Psoriasis

GLASGOW – Biologic treatment for rheumatoid arthritis does not increase the overall risk of solid cancers beyond that of more traditional, nonbiologic drugs, according to long-awaited data from the British Society for Rheumatology Biologics Register.

At a median follow-up of almost 5 years, the adjusted hazard ratio for all solid cancers was 0.88 (95% confidence interval, 0.65-1.17) in a comparison between anti–tumor necrosis factor (anti-TNF)-alpha therapy and nonbiologic disease-modifying antirheumatic drugs (nbDMARDs, n = 3,543) in patients without a prior history of cancer.

There was no significant difference in cancer risk between the anti-TNF drugs included in the analysis, namely etanercept (adjusted hazard ratio, 0.94; 95% CI, 0.68-1.29), infliximab (aHR, 0.87; 95% CI, 0.61-1.25), and adalimumab (aHR, 0.81; 95% CI, 0.57-1.14) versus nbDMARDs. Neither duration of follow-up nor the overall site where tumors occurred had any effect on the occurrence of solid cancers.

These data lend further support to the general safety of TNF inhibitors, and add to findings reported from the British Society for Rheumatology Biologics Register (BSRBR) and other European registries, such as the Danish Biologics Registry (DANBIO), with regard to malignancy (Rheumatology News, June 2011, p. 22).

"We do still need further follow-up to address site-specific [cancer] risk and to allow for longer latency," said Dr. Louise Mercer, May 3, at the British Society for Rheumatology annual conference (Rheumatology 2012;51:iii40, abstract O37).

Dr. Mercer, a clinical research fellow at the Arthritis Research UK Epidemiology Unit, University of Manchester (England), noted that that cancer risk is already higher in patients with RA than in the general population (Rheumatology News, April 2011, p. 31). However, these latest findings from the BSRBR highlight that the use of biologic therapy doesn’t appear to add to this risk over that seen with nbDMARDs.

Data on 11,719 patients without a history of cancer who were enrolled in the BSRBR between 2001 and 2009 were used for the current analysis. Data after 2009 were not considered in order to allow for the lag time in cancer reporting from the U.K.’s National Cancer Registry into the Biologics Register. A group of 3,543 patients treated with nbDMARDs was used as the reference population.

Data adjustment took account of patients’ age at baseline, gender, duration of disease, use of nonsteroidal anti-inflammatory drugs, comorbidities, and age at time of enrollment in the U.K.-based register.

A total of 295 cancers were reported in patients treated with anti-TNF agents during a mean follow up of 4.6 years, giving a crude cancer rate of 63 per 10,000 patient-years. A total of 91 cancers were reported in patients treated with nbDMARDs over a median follow-up of 3.4 years, representing a crude cancer rate of 84 per 10,000 patient years.

With regard to the site of cancer, anti-TNFs appeared to be associated with a lower risk of lung cancer (aHR, 0.89; 95% CI, 0.46-1.74) and breast cancer (aHR, 0.99; 95% CI, 0.51-1.92) than were nbDMARDs. There was an increase in the risk of colorectal cancer (HR, 1.21; 95% CI, 0.54-2.70), but "the confidence intervals have become wider," Dr. Mercer observed.

Data on patients with a prior history of cancer have already been published by the team (Arthritis Care Res. 2010;62:755-63), but new data on patients with cervical carcinoma in situ (CIS) were reported during a poster presentation at the meeting (Rheumatology 2012;51:iii77, abstract 70).

Considering data collated through March 2011, 238 women had a prior history of cervical CIS – 48 of 2,654 (1.8%) women treated with nbDMARDs and 190 of 9,084 (2.1%) treated with anti-TNFs. Two women subsequently developed genitourinary cancer – both were treated with nbDMARDs. The rate of incident cancer was 13 per 1,000 person-years (95% CI, 2-45).

Dr. Mercer and her associates noted that there was a low level of reporting cervical CIS, which could reflect rheumatologists not being aware of abnormal cervical changes or choosing not to report in situ cancers or these prior cancers at baseline.

They concluded that "there were no new or recurrent female genital cancers among women with preexisting cervical CIS selected for treatment with anti-TNF," which should prove reassuring to women who may have a history of cervical abnormalities and who are considering anti-TNF therapy.

The BSRBR is funded by a grant from the British Society for Rheumatology. The BSR receives funding from Abbott Laboratories, Swedish Orphan Biovitrum (SOBI), Merck, Pfizer, Roche Products, and UCB Pharma. This income finances a separate contract between the BSR and the University of Manchester, which provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Dr. Mercer reported having no personal conflicts of interest.

GLASGOW – Biologic treatment for rheumatoid arthritis does not increase the overall risk of solid cancers beyond that of more traditional, nonbiologic drugs, according to long-awaited data from the British Society for Rheumatology Biologics Register.

At a median follow-up of almost 5 years, the adjusted hazard ratio for all solid cancers was 0.88 (95% confidence interval, 0.65-1.17) in a comparison between anti–tumor necrosis factor (anti-TNF)-alpha therapy and nonbiologic disease-modifying antirheumatic drugs (nbDMARDs, n = 3,543) in patients without a prior history of cancer.

There was no significant difference in cancer risk between the anti-TNF drugs included in the analysis, namely etanercept (adjusted hazard ratio, 0.94; 95% CI, 0.68-1.29), infliximab (aHR, 0.87; 95% CI, 0.61-1.25), and adalimumab (aHR, 0.81; 95% CI, 0.57-1.14) versus nbDMARDs. Neither duration of follow-up nor the overall site where tumors occurred had any effect on the occurrence of solid cancers.

These data lend further support to the general safety of TNF inhibitors, and add to findings reported from the British Society for Rheumatology Biologics Register (BSRBR) and other European registries, such as the Danish Biologics Registry (DANBIO), with regard to malignancy (Rheumatology News, June 2011, p. 22).

"We do still need further follow-up to address site-specific [cancer] risk and to allow for longer latency," said Dr. Louise Mercer, May 3, at the British Society for Rheumatology annual conference (Rheumatology 2012;51:iii40, abstract O37).

Dr. Mercer, a clinical research fellow at the Arthritis Research UK Epidemiology Unit, University of Manchester (England), noted that that cancer risk is already higher in patients with RA than in the general population (Rheumatology News, April 2011, p. 31). However, these latest findings from the BSRBR highlight that the use of biologic therapy doesn’t appear to add to this risk over that seen with nbDMARDs.

Data on 11,719 patients without a history of cancer who were enrolled in the BSRBR between 2001 and 2009 were used for the current analysis. Data after 2009 were not considered in order to allow for the lag time in cancer reporting from the U.K.’s National Cancer Registry into the Biologics Register. A group of 3,543 patients treated with nbDMARDs was used as the reference population.

Data adjustment took account of patients’ age at baseline, gender, duration of disease, use of nonsteroidal anti-inflammatory drugs, comorbidities, and age at time of enrollment in the U.K.-based register.

A total of 295 cancers were reported in patients treated with anti-TNF agents during a mean follow up of 4.6 years, giving a crude cancer rate of 63 per 10,000 patient-years. A total of 91 cancers were reported in patients treated with nbDMARDs over a median follow-up of 3.4 years, representing a crude cancer rate of 84 per 10,000 patient years.

With regard to the site of cancer, anti-TNFs appeared to be associated with a lower risk of lung cancer (aHR, 0.89; 95% CI, 0.46-1.74) and breast cancer (aHR, 0.99; 95% CI, 0.51-1.92) than were nbDMARDs. There was an increase in the risk of colorectal cancer (HR, 1.21; 95% CI, 0.54-2.70), but "the confidence intervals have become wider," Dr. Mercer observed.

Data on patients with a prior history of cancer have already been published by the team (Arthritis Care Res. 2010;62:755-63), but new data on patients with cervical carcinoma in situ (CIS) were reported during a poster presentation at the meeting (Rheumatology 2012;51:iii77, abstract 70).

Considering data collated through March 2011, 238 women had a prior history of cervical CIS – 48 of 2,654 (1.8%) women treated with nbDMARDs and 190 of 9,084 (2.1%) treated with anti-TNFs. Two women subsequently developed genitourinary cancer – both were treated with nbDMARDs. The rate of incident cancer was 13 per 1,000 person-years (95% CI, 2-45).

Dr. Mercer and her associates noted that there was a low level of reporting cervical CIS, which could reflect rheumatologists not being aware of abnormal cervical changes or choosing not to report in situ cancers or these prior cancers at baseline.

They concluded that "there were no new or recurrent female genital cancers among women with preexisting cervical CIS selected for treatment with anti-TNF," which should prove reassuring to women who may have a history of cervical abnormalities and who are considering anti-TNF therapy.

The BSRBR is funded by a grant from the British Society for Rheumatology. The BSR receives funding from Abbott Laboratories, Swedish Orphan Biovitrum (SOBI), Merck, Pfizer, Roche Products, and UCB Pharma. This income finances a separate contract between the BSR and the University of Manchester, which provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Dr. Mercer reported having no personal conflicts of interest.

GLASGOW – Biologic treatment for rheumatoid arthritis does not increase the overall risk of solid cancers beyond that of more traditional, nonbiologic drugs, according to long-awaited data from the British Society for Rheumatology Biologics Register.

At a median follow-up of almost 5 years, the adjusted hazard ratio for all solid cancers was 0.88 (95% confidence interval, 0.65-1.17) in a comparison between anti–tumor necrosis factor (anti-TNF)-alpha therapy and nonbiologic disease-modifying antirheumatic drugs (nbDMARDs, n = 3,543) in patients without a prior history of cancer.

There was no significant difference in cancer risk between the anti-TNF drugs included in the analysis, namely etanercept (adjusted hazard ratio, 0.94; 95% CI, 0.68-1.29), infliximab (aHR, 0.87; 95% CI, 0.61-1.25), and adalimumab (aHR, 0.81; 95% CI, 0.57-1.14) versus nbDMARDs. Neither duration of follow-up nor the overall site where tumors occurred had any effect on the occurrence of solid cancers.

These data lend further support to the general safety of TNF inhibitors, and add to findings reported from the British Society for Rheumatology Biologics Register (BSRBR) and other European registries, such as the Danish Biologics Registry (DANBIO), with regard to malignancy (Rheumatology News, June 2011, p. 22).

"We do still need further follow-up to address site-specific [cancer] risk and to allow for longer latency," said Dr. Louise Mercer, May 3, at the British Society for Rheumatology annual conference (Rheumatology 2012;51:iii40, abstract O37).

Dr. Mercer, a clinical research fellow at the Arthritis Research UK Epidemiology Unit, University of Manchester (England), noted that that cancer risk is already higher in patients with RA than in the general population (Rheumatology News, April 2011, p. 31). However, these latest findings from the BSRBR highlight that the use of biologic therapy doesn’t appear to add to this risk over that seen with nbDMARDs.

Data on 11,719 patients without a history of cancer who were enrolled in the BSRBR between 2001 and 2009 were used for the current analysis. Data after 2009 were not considered in order to allow for the lag time in cancer reporting from the U.K.’s National Cancer Registry into the Biologics Register. A group of 3,543 patients treated with nbDMARDs was used as the reference population.

Data adjustment took account of patients’ age at baseline, gender, duration of disease, use of nonsteroidal anti-inflammatory drugs, comorbidities, and age at time of enrollment in the U.K.-based register.

A total of 295 cancers were reported in patients treated with anti-TNF agents during a mean follow up of 4.6 years, giving a crude cancer rate of 63 per 10,000 patient-years. A total of 91 cancers were reported in patients treated with nbDMARDs over a median follow-up of 3.4 years, representing a crude cancer rate of 84 per 10,000 patient years.

With regard to the site of cancer, anti-TNFs appeared to be associated with a lower risk of lung cancer (aHR, 0.89; 95% CI, 0.46-1.74) and breast cancer (aHR, 0.99; 95% CI, 0.51-1.92) than were nbDMARDs. There was an increase in the risk of colorectal cancer (HR, 1.21; 95% CI, 0.54-2.70), but "the confidence intervals have become wider," Dr. Mercer observed.

Data on patients with a prior history of cancer have already been published by the team (Arthritis Care Res. 2010;62:755-63), but new data on patients with cervical carcinoma in situ (CIS) were reported during a poster presentation at the meeting (Rheumatology 2012;51:iii77, abstract 70).

Considering data collated through March 2011, 238 women had a prior history of cervical CIS – 48 of 2,654 (1.8%) women treated with nbDMARDs and 190 of 9,084 (2.1%) treated with anti-TNFs. Two women subsequently developed genitourinary cancer – both were treated with nbDMARDs. The rate of incident cancer was 13 per 1,000 person-years (95% CI, 2-45).

Dr. Mercer and her associates noted that there was a low level of reporting cervical CIS, which could reflect rheumatologists not being aware of abnormal cervical changes or choosing not to report in situ cancers or these prior cancers at baseline.

They concluded that "there were no new or recurrent female genital cancers among women with preexisting cervical CIS selected for treatment with anti-TNF," which should prove reassuring to women who may have a history of cervical abnormalities and who are considering anti-TNF therapy.

The BSRBR is funded by a grant from the British Society for Rheumatology. The BSR receives funding from Abbott Laboratories, Swedish Orphan Biovitrum (SOBI), Merck, Pfizer, Roche Products, and UCB Pharma. This income finances a separate contract between the BSR and the University of Manchester, which provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Dr. Mercer reported having no personal conflicts of interest.

SILVER SPRING, MD. – There soon may be a new oral disease-modifying antirheumatic drug in town, the first in more than 10 years to be approved for the treatment of rheumatoid arthritis.

The drug is tofacitinib, and it is the first in a new class of agents for RA patients.

On May 9 the Food and Drug Administration’s Arthritis Advisory Committee voted 8 to 2 in favor of approving tofacitinib for RA patients who have had inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs).

A small-molecule inhibitor of the Janus kinase (JAK) pathways, Pfizer’s tofacitinib blocks inflammatory cytokines that play a role in the pathogenesis of RA. If approved, tofacitinib would be the first JAK inhibitor for RA. Another JAK inhibitor, ruxolitinib (Incyte’s Jakafi) was approved to treat myelofibrosis in November.

Pfizer’s application was based on five randomized controlled phase III efficacy trials involving a total 3,315 patients. The application also included safety data for a total of 4,816 patients from the phase II and III studies, of whom 4,053 were treated for at least 6 months and 567 for more than 3 years, up to 42 months. Among the trials was one that compared tofacitinib with placebo in patients with moderate to severe RA who had incomplete responses to tumor necrosis factor (TNF) inhibitors, and four studies of patients who had inadequate responses to other DMARDs. One study included an arm with adalimumab as an active comparator, and one evaluated radiographic response. In three studies, the participants were taking background methotrexate, and in one study, tofacitinib was used as monotherapy. The studies were conducted in a total of 44 countries.

All five of the phase III studies were designed to show the superiority of 5-mg and 10-mg twice-daily doses of tofacitinib to placebo for the primary end points: a 20% or better increase in the American College of Rheumatology’s definition of improvement in the signs and symptoms of RA (ACR20), improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and a Disease Activity Score-28 (DAS28) of less than 2.6. In most of the assessments conducted at 6 and 12 months, both doses exhibited statistical superiority over placebo, with the 10-mg dose showing greater improvement than the 5-mg dose.

However, the fact that only one study evaluated radiographic evidence, which the FDA reviewers deemed inconclusive, was cause for concern for the FDA reviewers and committee members. According to the FDA’s Dr. Yongman Kim, 18% of the 278 patients on 5 mg of tofacitinib, 16% of the 290 with 10 mg of tofacitinib, and 14% of the 140 placebo patients showed an "improved" modified total sharp score (mTSS) of less than 0, suggesting it inhibited joint damage.

The FDA was also concerned about dose- and time-dependent elevations in malignancies, and particularly lymphomas, with a standardized incidence ratio of 2.35 at a median 9 months duration of exposure. Of the seven total patients who developed lymphoma, three were on 5 mg of tofacitinib, three were on 10 mg, and one was in a still-blinded arm of the trial. Overall malignancy rates increased with time, from 0.79 per 100 patient-years at 0-6 months to 1.06 at 12-18 months to 1.43 beyond 24 months.

Several of the committee members who voted in favor of tofacitinib said that they did so because they wanted a new oral option for RA patients and that they don’t anticipate any better data from clinical trials. They strongly urged postmarketing studies of both radiologic efficacy and safety. Pfizer has proposed a Risk Evaluation and Mitigation Strategy that will include, alongside labeling provisions, a Medication Guide, a "Dear Health Care Professional" letter, and routine pharmacovigilance. Additional clinical studies that are ongoing or planned include long-term extension studies to assess cardiovascular safety, serious and opportunistic infections, malignancies, and gastrointestinal perforations; studies to monitor any unidentified risks; a cholesterol kinetic study; and studies to evaluate the effect of tofacitinib on the immune response to pneumococcal and influenza vaccines as well as to further delineate the effects of tofacitinib on lymphocyte subsets.

The panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver but not at this meeting.

Martin Bermin-Gorvine of "The Pink Sheet" contributed to this story. This news service and "The Pink Sheet" are both owned by Elsevier.

SILVER SPRING, MD. – There soon may be a new oral disease-modifying antirheumatic drug in town, the first in more than 10 years to be approved for the treatment of rheumatoid arthritis.

The drug is tofacitinib, and it is the first in a new class of agents for RA patients.

On May 9 the Food and Drug Administration’s Arthritis Advisory Committee voted 8 to 2 in favor of approving tofacitinib for RA patients who have had inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs).

A small-molecule inhibitor of the Janus kinase (JAK) pathways, Pfizer’s tofacitinib blocks inflammatory cytokines that play a role in the pathogenesis of RA. If approved, tofacitinib would be the first JAK inhibitor for RA. Another JAK inhibitor, ruxolitinib (Incyte’s Jakafi) was approved to treat myelofibrosis in November.

Pfizer’s application was based on five randomized controlled phase III efficacy trials involving a total 3,315 patients. The application also included safety data for a total of 4,816 patients from the phase II and III studies, of whom 4,053 were treated for at least 6 months and 567 for more than 3 years, up to 42 months. Among the trials was one that compared tofacitinib with placebo in patients with moderate to severe RA who had incomplete responses to tumor necrosis factor (TNF) inhibitors, and four studies of patients who had inadequate responses to other DMARDs. One study included an arm with adalimumab as an active comparator, and one evaluated radiographic response. In three studies, the participants were taking background methotrexate, and in one study, tofacitinib was used as monotherapy. The studies were conducted in a total of 44 countries.

All five of the phase III studies were designed to show the superiority of 5-mg and 10-mg twice-daily doses of tofacitinib to placebo for the primary end points: a 20% or better increase in the American College of Rheumatology’s definition of improvement in the signs and symptoms of RA (ACR20), improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and a Disease Activity Score-28 (DAS28) of less than 2.6. In most of the assessments conducted at 6 and 12 months, both doses exhibited statistical superiority over placebo, with the 10-mg dose showing greater improvement than the 5-mg dose.

However, the fact that only one study evaluated radiographic evidence, which the FDA reviewers deemed inconclusive, was cause for concern for the FDA reviewers and committee members. According to the FDA’s Dr. Yongman Kim, 18% of the 278 patients on 5 mg of tofacitinib, 16% of the 290 with 10 mg of tofacitinib, and 14% of the 140 placebo patients showed an "improved" modified total sharp score (mTSS) of less than 0, suggesting it inhibited joint damage.

The FDA was also concerned about dose- and time-dependent elevations in malignancies, and particularly lymphomas, with a standardized incidence ratio of 2.35 at a median 9 months duration of exposure. Of the seven total patients who developed lymphoma, three were on 5 mg of tofacitinib, three were on 10 mg, and one was in a still-blinded arm of the trial. Overall malignancy rates increased with time, from 0.79 per 100 patient-years at 0-6 months to 1.06 at 12-18 months to 1.43 beyond 24 months.

Several of the committee members who voted in favor of tofacitinib said that they did so because they wanted a new oral option for RA patients and that they don’t anticipate any better data from clinical trials. They strongly urged postmarketing studies of both radiologic efficacy and safety. Pfizer has proposed a Risk Evaluation and Mitigation Strategy that will include, alongside labeling provisions, a Medication Guide, a "Dear Health Care Professional" letter, and routine pharmacovigilance. Additional clinical studies that are ongoing or planned include long-term extension studies to assess cardiovascular safety, serious and opportunistic infections, malignancies, and gastrointestinal perforations; studies to monitor any unidentified risks; a cholesterol kinetic study; and studies to evaluate the effect of tofacitinib on the immune response to pneumococcal and influenza vaccines as well as to further delineate the effects of tofacitinib on lymphocyte subsets.

The panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver but not at this meeting.

Martin Bermin-Gorvine of "The Pink Sheet" contributed to this story. This news service and "The Pink Sheet" are both owned by Elsevier.

SILVER SPRING, MD. – There soon may be a new oral disease-modifying antirheumatic drug in town, the first in more than 10 years to be approved for the treatment of rheumatoid arthritis.

The drug is tofacitinib, and it is the first in a new class of agents for RA patients.

On May 9 the Food and Drug Administration’s Arthritis Advisory Committee voted 8 to 2 in favor of approving tofacitinib for RA patients who have had inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs).

A small-molecule inhibitor of the Janus kinase (JAK) pathways, Pfizer’s tofacitinib blocks inflammatory cytokines that play a role in the pathogenesis of RA. If approved, tofacitinib would be the first JAK inhibitor for RA. Another JAK inhibitor, ruxolitinib (Incyte’s Jakafi) was approved to treat myelofibrosis in November.

Pfizer’s application was based on five randomized controlled phase III efficacy trials involving a total 3,315 patients. The application also included safety data for a total of 4,816 patients from the phase II and III studies, of whom 4,053 were treated for at least 6 months and 567 for more than 3 years, up to 42 months. Among the trials was one that compared tofacitinib with placebo in patients with moderate to severe RA who had incomplete responses to tumor necrosis factor (TNF) inhibitors, and four studies of patients who had inadequate responses to other DMARDs. One study included an arm with adalimumab as an active comparator, and one evaluated radiographic response. In three studies, the participants were taking background methotrexate, and in one study, tofacitinib was used as monotherapy. The studies were conducted in a total of 44 countries.

All five of the phase III studies were designed to show the superiority of 5-mg and 10-mg twice-daily doses of tofacitinib to placebo for the primary end points: a 20% or better increase in the American College of Rheumatology’s definition of improvement in the signs and symptoms of RA (ACR20), improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and a Disease Activity Score-28 (DAS28) of less than 2.6. In most of the assessments conducted at 6 and 12 months, both doses exhibited statistical superiority over placebo, with the 10-mg dose showing greater improvement than the 5-mg dose.

However, the fact that only one study evaluated radiographic evidence, which the FDA reviewers deemed inconclusive, was cause for concern for the FDA reviewers and committee members. According to the FDA’s Dr. Yongman Kim, 18% of the 278 patients on 5 mg of tofacitinib, 16% of the 290 with 10 mg of tofacitinib, and 14% of the 140 placebo patients showed an "improved" modified total sharp score (mTSS) of less than 0, suggesting it inhibited joint damage.

The FDA was also concerned about dose- and time-dependent elevations in malignancies, and particularly lymphomas, with a standardized incidence ratio of 2.35 at a median 9 months duration of exposure. Of the seven total patients who developed lymphoma, three were on 5 mg of tofacitinib, three were on 10 mg, and one was in a still-blinded arm of the trial. Overall malignancy rates increased with time, from 0.79 per 100 patient-years at 0-6 months to 1.06 at 12-18 months to 1.43 beyond 24 months.

Several of the committee members who voted in favor of tofacitinib said that they did so because they wanted a new oral option for RA patients and that they don’t anticipate any better data from clinical trials. They strongly urged postmarketing studies of both radiologic efficacy and safety. Pfizer has proposed a Risk Evaluation and Mitigation Strategy that will include, alongside labeling provisions, a Medication Guide, a "Dear Health Care Professional" letter, and routine pharmacovigilance. Additional clinical studies that are ongoing or planned include long-term extension studies to assess cardiovascular safety, serious and opportunistic infections, malignancies, and gastrointestinal perforations; studies to monitor any unidentified risks; a cholesterol kinetic study; and studies to evaluate the effect of tofacitinib on the immune response to pneumococcal and influenza vaccines as well as to further delineate the effects of tofacitinib on lymphocyte subsets.

The panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver but not at this meeting.

Martin Bermin-Gorvine of "The Pink Sheet" contributed to this story. This news service and "The Pink Sheet" are both owned by Elsevier.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

In this month's program, Dr. Craig Leonardi opines on how two investigational monoclonal antibody therapies may stack up against the competition for treating psoriasis.

Then, Dr. Cheryl Gustafson discusses what drugs are most often to blame for cutaneous reactions that lead to ambulatory visits.

Cosmetic counter host Dr. Lily Talakoub offers tips on how to choose the right EHR for your practice.

And finally, Dr. Alan Rockoff tells the tale of how he helped a patient win a bikini contest.

In this month's program, Dr. Craig Leonardi opines on how two investigational monoclonal antibody therapies may stack up against the competition for treating psoriasis.

Then, Dr. Cheryl Gustafson discusses what drugs are most often to blame for cutaneous reactions that lead to ambulatory visits.

Cosmetic counter host Dr. Lily Talakoub offers tips on how to choose the right EHR for your practice.

And finally, Dr. Alan Rockoff tells the tale of how he helped a patient win a bikini contest.

In this month's program, Dr. Craig Leonardi opines on how two investigational monoclonal antibody therapies may stack up against the competition for treating psoriasis.

Then, Dr. Cheryl Gustafson discusses what drugs are most often to blame for cutaneous reactions that lead to ambulatory visits.

Cosmetic counter host Dr. Lily Talakoub offers tips on how to choose the right EHR for your practice.

And finally, Dr. Alan Rockoff tells the tale of how he helped a patient win a bikini contest.

SAN DIEGO – When psoriasis patients present to Dr. Abrar A. Qureshi with concomitant pain or stiffness, he routinely asks, "What is your worst time of day?"

"If patients say they experience an hour or more of profound morning stiffness, think inflammatory arthritis," Dr. Qureshi said at the annual meeting of the American Academy of Dermatology. "Some patients will be stiff in the morning for 5-15 minutes. That’s more suggestive of osteoarthritis, though there is no hard and fast rule."

Dr. Qureshi of the department of dermatology at Brigham and Women’s Hospital, Boston, also asks patients about joint swelling and if they have trouble getting into a car. His recommended physical exam consists of vitals, weight, height, nail changes, inverse psoriasis, swollen joints, warm joints, "sausage" digits, and the Schober test. "We do see patients with fatigue and malaise, occasionally low grade fever, and we always ask about TB exposure," he said.

He emphasized that dermatologists "are on the front line in the care of these patients. It behooves us to think about psoriatic arthritis, because the numbers suggest that 20%-25% of patients with psoriasis may develop psoriatic arthritis. If the diagnosis is missed, this can lead to debilitating pain, permanent joint damage, and disability."

If a psoriasis patient presents with pain or stiffness, consider inflammatory arthritis, including dactylitis and spondyloarthropathy, Dr. Qureshi said. Other differential diagnoses to consider include noninflammatory arthritis (osteoarthritis) or soft tissue problems such as enthesitis. "Osteoarthritis is probably the biggest red herring for dermatologists," he said.

In a study of patients referred by rheumatologists to the department of dermatology at Brigham and Women’s Hospital, the three most common diagnoses made by the rheumatologists prior to referral were psoriatic arthritis (41%), osteoarthritis (27%), and psoriatic arthritis plus osteoarthritis (15%).

Dr. Qureshi said that he had no relevant financial conflicts to disclose.

SAN DIEGO – When psoriasis patients present to Dr. Abrar A. Qureshi with concomitant pain or stiffness, he routinely asks, "What is your worst time of day?"

"If patients say they experience an hour or more of profound morning stiffness, think inflammatory arthritis," Dr. Qureshi said at the annual meeting of the American Academy of Dermatology. "Some patients will be stiff in the morning for 5-15 minutes. That’s more suggestive of osteoarthritis, though there is no hard and fast rule."

Dr. Qureshi of the department of dermatology at Brigham and Women’s Hospital, Boston, also asks patients about joint swelling and if they have trouble getting into a car. His recommended physical exam consists of vitals, weight, height, nail changes, inverse psoriasis, swollen joints, warm joints, "sausage" digits, and the Schober test. "We do see patients with fatigue and malaise, occasionally low grade fever, and we always ask about TB exposure," he said.

He emphasized that dermatologists "are on the front line in the care of these patients. It behooves us to think about psoriatic arthritis, because the numbers suggest that 20%-25% of patients with psoriasis may develop psoriatic arthritis. If the diagnosis is missed, this can lead to debilitating pain, permanent joint damage, and disability."

If a psoriasis patient presents with pain or stiffness, consider inflammatory arthritis, including dactylitis and spondyloarthropathy, Dr. Qureshi said. Other differential diagnoses to consider include noninflammatory arthritis (osteoarthritis) or soft tissue problems such as enthesitis. "Osteoarthritis is probably the biggest red herring for dermatologists," he said.

In a study of patients referred by rheumatologists to the department of dermatology at Brigham and Women’s Hospital, the three most common diagnoses made by the rheumatologists prior to referral were psoriatic arthritis (41%), osteoarthritis (27%), and psoriatic arthritis plus osteoarthritis (15%).

Dr. Qureshi said that he had no relevant financial conflicts to disclose.

SAN DIEGO – When psoriasis patients present to Dr. Abrar A. Qureshi with concomitant pain or stiffness, he routinely asks, "What is your worst time of day?"

"If patients say they experience an hour or more of profound morning stiffness, think inflammatory arthritis," Dr. Qureshi said at the annual meeting of the American Academy of Dermatology. "Some patients will be stiff in the morning for 5-15 minutes. That’s more suggestive of osteoarthritis, though there is no hard and fast rule."

Dr. Qureshi of the department of dermatology at Brigham and Women’s Hospital, Boston, also asks patients about joint swelling and if they have trouble getting into a car. His recommended physical exam consists of vitals, weight, height, nail changes, inverse psoriasis, swollen joints, warm joints, "sausage" digits, and the Schober test. "We do see patients with fatigue and malaise, occasionally low grade fever, and we always ask about TB exposure," he said.

He emphasized that dermatologists "are on the front line in the care of these patients. It behooves us to think about psoriatic arthritis, because the numbers suggest that 20%-25% of patients with psoriasis may develop psoriatic arthritis. If the diagnosis is missed, this can lead to debilitating pain, permanent joint damage, and disability."

If a psoriasis patient presents with pain or stiffness, consider inflammatory arthritis, including dactylitis and spondyloarthropathy, Dr. Qureshi said. Other differential diagnoses to consider include noninflammatory arthritis (osteoarthritis) or soft tissue problems such as enthesitis. "Osteoarthritis is probably the biggest red herring for dermatologists," he said.

In a study of patients referred by rheumatologists to the department of dermatology at Brigham and Women’s Hospital, the three most common diagnoses made by the rheumatologists prior to referral were psoriatic arthritis (41%), osteoarthritis (27%), and psoriatic arthritis plus osteoarthritis (15%).

Dr. Qureshi said that he had no relevant financial conflicts to disclose.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

Patients with rheumatic disease who take anti-tumor necrosis factor drugs are four times more likely to develop mycobacterial diseases than patients not taking the drugs, and up to 14 times more likely to die from those diseases.

Anti-TNF drugs were associated with significantly increased risks for tuberculosis and nontuberculous mycobacterial disease, Dr. Kevin Winthrop and colleagues reported in the April 20 online edition of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012 April 20 [doi:10.1136/annrheumdis-2011-200690]). Because most of the deaths in their retrospective study occurred in patients with nontubercular mycobacterial (NTM) disease, physicians should consider anti-TNF agents carefully in such patients, they said.

"It is currently unclear if patients with active NTM disease can safely receive anti-TNF therapy," wrote Dr. Winthrop of the Oregon Health and Science University, Portland, and his coauthors. "These cases [in this study] and the reports of others, suggest patients with NTM disease should discontinue anti-TNF therapy."

The investigators extracted their data from a large health care database, identifying 8,418 patients who took anti-TNF medications from 2000-2008. Most of these subjects had a diagnosis of rheumatoid arthritis (61%); 64% were female and 61% white.

There were 16 cases of tuberculosis and 18 cases of NTM that developed after the initiation of therapy. Among the TB cases, 69% (11) were pulmonary and 25% (4) extrapulmonary. Disease location was unknown in one patient. Rheumatoid arthritis was the most common diagnosis in this group (75%; 12 patients); one patient had Crohn’s disease, one had ulcerative colitis, and three had psoriasis. Their median age was 57 years.

Tuberculosis developed a median of 670 days after beginning the drug, but the time of onset varied widely (1-3,181 days). At the time of diagnosis, nine (44%) were taking prednisone and four (25%) were taking methotrexate; most (63%) were taking anti-TNF drugs.

Three patients (19%) died during the study period, with a median time of 74 days between disease onset and death.

Of the NTM cases, 67% (12) were pulmonary and four (22%) extrapulmonary; disease location was unknown in two patients. All of the patents had rheumatoid arthritis. Three (15%) also had psoriasis and two (11%) ankylosing spondylitis. Their median age was 68 years.

The median onset of disease was 1,027 days after beginning therapy (range 77-2,832). At the time of diagnosis nine (50%) were taking prednisone and two (11%) were taking methotrexate; most (83%) were also taking anti-TNF drugs.

Seven of this group (39%) died during the study period, with a median time of 569 days (range 21-2,127 days) between disease onset and death.

Both tuberculosis and NTM were more common in anti-TNF exposed patients than in the general population. In exposed patients, the investigators calculated a rate of 105 NTM cases and 56 tuberculosis cases per 100,000 persons per year, compared to 3 and 4 per 100,000 respectively in the general population. Incidence of both diseases was highest among those taking monoclonal antibodies (123 tuberculosis and 168 NTM cases per 100,000). Etanercept was associated with the lowest incidence – 17 tuberculosis and 35 NTM cases per 100,000.

Compared to non-infected anti-TNF users, those with tuberculosis were less likely to be white and significantly more likely to have diabetes or chronic renal disease. Those with NTM were significantly older, and more likely to be white, have gastroesophageal reflux disease, or chronic lung disease.

All of those with NTM had a diagnosis of rheumatoid arthritis, compared to 60% of uninfected anti-TNF users. NTM patients were four times more likely to have used infliximab than the uninfected group (67% vs. 33%; odds ratio, 4.0).

The investigators also stratified findings by age. In an analysis of patients 50 years and older, they found a significant association between NTM and a rheumatoid arthritis diagnosis. "All seven of the observed NTM case deaths were in this group," they noted. "NTM disease rates were substantially higher in this ... subset."

The finding of more NTM than tuberculosis cases is "not surprising," the authors wrote, "Given the low prevalence of tuberculosis in the U.S. and given that tuberculosis screening guidelines have been well-publicized in the last 5 years, making it likely that tuberculosis cases were averted in our study population."

Nevertheless, the study highlights the importance of identifying risk factors for both diseases in patients taking anti-TNF medications.

"These include chronic renal disease and diabetes mellitus for tuberculosis and chronic lung disease for NTM. These associations are important for physicians to recognize when considering anti-TNF therapy use."

The study was funded by a grant from UCB Pharmaceuticals. Dr. Winthrop has received grant money from the company as advisory board remuneration from Amgen, Genentech, and Oxford Immunotec. Coauthors also reported a number of disclosures, including links to UCB.

Patients with rheumatic disease who take anti-tumor necrosis factor drugs are four times more likely to develop mycobacterial diseases than patients not taking the drugs, and up to 14 times more likely to die from those diseases.

Anti-TNF drugs were associated with significantly increased risks for tuberculosis and nontuberculous mycobacterial disease, Dr. Kevin Winthrop and colleagues reported in the April 20 online edition of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012 April 20 [doi:10.1136/annrheumdis-2011-200690]). Because most of the deaths in their retrospective study occurred in patients with nontubercular mycobacterial (NTM) disease, physicians should consider anti-TNF agents carefully in such patients, they said.

"It is currently unclear if patients with active NTM disease can safely receive anti-TNF therapy," wrote Dr. Winthrop of the Oregon Health and Science University, Portland, and his coauthors. "These cases [in this study] and the reports of others, suggest patients with NTM disease should discontinue anti-TNF therapy."

The investigators extracted their data from a large health care database, identifying 8,418 patients who took anti-TNF medications from 2000-2008. Most of these subjects had a diagnosis of rheumatoid arthritis (61%); 64% were female and 61% white.

There were 16 cases of tuberculosis and 18 cases of NTM that developed after the initiation of therapy. Among the TB cases, 69% (11) were pulmonary and 25% (4) extrapulmonary. Disease location was unknown in one patient. Rheumatoid arthritis was the most common diagnosis in this group (75%; 12 patients); one patient had Crohn’s disease, one had ulcerative colitis, and three had psoriasis. Their median age was 57 years.

Tuberculosis developed a median of 670 days after beginning the drug, but the time of onset varied widely (1-3,181 days). At the time of diagnosis, nine (44%) were taking prednisone and four (25%) were taking methotrexate; most (63%) were taking anti-TNF drugs.

Three patients (19%) died during the study period, with a median time of 74 days between disease onset and death.

Of the NTM cases, 67% (12) were pulmonary and four (22%) extrapulmonary; disease location was unknown in two patients. All of the patents had rheumatoid arthritis. Three (15%) also had psoriasis and two (11%) ankylosing spondylitis. Their median age was 68 years.

The median onset of disease was 1,027 days after beginning therapy (range 77-2,832). At the time of diagnosis nine (50%) were taking prednisone and two (11%) were taking methotrexate; most (83%) were also taking anti-TNF drugs.

Seven of this group (39%) died during the study period, with a median time of 569 days (range 21-2,127 days) between disease onset and death.

Both tuberculosis and NTM were more common in anti-TNF exposed patients than in the general population. In exposed patients, the investigators calculated a rate of 105 NTM cases and 56 tuberculosis cases per 100,000 persons per year, compared to 3 and 4 per 100,000 respectively in the general population. Incidence of both diseases was highest among those taking monoclonal antibodies (123 tuberculosis and 168 NTM cases per 100,000). Etanercept was associated with the lowest incidence – 17 tuberculosis and 35 NTM cases per 100,000.

Compared to non-infected anti-TNF users, those with tuberculosis were less likely to be white and significantly more likely to have diabetes or chronic renal disease. Those with NTM were significantly older, and more likely to be white, have gastroesophageal reflux disease, or chronic lung disease.

All of those with NTM had a diagnosis of rheumatoid arthritis, compared to 60% of uninfected anti-TNF users. NTM patients were four times more likely to have used infliximab than the uninfected group (67% vs. 33%; odds ratio, 4.0).

The investigators also stratified findings by age. In an analysis of patients 50 years and older, they found a significant association between NTM and a rheumatoid arthritis diagnosis. "All seven of the observed NTM case deaths were in this group," they noted. "NTM disease rates were substantially higher in this ... subset."

The finding of more NTM than tuberculosis cases is "not surprising," the authors wrote, "Given the low prevalence of tuberculosis in the U.S. and given that tuberculosis screening guidelines have been well-publicized in the last 5 years, making it likely that tuberculosis cases were averted in our study population."

Nevertheless, the study highlights the importance of identifying risk factors for both diseases in patients taking anti-TNF medications.

"These include chronic renal disease and diabetes mellitus for tuberculosis and chronic lung disease for NTM. These associations are important for physicians to recognize when considering anti-TNF therapy use."

The study was funded by a grant from UCB Pharmaceuticals. Dr. Winthrop has received grant money from the company as advisory board remuneration from Amgen, Genentech, and Oxford Immunotec. Coauthors also reported a number of disclosures, including links to UCB.

Patients with rheumatic disease who take anti-tumor necrosis factor drugs are four times more likely to develop mycobacterial diseases than patients not taking the drugs, and up to 14 times more likely to die from those diseases.

Anti-TNF drugs were associated with significantly increased risks for tuberculosis and nontuberculous mycobacterial disease, Dr. Kevin Winthrop and colleagues reported in the April 20 online edition of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012 April 20 [doi:10.1136/annrheumdis-2011-200690]). Because most of the deaths in their retrospective study occurred in patients with nontubercular mycobacterial (NTM) disease, physicians should consider anti-TNF agents carefully in such patients, they said.

"It is currently unclear if patients with active NTM disease can safely receive anti-TNF therapy," wrote Dr. Winthrop of the Oregon Health and Science University, Portland, and his coauthors. "These cases [in this study] and the reports of others, suggest patients with NTM disease should discontinue anti-TNF therapy."

The investigators extracted their data from a large health care database, identifying 8,418 patients who took anti-TNF medications from 2000-2008. Most of these subjects had a diagnosis of rheumatoid arthritis (61%); 64% were female and 61% white.

There were 16 cases of tuberculosis and 18 cases of NTM that developed after the initiation of therapy. Among the TB cases, 69% (11) were pulmonary and 25% (4) extrapulmonary. Disease location was unknown in one patient. Rheumatoid arthritis was the most common diagnosis in this group (75%; 12 patients); one patient had Crohn’s disease, one had ulcerative colitis, and three had psoriasis. Their median age was 57 years.

Tuberculosis developed a median of 670 days after beginning the drug, but the time of onset varied widely (1-3,181 days). At the time of diagnosis, nine (44%) were taking prednisone and four (25%) were taking methotrexate; most (63%) were taking anti-TNF drugs.

Three patients (19%) died during the study period, with a median time of 74 days between disease onset and death.

Of the NTM cases, 67% (12) were pulmonary and four (22%) extrapulmonary; disease location was unknown in two patients. All of the patents had rheumatoid arthritis. Three (15%) also had psoriasis and two (11%) ankylosing spondylitis. Their median age was 68 years.

The median onset of disease was 1,027 days after beginning therapy (range 77-2,832). At the time of diagnosis nine (50%) were taking prednisone and two (11%) were taking methotrexate; most (83%) were also taking anti-TNF drugs.

Seven of this group (39%) died during the study period, with a median time of 569 days (range 21-2,127 days) between disease onset and death.

Both tuberculosis and NTM were more common in anti-TNF exposed patients than in the general population. In exposed patients, the investigators calculated a rate of 105 NTM cases and 56 tuberculosis cases per 100,000 persons per year, compared to 3 and 4 per 100,000 respectively in the general population. Incidence of both diseases was highest among those taking monoclonal antibodies (123 tuberculosis and 168 NTM cases per 100,000). Etanercept was associated with the lowest incidence – 17 tuberculosis and 35 NTM cases per 100,000.

Compared to non-infected anti-TNF users, those with tuberculosis were less likely to be white and significantly more likely to have diabetes or chronic renal disease. Those with NTM were significantly older, and more likely to be white, have gastroesophageal reflux disease, or chronic lung disease.

All of those with NTM had a diagnosis of rheumatoid arthritis, compared to 60% of uninfected anti-TNF users. NTM patients were four times more likely to have used infliximab than the uninfected group (67% vs. 33%; odds ratio, 4.0).

The investigators also stratified findings by age. In an analysis of patients 50 years and older, they found a significant association between NTM and a rheumatoid arthritis diagnosis. "All seven of the observed NTM case deaths were in this group," they noted. "NTM disease rates were substantially higher in this ... subset."

The finding of more NTM than tuberculosis cases is "not surprising," the authors wrote, "Given the low prevalence of tuberculosis in the U.S. and given that tuberculosis screening guidelines have been well-publicized in the last 5 years, making it likely that tuberculosis cases were averted in our study population."

Nevertheless, the study highlights the importance of identifying risk factors for both diseases in patients taking anti-TNF medications.

"These include chronic renal disease and diabetes mellitus for tuberculosis and chronic lung disease for NTM. These associations are important for physicians to recognize when considering anti-TNF therapy use."

The study was funded by a grant from UCB Pharmaceuticals. Dr. Winthrop has received grant money from the company as advisory board remuneration from Amgen, Genentech, and Oxford Immunotec. Coauthors also reported a number of disclosures, including links to UCB.

VICTORIA, B.C. – Some patients with systemic lupus erythematosus may be more likely than others to experience a prolonged remission, new data suggest.

In a study of more than 1,500 patients who had SLE, about 2% achieved a remission lasting at least 5 years on either no medication or only antimalarial drugs, Anjali Papneja reported at the annual meeting of the Canadian Rheumatology Association.

The prolonged remissions lasted on average almost 12 years. Nearly a third of the patients had had a monophasic clinical disease course, characterized by only a single flare, before their remission.

Patients achieving a prolonged remission were more likely to be white, had milder disease, and were less likely to have involvement of certain organ systems and to have received steroids or other immunosuppressive agents prior to remission onset.

"Prolonged remission is an infrequent outcome among SLE patients, but it generally lasts for over a decade, and it is preceded by an atypically monophasic clinical course in a significant minority," Ms. Papneja commented.

"We want to know what makes these patients different, how they can be treated most effectively, and how we can harness this unique and desirable outcome more generally," she added.

An attendee asked what the remission rate was if patients who achieved remission on stable immunosuppressive regimens and/or low-dose prednisone were also included.

The reason for including only those patients who had remitted off all steroids and immunosuppressive agents was to distinguish those whose SLE was in true remission (i.e., those in the cohort), from those whose disease was merely suppressed by the ongoing use of these medications, replied Ms. Papneja, a medical student at the University of Toronto. "But they do remain on antimalarials because in recent decades, it has been found that these patients have cardiovascular protective benefits from antimalarials."

The investigators studied all patients with SLE followed at the university’s Lupus Clinic from July 1970 through May 2011.

Patients were defined as having a prolonged remission if they did not have any clinical disease activity for at least 5 years, had regular clinic visits, and received no immunosuppressive medications or at most antimalarial drugs during the remission.

With a mean duration of follow-up of nearly 22 years, 2.4% of the 1,613 patients studied achieved a prolonged remission, after a mean disease duration of about 9 years. These sustained remissions lasted an average of nearly 12 years.

By type, 44% of the remissions were serologically and clinically quiescent, 28% were serologically active but clinically quiescent, and 28% fluctuated between these types.

In the years leading up to the remission, the majority of patients (71%) had a relapsing-remitting clinical course, but a sizable proportion (29%) had a monophasic course. "It’s worthwhile to study these patients further to determine at what point we can safely define a disease course as being monophasic," Ms. Papneja commented. None of the patients achieving prolonged remission had a chronic active course.

In a case-control comparison, in which each patient who achieved prolonged remission was matched with three who did not, the former were more likely to be white (82% vs. 72%), had a lower SLE Disease Activity Index (SLEDAI-2K) score at their first clinic visit (8 vs. 10.6), and had a lower adjusted mean SLEDAI-2K score in the 3 years leading up to remission (3 vs. 5.9).

The group achieving prolonged remission was also significantly less likely to have skin, pulmonary, and central nervous system involvement, but "we noted that there was no difference in renal involvement between cases and controls," she pointed out. Additionally, they were less likely to have received steroids (58% vs. 80%) and other immunosuppressive agents (24% vs. 47%) prior to remission onset, also seeming to point to milder disease.

A study limitation, Ms. Papneja acknowledged, was that only patients continuing care at the clinic were included, and the clinic’s attrition rate was about 10%. Thus, some patients achieving remission and dropping out of care, or having a flare and seeking treatment elsewhere, may have been lost to follow-up.

Ms. Papneja disclosed that she had no relevant conflicts of interest.

VICTORIA, B.C. – Some patients with systemic lupus erythematosus may be more likely than others to experience a prolonged remission, new data suggest.

In a study of more than 1,500 patients who had SLE, about 2% achieved a remission lasting at least 5 years on either no medication or only antimalarial drugs, Anjali Papneja reported at the annual meeting of the Canadian Rheumatology Association.

The prolonged remissions lasted on average almost 12 years. Nearly a third of the patients had had a monophasic clinical disease course, characterized by only a single flare, before their remission.

Patients achieving a prolonged remission were more likely to be white, had milder disease, and were less likely to have involvement of certain organ systems and to have received steroids or other immunosuppressive agents prior to remission onset.

"Prolonged remission is an infrequent outcome among SLE patients, but it generally lasts for over a decade, and it is preceded by an atypically monophasic clinical course in a significant minority," Ms. Papneja commented.

"We want to know what makes these patients different, how they can be treated most effectively, and how we can harness this unique and desirable outcome more generally," she added.

An attendee asked what the remission rate was if patients who achieved remission on stable immunosuppressive regimens and/or low-dose prednisone were also included.

The reason for including only those patients who had remitted off all steroids and immunosuppressive agents was to distinguish those whose SLE was in true remission (i.e., those in the cohort), from those whose disease was merely suppressed by the ongoing use of these medications, replied Ms. Papneja, a medical student at the University of Toronto. "But they do remain on antimalarials because in recent decades, it has been found that these patients have cardiovascular protective benefits from antimalarials."

The investigators studied all patients with SLE followed at the university’s Lupus Clinic from July 1970 through May 2011.

Patients were defined as having a prolonged remission if they did not have any clinical disease activity for at least 5 years, had regular clinic visits, and received no immunosuppressive medications or at most antimalarial drugs during the remission.

With a mean duration of follow-up of nearly 22 years, 2.4% of the 1,613 patients studied achieved a prolonged remission, after a mean disease duration of about 9 years. These sustained remissions lasted an average of nearly 12 years.

By type, 44% of the remissions were serologically and clinically quiescent, 28% were serologically active but clinically quiescent, and 28% fluctuated between these types.

In the years leading up to the remission, the majority of patients (71%) had a relapsing-remitting clinical course, but a sizable proportion (29%) had a monophasic course. "It’s worthwhile to study these patients further to determine at what point we can safely define a disease course as being monophasic," Ms. Papneja commented. None of the patients achieving prolonged remission had a chronic active course.

In a case-control comparison, in which each patient who achieved prolonged remission was matched with three who did not, the former were more likely to be white (82% vs. 72%), had a lower SLE Disease Activity Index (SLEDAI-2K) score at their first clinic visit (8 vs. 10.6), and had a lower adjusted mean SLEDAI-2K score in the 3 years leading up to remission (3 vs. 5.9).

The group achieving prolonged remission was also significantly less likely to have skin, pulmonary, and central nervous system involvement, but "we noted that there was no difference in renal involvement between cases and controls," she pointed out. Additionally, they were less likely to have received steroids (58% vs. 80%) and other immunosuppressive agents (24% vs. 47%) prior to remission onset, also seeming to point to milder disease.

A study limitation, Ms. Papneja acknowledged, was that only patients continuing care at the clinic were included, and the clinic’s attrition rate was about 10%. Thus, some patients achieving remission and dropping out of care, or having a flare and seeking treatment elsewhere, may have been lost to follow-up.

Ms. Papneja disclosed that she had no relevant conflicts of interest.

VICTORIA, B.C. – Some patients with systemic lupus erythematosus may be more likely than others to experience a prolonged remission, new data suggest.

In a study of more than 1,500 patients who had SLE, about 2% achieved a remission lasting at least 5 years on either no medication or only antimalarial drugs, Anjali Papneja reported at the annual meeting of the Canadian Rheumatology Association.

The prolonged remissions lasted on average almost 12 years. Nearly a third of the patients had had a monophasic clinical disease course, characterized by only a single flare, before their remission.

Patients achieving a prolonged remission were more likely to be white, had milder disease, and were less likely to have involvement of certain organ systems and to have received steroids or other immunosuppressive agents prior to remission onset.

"Prolonged remission is an infrequent outcome among SLE patients, but it generally lasts for over a decade, and it is preceded by an atypically monophasic clinical course in a significant minority," Ms. Papneja commented.

"We want to know what makes these patients different, how they can be treated most effectively, and how we can harness this unique and desirable outcome more generally," she added.

An attendee asked what the remission rate was if patients who achieved remission on stable immunosuppressive regimens and/or low-dose prednisone were also included.

The reason for including only those patients who had remitted off all steroids and immunosuppressive agents was to distinguish those whose SLE was in true remission (i.e., those in the cohort), from those whose disease was merely suppressed by the ongoing use of these medications, replied Ms. Papneja, a medical student at the University of Toronto. "But they do remain on antimalarials because in recent decades, it has been found that these patients have cardiovascular protective benefits from antimalarials."

The investigators studied all patients with SLE followed at the university’s Lupus Clinic from July 1970 through May 2011.

Patients were defined as having a prolonged remission if they did not have any clinical disease activity for at least 5 years, had regular clinic visits, and received no immunosuppressive medications or at most antimalarial drugs during the remission.

With a mean duration of follow-up of nearly 22 years, 2.4% of the 1,613 patients studied achieved a prolonged remission, after a mean disease duration of about 9 years. These sustained remissions lasted an average of nearly 12 years.

By type, 44% of the remissions were serologically and clinically quiescent, 28% were serologically active but clinically quiescent, and 28% fluctuated between these types.

In the years leading up to the remission, the majority of patients (71%) had a relapsing-remitting clinical course, but a sizable proportion (29%) had a monophasic course. "It’s worthwhile to study these patients further to determine at what point we can safely define a disease course as being monophasic," Ms. Papneja commented. None of the patients achieving prolonged remission had a chronic active course.

In a case-control comparison, in which each patient who achieved prolonged remission was matched with three who did not, the former were more likely to be white (82% vs. 72%), had a lower SLE Disease Activity Index (SLEDAI-2K) score at their first clinic visit (8 vs. 10.6), and had a lower adjusted mean SLEDAI-2K score in the 3 years leading up to remission (3 vs. 5.9).

The group achieving prolonged remission was also significantly less likely to have skin, pulmonary, and central nervous system involvement, but "we noted that there was no difference in renal involvement between cases and controls," she pointed out. Additionally, they were less likely to have received steroids (58% vs. 80%) and other immunosuppressive agents (24% vs. 47%) prior to remission onset, also seeming to point to milder disease.

A study limitation, Ms. Papneja acknowledged, was that only patients continuing care at the clinic were included, and the clinic’s attrition rate was about 10%. Thus, some patients achieving remission and dropping out of care, or having a flare and seeking treatment elsewhere, may have been lost to follow-up.

Ms. Papneja disclosed that she had no relevant conflicts of interest.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.