbreak, according to a teleconference hosted Oct. 16 by the Food and Drug Administration and the Centers for Disease Control and Prevention.

The indications for those joint injections were not discussed at the briefing, but rheumatologists commonly use methylprednisolone injections in joints affected by rheumatoid arthritis or osteoarthritis to reduce inflammation and ease pain.

Dr. Tom Chiller, a medical epidemiologist at the Division of Foodborne, Waterborne and Environmental Diseases at the CDC, noted that both infected joints were ankles that had been injected with fungus-contaminated methylprednisolone acetate manufactured by the New England Compounding Center (NECC) in Framingham, Mass. That plant has been shut down because inspection by the FDA showed that the conditions were unsterile.

Neither culture nor polymerase chain reaction of synovial fluid aspirated from the infected ankles has grown any fungus. However, because bacteria and crystals have been ruled out as a cause of these two cases of septic arthritic and both patients received intra-articular injections with the contaminated steroid solution, investigators feel certain the patients have fungal joint infections, according to Dr. Chiller.

Three kinds of fungus have been identified in patients with fungal infections associated with the contaminated NECC products. Aspergillus was identified as the cause of the index case of fungal meningitis. Two types of black mold have been cultured from meningitis patients: Exserohilum rostratum and Cladosporium.

In total, as of Oct. 16, there have been 233 confirmed cases of fungal infection in people who received injections, usually epidural, of contaminated steroid in solution, according to Dr. Melissa Schaefer, medical officer in the Division of Healthcare Quality Promotion at the CDC’s National Center for Emerging and Zoonotic Infectious Diseases. Among these people there have been 15 deaths, all from meningitis.

One particularly challenging aspect of this outbreak for rheumatologists is the length of incubation of septic arthritis because of a fungus.

The FDA has advised physicians who used NECC products dated May 21, 2012 or later, to contact their patients to check on their well being. Most of the patients given epidural injections with the contaminated solution are likely to present within 1-2 weeks.

The latency period of a fungus infection in a joint, however, may be months, according to Dr. Peter G. Pappas, professor of medicine in the division of infectious diseases at the University of Alabama at Birmingham, who participated in the CDC teleconference.

Patients with septic arthritis often limp into the office months after the onset of symptoms to seek medical care, he said.

The CDC has revised its treatment guidance for septic arthritis in cases of suspected fungal infection Dr. Chiller said that in cases of suspected fungal septic arthritis, the CDC now recommends empiric treatment with voriconazole (Vfend), beginning with a loading dose of 6 mg/kg every 12 hours for two doses, followed by 4 mg/kg every 12 hours for the duration of treatment. A lipid formulation of amphotericin B at a dose of 5 mg/kg IV daily should be considered in addition to voriconazole in patients with severe joint infection and/or clinical instability. Administration of 1L normal saline prior to infusion may be considered to minimize risk of nephrotoxicity. Providers and patients should be aware of and monitor for potential adverse effects of amphotericin B formulations.

The CDC plans to update the guidance on diagnosing fungal septic arthritis on Oct. 17 or 18.

The source of the outbreak is NECC, a compounding pharmacy that operated in violation of the law on a number of levels.

NEWPORT BEACH, CALIF. – Rituximab is a good remission induction agent in patients with small vessel vasculitis, such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, according to Dr. Leonard Calabrese, chair of clinical immunology and professor of medicine at the Cleveland Clinic.

It appears to be a better choice in some patients than cyclophosphamide, the traditional option, although cyclophosphamide remains the standard of care for remission induction in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, he said at Perspectives in Rheumatic Diseases 2012.

The Food and Drug Administration approved rituximab for small vessel vasculitis in 2011 based on a trial that pitted cyclophosphamide induction and azathioprine maintenance against a 6-month regimen of rituximab, with patients in both arms of the study receiving prednisone. They all had severe but not fulminant Wegener’s granulomatosis or microscopic polyangiitis; over half had renal involvement.

Of the 99 rituximab patients, 63 (64%) reached the primary end point of steroid-free remission at 6 months, compared with 52 (53%) of the 98 cyclophosphamide patients. (N. Engl. J. Med. 2010;363:221-32).

At 18 months follow-up, 36% of rituximab patients remained in remission without treatment.

"All the trends in the trial favored rituximab. Patients who came in with [new] disease had equal outcomes. If they had relapsed on [cyclophosphamide], rituximab was significantly better," Dr. Calabrese said.

Given the results, and the fact that rituximab might have fewer long-term side effects, it "is favored as the initial therapy for patients who would otherwise be offered cyclophosphamide. Clearly, rituximab is the drug of choice for [cyclophosphamide] relapsers," he said.

Also based on the results, Dr. Calabrese said he is comfortable stopping therapy and observing patients "with new-onset moderate disease that melts away" with rituximab.

But for patients with a relapsing course or who respond only partially to rituximab, "I don’t favor observation. I think repeated rituximab or an antimetabolite is in order. Most the time, I’ve been doing repeated rituximab," he said.

The optimal rituximab patient remains unclear. "There’s more work to be done on the [study] results. We are looking for predictors," he said.

Meanwhile, "cyclophosphamide and apheresis are still my go-to therapies for patients who are ventilator dependent or have a pulmonary or renal presentation," Dr. Calabrese said.

Azathioprine, methotrexate, leflunomide, and mycophenolate are among the options for step-down therapy when patients are treated traditionally with cyclophosphamide for remission, but findings from a recent study showed "there’s no doubt that azathioprine is more effective than mycophenolate for remission maintenance. Azathioprine, in those who can tolerate it, is quite good," he said (JAMA 2010;304:2381-8).

When patients don’t have life-threatening target organ involvement – no red blood–cell casts in the urine, no hypoxic lung involvement, and normal creatinines and liver functions – methotrexate alone might be the best option.

Such patients "tend to be young and have upper-airway-limited disease. These people are very good methotrexate candidates, 20-25 mg/day with high dose glucocorticoids," he said.

For mild, limited disease, "methotrexate works great," he said.

Dr. Calabrese is a consultant for Aventis, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer. He is a speaker for Amgen. The meeting was held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

NEWPORT BEACH, CALIF. – Rituximab is a good remission induction agent in patients with small vessel vasculitis, such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, according to Dr. Leonard Calabrese, chair of clinical immunology and professor of medicine at the Cleveland Clinic.

It appears to be a better choice in some patients than cyclophosphamide, the traditional option, although cyclophosphamide remains the standard of care for remission induction in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, he said at Perspectives in Rheumatic Diseases 2012.

The Food and Drug Administration approved rituximab for small vessel vasculitis in 2011 based on a trial that pitted cyclophosphamide induction and azathioprine maintenance against a 6-month regimen of rituximab, with patients in both arms of the study receiving prednisone. They all had severe but not fulminant Wegener’s granulomatosis or microscopic polyangiitis; over half had renal involvement.

Of the 99 rituximab patients, 63 (64%) reached the primary end point of steroid-free remission at 6 months, compared with 52 (53%) of the 98 cyclophosphamide patients. (N. Engl. J. Med. 2010;363:221-32).

At 18 months follow-up, 36% of rituximab patients remained in remission without treatment.

"All the trends in the trial favored rituximab. Patients who came in with [new] disease had equal outcomes. If they had relapsed on [cyclophosphamide], rituximab was significantly better," Dr. Calabrese said.

Given the results, and the fact that rituximab might have fewer long-term side effects, it "is favored as the initial therapy for patients who would otherwise be offered cyclophosphamide. Clearly, rituximab is the drug of choice for [cyclophosphamide] relapsers," he said.

Also based on the results, Dr. Calabrese said he is comfortable stopping therapy and observing patients "with new-onset moderate disease that melts away" with rituximab.

But for patients with a relapsing course or who respond only partially to rituximab, "I don’t favor observation. I think repeated rituximab or an antimetabolite is in order. Most the time, I’ve been doing repeated rituximab," he said.

The optimal rituximab patient remains unclear. "There’s more work to be done on the [study] results. We are looking for predictors," he said.

Meanwhile, "cyclophosphamide and apheresis are still my go-to therapies for patients who are ventilator dependent or have a pulmonary or renal presentation," Dr. Calabrese said.

Azathioprine, methotrexate, leflunomide, and mycophenolate are among the options for step-down therapy when patients are treated traditionally with cyclophosphamide for remission, but findings from a recent study showed "there’s no doubt that azathioprine is more effective than mycophenolate for remission maintenance. Azathioprine, in those who can tolerate it, is quite good," he said (JAMA 2010;304:2381-8).

When patients don’t have life-threatening target organ involvement – no red blood–cell casts in the urine, no hypoxic lung involvement, and normal creatinines and liver functions – methotrexate alone might be the best option.

Such patients "tend to be young and have upper-airway-limited disease. These people are very good methotrexate candidates, 20-25 mg/day with high dose glucocorticoids," he said.

For mild, limited disease, "methotrexate works great," he said.

Dr. Calabrese is a consultant for Aventis, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer. He is a speaker for Amgen. The meeting was held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

NEWPORT BEACH, CALIF. – Rituximab is a good remission induction agent in patients with small vessel vasculitis, such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, according to Dr. Leonard Calabrese, chair of clinical immunology and professor of medicine at the Cleveland Clinic.

It appears to be a better choice in some patients than cyclophosphamide, the traditional option, although cyclophosphamide remains the standard of care for remission induction in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, he said at Perspectives in Rheumatic Diseases 2012.

The Food and Drug Administration approved rituximab for small vessel vasculitis in 2011 based on a trial that pitted cyclophosphamide induction and azathioprine maintenance against a 6-month regimen of rituximab, with patients in both arms of the study receiving prednisone. They all had severe but not fulminant Wegener’s granulomatosis or microscopic polyangiitis; over half had renal involvement.

Of the 99 rituximab patients, 63 (64%) reached the primary end point of steroid-free remission at 6 months, compared with 52 (53%) of the 98 cyclophosphamide patients. (N. Engl. J. Med. 2010;363:221-32).

At 18 months follow-up, 36% of rituximab patients remained in remission without treatment.

"All the trends in the trial favored rituximab. Patients who came in with [new] disease had equal outcomes. If they had relapsed on [cyclophosphamide], rituximab was significantly better," Dr. Calabrese said.

Given the results, and the fact that rituximab might have fewer long-term side effects, it "is favored as the initial therapy for patients who would otherwise be offered cyclophosphamide. Clearly, rituximab is the drug of choice for [cyclophosphamide] relapsers," he said.

Also based on the results, Dr. Calabrese said he is comfortable stopping therapy and observing patients "with new-onset moderate disease that melts away" with rituximab.

But for patients with a relapsing course or who respond only partially to rituximab, "I don’t favor observation. I think repeated rituximab or an antimetabolite is in order. Most the time, I’ve been doing repeated rituximab," he said.

The optimal rituximab patient remains unclear. "There’s more work to be done on the [study] results. We are looking for predictors," he said.

Meanwhile, "cyclophosphamide and apheresis are still my go-to therapies for patients who are ventilator dependent or have a pulmonary or renal presentation," Dr. Calabrese said.

Azathioprine, methotrexate, leflunomide, and mycophenolate are among the options for step-down therapy when patients are treated traditionally with cyclophosphamide for remission, but findings from a recent study showed "there’s no doubt that azathioprine is more effective than mycophenolate for remission maintenance. Azathioprine, in those who can tolerate it, is quite good," he said (JAMA 2010;304:2381-8).

When patients don’t have life-threatening target organ involvement – no red blood–cell casts in the urine, no hypoxic lung involvement, and normal creatinines and liver functions – methotrexate alone might be the best option.

Such patients "tend to be young and have upper-airway-limited disease. These people are very good methotrexate candidates, 20-25 mg/day with high dose glucocorticoids," he said.

For mild, limited disease, "methotrexate works great," he said.

Dr. Calabrese is a consultant for Aventis, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer. He is a speaker for Amgen. The meeting was held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

People with psoriatic arthritis tend to be young and therefore less likely to have a primary care physician on hand to manage cardiovascular risk factors associated with their PsA. That leaves it to rheumatologists to help these patients lower their blood lipid levels, manage their weight, and tend to other important heart disease risks, according to Dr. Christopher T. Ritchlin, Professor of Rheumatology, Medicine, and Allergy/Immunology and Director the Clinical Immunology Research Center, at the University of Rochester (N.Y.) School of Medicine and Dentistry. This interview was conducted at the annual Perspectives in Rheumatic Diseases conference.

People with psoriatic arthritis tend to be young and therefore less likely to have a primary care physician on hand to manage cardiovascular risk factors associated with their PsA. That leaves it to rheumatologists to help these patients lower their blood lipid levels, manage their weight, and tend to other important heart disease risks, according to Dr. Christopher T. Ritchlin, Professor of Rheumatology, Medicine, and Allergy/Immunology and Director the Clinical Immunology Research Center, at the University of Rochester (N.Y.) School of Medicine and Dentistry. This interview was conducted at the annual Perspectives in Rheumatic Diseases conference.

People with psoriatic arthritis tend to be young and therefore less likely to have a primary care physician on hand to manage cardiovascular risk factors associated with their PsA. That leaves it to rheumatologists to help these patients lower their blood lipid levels, manage their weight, and tend to other important heart disease risks, according to Dr. Christopher T. Ritchlin, Professor of Rheumatology, Medicine, and Allergy/Immunology and Director the Clinical Immunology Research Center, at the University of Rochester (N.Y.) School of Medicine and Dentistry. This interview was conducted at the annual Perspectives in Rheumatic Diseases conference.

Oct. 12, 2012, marks the 16th annual World Arthritis Day. This year’s theme – "Move to Improve" – aims to remind both physicians and patients of the benefits of regular exercise in the management of arthritis.

The emphasis on exercise echoes the recommendations earlier this year from the American College of Rheumatology that physicians should counsel people with osteoarthritis to exercise as part of their therapy. These benefits include reducing pain, delaying disability, and improving mobility, function, and mood, according to the Centers for Disease Control and Prevention.

Courtesy Thinkstockphotos.com

Arthritis is the most-common cause of disability in the United States, according to the CDC. By 2030, the agency projects that 67 million persons will be affected by arthritis and, among those, 25 million will be limited in their usual activities because of the disease. Exercise has the benefit of helping patients limit their disability, although some patients may be concerned, wrongly, that exercise may worsen their symptoms.

All forms of arthritis are associated with an increased risk for cardiovascular disease, with a recent report linking osteoarthritis to a higher risk for heart disease.

Other research has shown gout to increase the risk for heart disease, and the link between rheumatoid arthritis and earlier onset of ischemic heart disease is well established.

Physical activity also can help people with arthritis to manage other chronic conditions, like diabetes and heart disease, according to the CDC. Physicians have been increasingly pushing patients, especially those with chronic conditions, to get fit. The CDC recommends that all adults, including those with arthritis, exercise at least 2.5 hours of exercise weekly (or 30 minutes, 5 times a week), spread out in 10-to-15-minute segments throughout the day, if necessary.

Established in 1996, by Arthritis and Rheumatism International (ARI), World Arthritis Day is celebrated every Oct. 12. Its themes change regularly and this is the second time it has highlighted the benefits of exercise. Previous themes include "Let’s Work Together," in 2009, which focused on work-related challenges, such as working from home and paid employment. Nearly 50 million adults and 300,000 children have some form or arthritis or other rheumatic condition, making arthritis the most common cause of disability in the United States, according to the CDC.

Oct. 12, 2012, marks the 16th annual World Arthritis Day. This year’s theme – "Move to Improve" – aims to remind both physicians and patients of the benefits of regular exercise in the management of arthritis.

The emphasis on exercise echoes the recommendations earlier this year from the American College of Rheumatology that physicians should counsel people with osteoarthritis to exercise as part of their therapy. These benefits include reducing pain, delaying disability, and improving mobility, function, and mood, according to the Centers for Disease Control and Prevention.

Courtesy Thinkstockphotos.com

Arthritis is the most-common cause of disability in the United States, according to the CDC. By 2030, the agency projects that 67 million persons will be affected by arthritis and, among those, 25 million will be limited in their usual activities because of the disease. Exercise has the benefit of helping patients limit their disability, although some patients may be concerned, wrongly, that exercise may worsen their symptoms.

All forms of arthritis are associated with an increased risk for cardiovascular disease, with a recent report linking osteoarthritis to a higher risk for heart disease.

Other research has shown gout to increase the risk for heart disease, and the link between rheumatoid arthritis and earlier onset of ischemic heart disease is well established.

Physical activity also can help people with arthritis to manage other chronic conditions, like diabetes and heart disease, according to the CDC. Physicians have been increasingly pushing patients, especially those with chronic conditions, to get fit. The CDC recommends that all adults, including those with arthritis, exercise at least 2.5 hours of exercise weekly (or 30 minutes, 5 times a week), spread out in 10-to-15-minute segments throughout the day, if necessary.

Established in 1996, by Arthritis and Rheumatism International (ARI), World Arthritis Day is celebrated every Oct. 12. Its themes change regularly and this is the second time it has highlighted the benefits of exercise. Previous themes include "Let’s Work Together," in 2009, which focused on work-related challenges, such as working from home and paid employment. Nearly 50 million adults and 300,000 children have some form or arthritis or other rheumatic condition, making arthritis the most common cause of disability in the United States, according to the CDC.

Oct. 12, 2012, marks the 16th annual World Arthritis Day. This year’s theme – "Move to Improve" – aims to remind both physicians and patients of the benefits of regular exercise in the management of arthritis.

The emphasis on exercise echoes the recommendations earlier this year from the American College of Rheumatology that physicians should counsel people with osteoarthritis to exercise as part of their therapy. These benefits include reducing pain, delaying disability, and improving mobility, function, and mood, according to the Centers for Disease Control and Prevention.

Courtesy Thinkstockphotos.com

Arthritis is the most-common cause of disability in the United States, according to the CDC. By 2030, the agency projects that 67 million persons will be affected by arthritis and, among those, 25 million will be limited in their usual activities because of the disease. Exercise has the benefit of helping patients limit their disability, although some patients may be concerned, wrongly, that exercise may worsen their symptoms.

All forms of arthritis are associated with an increased risk for cardiovascular disease, with a recent report linking osteoarthritis to a higher risk for heart disease.

Other research has shown gout to increase the risk for heart disease, and the link between rheumatoid arthritis and earlier onset of ischemic heart disease is well established.

Physical activity also can help people with arthritis to manage other chronic conditions, like diabetes and heart disease, according to the CDC. Physicians have been increasingly pushing patients, especially those with chronic conditions, to get fit. The CDC recommends that all adults, including those with arthritis, exercise at least 2.5 hours of exercise weekly (or 30 minutes, 5 times a week), spread out in 10-to-15-minute segments throughout the day, if necessary.

Established in 1996, by Arthritis and Rheumatism International (ARI), World Arthritis Day is celebrated every Oct. 12. Its themes change regularly and this is the second time it has highlighted the benefits of exercise. Previous themes include "Let’s Work Together," in 2009, which focused on work-related challenges, such as working from home and paid employment. Nearly 50 million adults and 300,000 children have some form or arthritis or other rheumatic condition, making arthritis the most common cause of disability in the United States, according to the CDC.

Adults with new-onset rheumatoid arthritis showed a 75% prevalence of moderate to severe periodontal disease in a study profiling the oral microbiota in RA. The results were published in the October issue of Arthritis & Rheumatism.

The presence of periodontal disease was particularly striking because these study subjects were young, were mostly nonsmokers, and had never been treated with potentially immunosuppressive steroids or disease-modifying antirheumatic drugs (DMARDs), said Dr. Jose U. Scher, director of the arthritis clinic at New York University Hospital for Joint Diseases, and his associates.

The study finding is "consistent with the prevailing speculation" that Porphyromonas gingivalis and other species may be triggering factors for rheumatoid arthritis (RA) in susceptible people. But it also raises the intriguing alternative possibility that both the gums and the joints may be targets of the same autoimmune process and that periodontitis may be an extraarticular characteristic of RA, the investigators said.

RA has long been associated with both oral microbes and periodontal disease, but "data describing the subgingival microbiota in patients with RA are virtually nonexistent." Dr. Scher and his colleagues "aimed to determine the periodontal status of RA patients and healthy controls and to directly correlate, for the first time, the presence and abundance of subgingival microbiota with RA status."

They assessed 31 consecutive adults who presented to the university’s rheumatology clinics with new-onset RA; 34 adults who had chronic RA (mean duration, 5 years), most of whom were receiving oral and biologic DMARDs; and 18 healthy control subjects matched to the new-onset RA patients for age, sex, and ethnicity.

Oral samples were obtained from all study subjects using subgingival biofilm from the six sites with the greatest extent of periodontal disease. DNA was then extracted from the samples to identify the microorganisms that were present.

The prevalence of moderate to severe periodontal disease was 75% in patients with new-onset RA, equivalent to the 75% prevalence in patients with chronic RA and significantly higher than the 39% prevalence in the healthy controls. The rate in the control group was consistent with the 30%-40% rate found in the general population, the researchers said (Arthritis Rheum. 2012;64:3083-94).

This finding is consistent with the widely accepted idea that periodontal disease may be a risk factor for the development of RA. In fact, "it is reasonable to posit that a particular Porphyromonas species with defined virulent attributes (i.e., invasion properties, high PAD enzyme activity) might serve as a triggering factor for RA in susceptible individuals," they said.

Two species of bacteria, Prevotella and Leptotrichia, were found in many samples from patients with new-onset RA but in none of the samples from control subjects. The prevalence of Prevotella was 32.2% and that of Leptotrichia was 25.8% in new-onset RA. These organisms merit further study as possible periodontal triggers of RA, along with Porphyromonas gingivalis, Dr. Scher and his associates said.

Three of the most virulent periodontopathic bacteria – Tannerella, Treponema, and Porphyromonas – were more abundant in patients with new-onset RA than in those with chronic RA. It may be that these organisms diminish as patients begin therapeutic regimens, particularly those containing immunomodulatory agents that have antibacterial properties, such as methotrexate or hydroxychloroquine.

Dr. Scher and his colleagues noted that exposure to bacteria at other body sites, such as the lung or intestine, may also contribute to the development of RA. Their next project is to assess the role of the intestinal microbiota in the disease.

This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No financial conflicts of interest were reported.

Adults with new-onset rheumatoid arthritis showed a 75% prevalence of moderate to severe periodontal disease in a study profiling the oral microbiota in RA. The results were published in the October issue of Arthritis & Rheumatism.

The presence of periodontal disease was particularly striking because these study subjects were young, were mostly nonsmokers, and had never been treated with potentially immunosuppressive steroids or disease-modifying antirheumatic drugs (DMARDs), said Dr. Jose U. Scher, director of the arthritis clinic at New York University Hospital for Joint Diseases, and his associates.

The study finding is "consistent with the prevailing speculation" that Porphyromonas gingivalis and other species may be triggering factors for rheumatoid arthritis (RA) in susceptible people. But it also raises the intriguing alternative possibility that both the gums and the joints may be targets of the same autoimmune process and that periodontitis may be an extraarticular characteristic of RA, the investigators said.

RA has long been associated with both oral microbes and periodontal disease, but "data describing the subgingival microbiota in patients with RA are virtually nonexistent." Dr. Scher and his colleagues "aimed to determine the periodontal status of RA patients and healthy controls and to directly correlate, for the first time, the presence and abundance of subgingival microbiota with RA status."

They assessed 31 consecutive adults who presented to the university’s rheumatology clinics with new-onset RA; 34 adults who had chronic RA (mean duration, 5 years), most of whom were receiving oral and biologic DMARDs; and 18 healthy control subjects matched to the new-onset RA patients for age, sex, and ethnicity.

Oral samples were obtained from all study subjects using subgingival biofilm from the six sites with the greatest extent of periodontal disease. DNA was then extracted from the samples to identify the microorganisms that were present.

The prevalence of moderate to severe periodontal disease was 75% in patients with new-onset RA, equivalent to the 75% prevalence in patients with chronic RA and significantly higher than the 39% prevalence in the healthy controls. The rate in the control group was consistent with the 30%-40% rate found in the general population, the researchers said (Arthritis Rheum. 2012;64:3083-94).

This finding is consistent with the widely accepted idea that periodontal disease may be a risk factor for the development of RA. In fact, "it is reasonable to posit that a particular Porphyromonas species with defined virulent attributes (i.e., invasion properties, high PAD enzyme activity) might serve as a triggering factor for RA in susceptible individuals," they said.

Two species of bacteria, Prevotella and Leptotrichia, were found in many samples from patients with new-onset RA but in none of the samples from control subjects. The prevalence of Prevotella was 32.2% and that of Leptotrichia was 25.8% in new-onset RA. These organisms merit further study as possible periodontal triggers of RA, along with Porphyromonas gingivalis, Dr. Scher and his associates said.

Three of the most virulent periodontopathic bacteria – Tannerella, Treponema, and Porphyromonas – were more abundant in patients with new-onset RA than in those with chronic RA. It may be that these organisms diminish as patients begin therapeutic regimens, particularly those containing immunomodulatory agents that have antibacterial properties, such as methotrexate or hydroxychloroquine.

Dr. Scher and his colleagues noted that exposure to bacteria at other body sites, such as the lung or intestine, may also contribute to the development of RA. Their next project is to assess the role of the intestinal microbiota in the disease.

This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No financial conflicts of interest were reported.

Adults with new-onset rheumatoid arthritis showed a 75% prevalence of moderate to severe periodontal disease in a study profiling the oral microbiota in RA. The results were published in the October issue of Arthritis & Rheumatism.

The presence of periodontal disease was particularly striking because these study subjects were young, were mostly nonsmokers, and had never been treated with potentially immunosuppressive steroids or disease-modifying antirheumatic drugs (DMARDs), said Dr. Jose U. Scher, director of the arthritis clinic at New York University Hospital for Joint Diseases, and his associates.

The study finding is "consistent with the prevailing speculation" that Porphyromonas gingivalis and other species may be triggering factors for rheumatoid arthritis (RA) in susceptible people. But it also raises the intriguing alternative possibility that both the gums and the joints may be targets of the same autoimmune process and that periodontitis may be an extraarticular characteristic of RA, the investigators said.

RA has long been associated with both oral microbes and periodontal disease, but "data describing the subgingival microbiota in patients with RA are virtually nonexistent." Dr. Scher and his colleagues "aimed to determine the periodontal status of RA patients and healthy controls and to directly correlate, for the first time, the presence and abundance of subgingival microbiota with RA status."

They assessed 31 consecutive adults who presented to the university’s rheumatology clinics with new-onset RA; 34 adults who had chronic RA (mean duration, 5 years), most of whom were receiving oral and biologic DMARDs; and 18 healthy control subjects matched to the new-onset RA patients for age, sex, and ethnicity.

Oral samples were obtained from all study subjects using subgingival biofilm from the six sites with the greatest extent of periodontal disease. DNA was then extracted from the samples to identify the microorganisms that were present.

The prevalence of moderate to severe periodontal disease was 75% in patients with new-onset RA, equivalent to the 75% prevalence in patients with chronic RA and significantly higher than the 39% prevalence in the healthy controls. The rate in the control group was consistent with the 30%-40% rate found in the general population, the researchers said (Arthritis Rheum. 2012;64:3083-94).

This finding is consistent with the widely accepted idea that periodontal disease may be a risk factor for the development of RA. In fact, "it is reasonable to posit that a particular Porphyromonas species with defined virulent attributes (i.e., invasion properties, high PAD enzyme activity) might serve as a triggering factor for RA in susceptible individuals," they said.

Two species of bacteria, Prevotella and Leptotrichia, were found in many samples from patients with new-onset RA but in none of the samples from control subjects. The prevalence of Prevotella was 32.2% and that of Leptotrichia was 25.8% in new-onset RA. These organisms merit further study as possible periodontal triggers of RA, along with Porphyromonas gingivalis, Dr. Scher and his associates said.

Three of the most virulent periodontopathic bacteria – Tannerella, Treponema, and Porphyromonas – were more abundant in patients with new-onset RA than in those with chronic RA. It may be that these organisms diminish as patients begin therapeutic regimens, particularly those containing immunomodulatory agents that have antibacterial properties, such as methotrexate or hydroxychloroquine.

Dr. Scher and his colleagues noted that exposure to bacteria at other body sites, such as the lung or intestine, may also contribute to the development of RA. Their next project is to assess the role of the intestinal microbiota in the disease.

This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No financial conflicts of interest were reported.

NEWPORT BEACH, CALIF. – Methotrexate alone is sufficient treatment for some cases of early rheumatoid arthritis, according to Dr. Daniel Furst.

Almost a third of patients "responded well to methotrexate alone" in several studies. For those who do, "long-term success can be anticipated with methotrexate alone," 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.

Because of that, "I try a patient on methotrexate first, and if she does really well, it’s good enough. If after 3 months or so she’s not doing really well, then adding other choices" – tumor necrosis factor inhibitors or other options – "makes a lot of sense," said Dr. Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In one of the studies proving the point, 493 patients with rheumatoid arthritis (RA) for less than a year and a mean disease activity score in 28 joints (DAS28) of 5.72 were treated with 20 mg/wk of methotrexate for 3-4 months. In 143 (29%) patients, DAS28 scores fell below 3.2, indicating low disease activity; 84 (17%) went into remission. Male gender, higher age, and lower baseline DAS28 all predicted response to methotrexate. Responders continued to improve throughout the 12 months of the study (Lancet 2009;374:459-66).

Etanercept may be a good add-on if patients need it. Although early RA patients seem to do as well clinically whether they receive methotrexate plus etanercept or triple therapy – methotrexate, sulfasalazine, and hydroxychloroquine – "on x-rays, triple therapy is not as good. The biologic, when added to methotrexate, slows x-ray progression more than triple therapy," Dr. Furst said (Arthritis Rheum. 2012;64:2824-35).

Methotrexate slows x-ray progression, too, but not as much as a biologic agent, he noted.

Corticosteroids may boost the effect of methotrexate in early RA, at least at first. In one study, 117 patients with symptoms for less than a year were randomized to methotrexate plus 10 mg/day of prednisone; 119 were randomized to methotrexate plus placebo (Ann. Intern. Med. 2012;156:329-39).

At first, methotrexate plus prednisone was better at reducing disease activity and physical disability, "but by about a year, there was [little] difference. What this says to me, and this is found in several studies, is that prednisone is pretty good stuff early on, but by 1 year you’ve lost most of your advantage," Dr. Furst said.

He reminded his audience that "you are immunosuppressing these patients, so before you start, you really ought to [check for] hepatitis B and C" as well as tuberculosis, and vaccinate patients as needed. Human papillomavirus and herpes zoster virus vaccinations "make sense when you are going to immunosuppress somebody," he said.

Dr. Furst disclosed relationships with Abbott, Amgen, Bristol-Myers Squibb, GlaxoSmithKline Novartis, Roche, and several other pharmaceutical companies. SDEF and this news organization are owned by Frontline Medical Communications.

NEWPORT BEACH, CALIF. – Methotrexate alone is sufficient treatment for some cases of early rheumatoid arthritis, according to Dr. Daniel Furst.

Almost a third of patients "responded well to methotrexate alone" in several studies. For those who do, "long-term success can be anticipated with methotrexate alone," 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.

Because of that, "I try a patient on methotrexate first, and if she does really well, it’s good enough. If after 3 months or so she’s not doing really well, then adding other choices" – tumor necrosis factor inhibitors or other options – "makes a lot of sense," said Dr. Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In one of the studies proving the point, 493 patients with rheumatoid arthritis (RA) for less than a year and a mean disease activity score in 28 joints (DAS28) of 5.72 were treated with 20 mg/wk of methotrexate for 3-4 months. In 143 (29%) patients, DAS28 scores fell below 3.2, indicating low disease activity; 84 (17%) went into remission. Male gender, higher age, and lower baseline DAS28 all predicted response to methotrexate. Responders continued to improve throughout the 12 months of the study (Lancet 2009;374:459-66).

Etanercept may be a good add-on if patients need it. Although early RA patients seem to do as well clinically whether they receive methotrexate plus etanercept or triple therapy – methotrexate, sulfasalazine, and hydroxychloroquine – "on x-rays, triple therapy is not as good. The biologic, when added to methotrexate, slows x-ray progression more than triple therapy," Dr. Furst said (Arthritis Rheum. 2012;64:2824-35).

Methotrexate slows x-ray progression, too, but not as much as a biologic agent, he noted.

Corticosteroids may boost the effect of methotrexate in early RA, at least at first. In one study, 117 patients with symptoms for less than a year were randomized to methotrexate plus 10 mg/day of prednisone; 119 were randomized to methotrexate plus placebo (Ann. Intern. Med. 2012;156:329-39).

At first, methotrexate plus prednisone was better at reducing disease activity and physical disability, "but by about a year, there was [little] difference. What this says to me, and this is found in several studies, is that prednisone is pretty good stuff early on, but by 1 year you’ve lost most of your advantage," Dr. Furst said.

He reminded his audience that "you are immunosuppressing these patients, so before you start, you really ought to [check for] hepatitis B and C" as well as tuberculosis, and vaccinate patients as needed. Human papillomavirus and herpes zoster virus vaccinations "make sense when you are going to immunosuppress somebody," he said.

Dr. Furst disclosed relationships with Abbott, Amgen, Bristol-Myers Squibb, GlaxoSmithKline Novartis, Roche, and several other pharmaceutical companies. SDEF and this news organization are owned by Frontline Medical Communications.

NEWPORT BEACH, CALIF. – Methotrexate alone is sufficient treatment for some cases of early rheumatoid arthritis, according to Dr. Daniel Furst.

Almost a third of patients "responded well to methotrexate alone" in several studies. For those who do, "long-term success can be anticipated with methotrexate alone," 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.

Because of that, "I try a patient on methotrexate first, and if she does really well, it’s good enough. If after 3 months or so she’s not doing really well, then adding other choices" – tumor necrosis factor inhibitors or other options – "makes a lot of sense," said Dr. Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In one of the studies proving the point, 493 patients with rheumatoid arthritis (RA) for less than a year and a mean disease activity score in 28 joints (DAS28) of 5.72 were treated with 20 mg/wk of methotrexate for 3-4 months. In 143 (29%) patients, DAS28 scores fell below 3.2, indicating low disease activity; 84 (17%) went into remission. Male gender, higher age, and lower baseline DAS28 all predicted response to methotrexate. Responders continued to improve throughout the 12 months of the study (Lancet 2009;374:459-66).

Etanercept may be a good add-on if patients need it. Although early RA patients seem to do as well clinically whether they receive methotrexate plus etanercept or triple therapy – methotrexate, sulfasalazine, and hydroxychloroquine – "on x-rays, triple therapy is not as good. The biologic, when added to methotrexate, slows x-ray progression more than triple therapy," Dr. Furst said (Arthritis Rheum. 2012;64:2824-35).

Methotrexate slows x-ray progression, too, but not as much as a biologic agent, he noted.

Corticosteroids may boost the effect of methotrexate in early RA, at least at first. In one study, 117 patients with symptoms for less than a year were randomized to methotrexate plus 10 mg/day of prednisone; 119 were randomized to methotrexate plus placebo (Ann. Intern. Med. 2012;156:329-39).

At first, methotrexate plus prednisone was better at reducing disease activity and physical disability, "but by about a year, there was [little] difference. What this says to me, and this is found in several studies, is that prednisone is pretty good stuff early on, but by 1 year you’ve lost most of your advantage," Dr. Furst said.

He reminded his audience that "you are immunosuppressing these patients, so before you start, you really ought to [check for] hepatitis B and C" as well as tuberculosis, and vaccinate patients as needed. Human papillomavirus and herpes zoster virus vaccinations "make sense when you are going to immunosuppress somebody," he said.

Dr. Furst disclosed relationships with Abbott, Amgen, Bristol-Myers Squibb, GlaxoSmithKline Novartis, Roche, and several other pharmaceutical companies. SDEF and this news organization are owned by Frontline Medical Communications.