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Fusidic Acid Resistance Persists Despite Moves to Curb Its Use
MANCHESTER, ENGLAND — Levels of fusidic acid-resistant Staphylococcus aureus have not fallen despite efforts to limit the use of this topical antibiotic, which suggests that a community reservoir of resistance has developed, Dr. Angana Mitra said at the annual meeting of the British Association of Dermatologists.
High levels of fusidic acid-resistant S. aureus (FRSA) have been reported in the United Kingdom previously, particularly in dermatology patients. In an audit done over a 4-month period in 2001, resistant isolates were identified in 50% of dermatology patients, in 9% of primary care patients, 10% of hospital inpatients, and 10% of nondermatology outpatients, said Dr. Mitra of the department of dermatology, Dewsbury District Hospital, West Yorkshire, England. An active education program was undertaken on the appropriate use of topical antibiotics, and a repeat audit was done over the same 4-month period in 2004.
The total number of S. aureus isolates was much higher in 2004, at 604, than in 2001, at 349. This is likely to reflect an increased awareness of antibiotic resistance in general, with more swabs being taken, she said.
In 2001, the level of FRSA in primary care, hospital inpatients, and nondermatology outpatients was similar, at 10%. In comparison, at that time, 50% of dermatology patients had FRSA. The level in dermatology fell slightly and not significantly by 2004, to 41%. However, the level had doubled among hospital inpatients and almost tripled in primary care and nondermatology outpatients.
Topical fusidic acid use within the previous 6 months was reported by 63% of dermatology patients in 2001 (Br. J. Dermatol. 2003;148:1018–20). This fell to 15% in 2004.
Hospital prescriptions for topical fusidic acid also fell, from an average of 42 per month to 1–2 per month, and the number of community prescriptions also decreased significantly, but there was no corresponding drop in FRSA, Dr. Mitra said. Persistence of FRSA suggests the presence of a reservoir in the community, and there may be a lag period before this clears. “We therefore advocate continued control on topical fusidic acid use,” she said.
The drug should be used for short periods and for appropriate indications. In 2001 and 2004, the most common reason for using fusidic acid was not staphylococcal skin infection but atopic eczema, said Dr. Mitra, adding that, for the first time, FRSA also resistant to methicillin was identified in 11% of patients.
MANCHESTER, ENGLAND — Levels of fusidic acid-resistant Staphylococcus aureus have not fallen despite efforts to limit the use of this topical antibiotic, which suggests that a community reservoir of resistance has developed, Dr. Angana Mitra said at the annual meeting of the British Association of Dermatologists.
High levels of fusidic acid-resistant S. aureus (FRSA) have been reported in the United Kingdom previously, particularly in dermatology patients. In an audit done over a 4-month period in 2001, resistant isolates were identified in 50% of dermatology patients, in 9% of primary care patients, 10% of hospital inpatients, and 10% of nondermatology outpatients, said Dr. Mitra of the department of dermatology, Dewsbury District Hospital, West Yorkshire, England. An active education program was undertaken on the appropriate use of topical antibiotics, and a repeat audit was done over the same 4-month period in 2004.
The total number of S. aureus isolates was much higher in 2004, at 604, than in 2001, at 349. This is likely to reflect an increased awareness of antibiotic resistance in general, with more swabs being taken, she said.
In 2001, the level of FRSA in primary care, hospital inpatients, and nondermatology outpatients was similar, at 10%. In comparison, at that time, 50% of dermatology patients had FRSA. The level in dermatology fell slightly and not significantly by 2004, to 41%. However, the level had doubled among hospital inpatients and almost tripled in primary care and nondermatology outpatients.
Topical fusidic acid use within the previous 6 months was reported by 63% of dermatology patients in 2001 (Br. J. Dermatol. 2003;148:1018–20). This fell to 15% in 2004.
Hospital prescriptions for topical fusidic acid also fell, from an average of 42 per month to 1–2 per month, and the number of community prescriptions also decreased significantly, but there was no corresponding drop in FRSA, Dr. Mitra said. Persistence of FRSA suggests the presence of a reservoir in the community, and there may be a lag period before this clears. “We therefore advocate continued control on topical fusidic acid use,” she said.
The drug should be used for short periods and for appropriate indications. In 2001 and 2004, the most common reason for using fusidic acid was not staphylococcal skin infection but atopic eczema, said Dr. Mitra, adding that, for the first time, FRSA also resistant to methicillin was identified in 11% of patients.
MANCHESTER, ENGLAND — Levels of fusidic acid-resistant Staphylococcus aureus have not fallen despite efforts to limit the use of this topical antibiotic, which suggests that a community reservoir of resistance has developed, Dr. Angana Mitra said at the annual meeting of the British Association of Dermatologists.
High levels of fusidic acid-resistant S. aureus (FRSA) have been reported in the United Kingdom previously, particularly in dermatology patients. In an audit done over a 4-month period in 2001, resistant isolates were identified in 50% of dermatology patients, in 9% of primary care patients, 10% of hospital inpatients, and 10% of nondermatology outpatients, said Dr. Mitra of the department of dermatology, Dewsbury District Hospital, West Yorkshire, England. An active education program was undertaken on the appropriate use of topical antibiotics, and a repeat audit was done over the same 4-month period in 2004.
The total number of S. aureus isolates was much higher in 2004, at 604, than in 2001, at 349. This is likely to reflect an increased awareness of antibiotic resistance in general, with more swabs being taken, she said.
In 2001, the level of FRSA in primary care, hospital inpatients, and nondermatology outpatients was similar, at 10%. In comparison, at that time, 50% of dermatology patients had FRSA. The level in dermatology fell slightly and not significantly by 2004, to 41%. However, the level had doubled among hospital inpatients and almost tripled in primary care and nondermatology outpatients.
Topical fusidic acid use within the previous 6 months was reported by 63% of dermatology patients in 2001 (Br. J. Dermatol. 2003;148:1018–20). This fell to 15% in 2004.
Hospital prescriptions for topical fusidic acid also fell, from an average of 42 per month to 1–2 per month, and the number of community prescriptions also decreased significantly, but there was no corresponding drop in FRSA, Dr. Mitra said. Persistence of FRSA suggests the presence of a reservoir in the community, and there may be a lag period before this clears. “We therefore advocate continued control on topical fusidic acid use,” she said.
The drug should be used for short periods and for appropriate indications. In 2001 and 2004, the most common reason for using fusidic acid was not staphylococcal skin infection but atopic eczema, said Dr. Mitra, adding that, for the first time, FRSA also resistant to methicillin was identified in 11% of patients.
Lupus Features Vary Dramatically by ANA Status
AMSTERDAM — New pieces of the clinical, serologic, and therapeutic puzzle of systemic lupus erythematosus have emerged in a post hoc analysis of a study evaluating belimumab, an investigational agent that targets B cells.
Review of data from a large, phase II study found that patients who are antinuclear antibody (ANA) positive exhibit different clinical and serologic features than do patients who are ANA negative, according to Dr. Michelle Petri, who presented her observations in a poster session at the annual European Congress of Rheumatology.
Those who were ANA positive were more likely to have a history of renal or hematologic involvement, exhibited higher disease activity, and required more prednisone, she reported. For example, the analysis determined that at baseline, 34% and 59% of seropositive patients had renal and hematologic involvement, respectively, compared with 19% and 33% of seronegative patients.
Seropositive patients also had significantly higher levels of IgG, IgA, and IgE, and B-lymphocyte stimulator (BLyS), which is a potent costimulator of B cells. Elevated levels of BLyS, seen in 51% of the seropositive patients and in 24% of the seronegative patients, are thought to play a role in B-cell-mediated autoimmunity, according to Dr. Petri, professor of rheumatology, Johns Hopkins University, Baltimore.
ANA-positive patients also had lower levels of CD20-positive B cells, as well as lower levels of naive, activated, and memory B cells. This suggests that SLE disease activity may relate to B-cell dysfunction and that B-cell-directed therapy “would be appropriate” in serologically active, ANA positive patients, Dr. Petri commented. This connection needs to be proved in a subsequent trial, “but it makes sense in terms of what we know about lupus,” she added.
These observations were derived from a trial that compared intravenous belimumab (LymphoStat, Human Genome Sciences, Rockville, Md.), 1, 4, or 10 mg/kg with placebo plus standard of care treatment in 449 patients. The drug was given on days 0, 14, 28, and then monthly for 52 weeks at 59 sites in North America.
Investigator-determined standard of care treatment included the use of nonsteroidal anti-inflammatory drugs, antimalarials, corticosteroids, and immunosuppressants.
The primary end points of the trial were percent change in SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment Trial-Systemic Lupus Erythematosus Disease Activity Index) at week 24 and time to first flare over 52 weeks.
These end points were not met, according to Dr. Dan Wallace, who presented the data at the meeting, which was sponsored by the European League Against Rheumatism. The reason for the failure to reach statistical significance was the inclusion of ANA-negative patients in the trial, Dr. Wallace said in an interview. “A lot of those patients probably did not have lupus.” For inclusion in the study, patients had to have been ANA positive at some time in the course of their disease, but at the time of screening only 72% were serologically active, with an ANA titer of 1:80 or higher and/or an antidouble-stranded DNA level of 30 IU or greater, said Dr. Wallace of the David Geffen School of Medicine, University of California, Los Angeles.
“If you analyze only those who are ANA or anti-DNA positive the end points were met and the drug was quite effective.” Serologic findings seen in the study included significant reductions in various types of B cells, including a median 54% reduction in CD20-positive cells, a 62% reduction in plasmacytoid cells, and a 70% reduction in activated B cells, Dr. Wallace reported.
Serologically active patients also showed stabilization of disease on individual organ domains as measured by the British Isles Lupus Assessment Group (BILAG) scores, according to Dr. Richard Furie of North Shore-Long Island Jewish Health System, Manhasset, N.Y.
This connection needs to be proved in a subsequent trial, 'but it makes sense in terms of what we know.' DR. PETRI
AMSTERDAM — New pieces of the clinical, serologic, and therapeutic puzzle of systemic lupus erythematosus have emerged in a post hoc analysis of a study evaluating belimumab, an investigational agent that targets B cells.
Review of data from a large, phase II study found that patients who are antinuclear antibody (ANA) positive exhibit different clinical and serologic features than do patients who are ANA negative, according to Dr. Michelle Petri, who presented her observations in a poster session at the annual European Congress of Rheumatology.
Those who were ANA positive were more likely to have a history of renal or hematologic involvement, exhibited higher disease activity, and required more prednisone, she reported. For example, the analysis determined that at baseline, 34% and 59% of seropositive patients had renal and hematologic involvement, respectively, compared with 19% and 33% of seronegative patients.
Seropositive patients also had significantly higher levels of IgG, IgA, and IgE, and B-lymphocyte stimulator (BLyS), which is a potent costimulator of B cells. Elevated levels of BLyS, seen in 51% of the seropositive patients and in 24% of the seronegative patients, are thought to play a role in B-cell-mediated autoimmunity, according to Dr. Petri, professor of rheumatology, Johns Hopkins University, Baltimore.
ANA-positive patients also had lower levels of CD20-positive B cells, as well as lower levels of naive, activated, and memory B cells. This suggests that SLE disease activity may relate to B-cell dysfunction and that B-cell-directed therapy “would be appropriate” in serologically active, ANA positive patients, Dr. Petri commented. This connection needs to be proved in a subsequent trial, “but it makes sense in terms of what we know about lupus,” she added.
These observations were derived from a trial that compared intravenous belimumab (LymphoStat, Human Genome Sciences, Rockville, Md.), 1, 4, or 10 mg/kg with placebo plus standard of care treatment in 449 patients. The drug was given on days 0, 14, 28, and then monthly for 52 weeks at 59 sites in North America.
Investigator-determined standard of care treatment included the use of nonsteroidal anti-inflammatory drugs, antimalarials, corticosteroids, and immunosuppressants.
The primary end points of the trial were percent change in SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment Trial-Systemic Lupus Erythematosus Disease Activity Index) at week 24 and time to first flare over 52 weeks.
These end points were not met, according to Dr. Dan Wallace, who presented the data at the meeting, which was sponsored by the European League Against Rheumatism. The reason for the failure to reach statistical significance was the inclusion of ANA-negative patients in the trial, Dr. Wallace said in an interview. “A lot of those patients probably did not have lupus.” For inclusion in the study, patients had to have been ANA positive at some time in the course of their disease, but at the time of screening only 72% were serologically active, with an ANA titer of 1:80 or higher and/or an antidouble-stranded DNA level of 30 IU or greater, said Dr. Wallace of the David Geffen School of Medicine, University of California, Los Angeles.
“If you analyze only those who are ANA or anti-DNA positive the end points were met and the drug was quite effective.” Serologic findings seen in the study included significant reductions in various types of B cells, including a median 54% reduction in CD20-positive cells, a 62% reduction in plasmacytoid cells, and a 70% reduction in activated B cells, Dr. Wallace reported.
Serologically active patients also showed stabilization of disease on individual organ domains as measured by the British Isles Lupus Assessment Group (BILAG) scores, according to Dr. Richard Furie of North Shore-Long Island Jewish Health System, Manhasset, N.Y.
This connection needs to be proved in a subsequent trial, 'but it makes sense in terms of what we know.' DR. PETRI
AMSTERDAM — New pieces of the clinical, serologic, and therapeutic puzzle of systemic lupus erythematosus have emerged in a post hoc analysis of a study evaluating belimumab, an investigational agent that targets B cells.
Review of data from a large, phase II study found that patients who are antinuclear antibody (ANA) positive exhibit different clinical and serologic features than do patients who are ANA negative, according to Dr. Michelle Petri, who presented her observations in a poster session at the annual European Congress of Rheumatology.
Those who were ANA positive were more likely to have a history of renal or hematologic involvement, exhibited higher disease activity, and required more prednisone, she reported. For example, the analysis determined that at baseline, 34% and 59% of seropositive patients had renal and hematologic involvement, respectively, compared with 19% and 33% of seronegative patients.
Seropositive patients also had significantly higher levels of IgG, IgA, and IgE, and B-lymphocyte stimulator (BLyS), which is a potent costimulator of B cells. Elevated levels of BLyS, seen in 51% of the seropositive patients and in 24% of the seronegative patients, are thought to play a role in B-cell-mediated autoimmunity, according to Dr. Petri, professor of rheumatology, Johns Hopkins University, Baltimore.
ANA-positive patients also had lower levels of CD20-positive B cells, as well as lower levels of naive, activated, and memory B cells. This suggests that SLE disease activity may relate to B-cell dysfunction and that B-cell-directed therapy “would be appropriate” in serologically active, ANA positive patients, Dr. Petri commented. This connection needs to be proved in a subsequent trial, “but it makes sense in terms of what we know about lupus,” she added.
These observations were derived from a trial that compared intravenous belimumab (LymphoStat, Human Genome Sciences, Rockville, Md.), 1, 4, or 10 mg/kg with placebo plus standard of care treatment in 449 patients. The drug was given on days 0, 14, 28, and then monthly for 52 weeks at 59 sites in North America.
Investigator-determined standard of care treatment included the use of nonsteroidal anti-inflammatory drugs, antimalarials, corticosteroids, and immunosuppressants.
The primary end points of the trial were percent change in SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment Trial-Systemic Lupus Erythematosus Disease Activity Index) at week 24 and time to first flare over 52 weeks.
These end points were not met, according to Dr. Dan Wallace, who presented the data at the meeting, which was sponsored by the European League Against Rheumatism. The reason for the failure to reach statistical significance was the inclusion of ANA-negative patients in the trial, Dr. Wallace said in an interview. “A lot of those patients probably did not have lupus.” For inclusion in the study, patients had to have been ANA positive at some time in the course of their disease, but at the time of screening only 72% were serologically active, with an ANA titer of 1:80 or higher and/or an antidouble-stranded DNA level of 30 IU or greater, said Dr. Wallace of the David Geffen School of Medicine, University of California, Los Angeles.
“If you analyze only those who are ANA or anti-DNA positive the end points were met and the drug was quite effective.” Serologic findings seen in the study included significant reductions in various types of B cells, including a median 54% reduction in CD20-positive cells, a 62% reduction in plasmacytoid cells, and a 70% reduction in activated B cells, Dr. Wallace reported.
Serologically active patients also showed stabilization of disease on individual organ domains as measured by the British Isles Lupus Assessment Group (BILAG) scores, according to Dr. Richard Furie of North Shore-Long Island Jewish Health System, Manhasset, N.Y.
This connection needs to be proved in a subsequent trial, 'but it makes sense in terms of what we know.' DR. PETRI
Early RA Remits in Half After a Year of DMARDs
AMSTERDAM — Initial therapy using traditional disease-modifying anti-rheumatic drugs—even early, aggressively, and in combination—is inadequate for a significant proportion of patients with inflammatory arthritis, according to preliminary data from a prospective Canadian study.
In rheumatoid arthritis (RA), joint damage and the resulting disability occur during the first years of disease, and current therapeutic strategies aim to be aggressive in minimizing inflammation and preventing irreversible damage.
But among a cohort of 79 patients followed for 12 months in a real-world setting, fewer than half achieved remission with disease-modifying antirheumatic drug (DMARD) treatment, Dr. Vivian P. Bykerk said at the annual European Congress of Rheumatology.
For inclusion in the Toronto Early Arthritis Cohort, patients were required to be at least 16 years old and to have had symptoms for at least 6 weeks but less than 1 year. They had to have at least two swollen joints or one swollen metacarpophalangeal joint or proximal interphalangeal joint and to have more than one of the following characteristics: rheumatoid factor positive, anti-CCP positive, morning stiffness exceeding 45 minutes' duration, a response to nonsteroidal anti-inflammatory drugs, and a painful metatarsophalangeal joint squeeze test.
At baseline the mean patient age was 45.5 years, and 80% were female. Median duration of symptoms was 161 days at the time of evaluation.
Mean erythrocyte sedimentation rate was 28 mm/h, and mean C-reactive protein level was 13 mg/L. The mean tender joint count was 19, mean swollen joint count was 11, and mean Disease Activity Score (DAS) was 5.3. A total of 28% of patients were rheumatoid factor positive, and 67% met the criteria for RA. In addition, 26% already had erosions present in the hands or feet.
Recommended initial treatment for RA in Canada involves combination therapy, but only 60% of patients in this cohort were started on more than one DMARD. This probably reflects a lower disease burden and also possibly patient preference, said Dr. Bykerk of Mount Sinai Hospital, Toronto.
When combination therapy was used, it generally was methotrexate plus hydroxychloroquine or sulfasalazine. The methotrexate dose was 15–25 mg/week, the mean dose at 12 months was 18 mg/week, and for two-thirds of patients the dose exceeded 20 mg/week. A third of the patients opted to take their methotrexate subcutaneously, she said. “In Canada we are strong proponents of subcutaneous methotrexate in doses of 20–25 mg early on,” she said.
The sulfasalazine dose was 2 g/day, and the hydroxychloroquine dose was 400 mg/day.
“Very few patients received biologics at the outset, because it's very difficult to access these drugs in our province and country using public health drug coverage,” she said at the meeting, sponsored by the European League Against Rheumatism. Only after 6–9 months can patients in Canada begin to access biologics, she said.
By 12 months, only 47% of patients achieved remission as defined as a DAS28 less than 2.6, even when receiving an aggressive DMARD strategy followed by biologic therapies in patients whose disease responded inadequately at 6 months.
“Although the data are still preliminary, for a significant proportion of patients with early RA or inflammatory arthritis, a different strategy than early DMARD therapy may be required,” she said.
Studies are needed to validate that the earlier use of biologics is more effective in protecting the joint against the destruction of RA and inflammatory arthritis and to identify prognostic factors or biomarkers that can predict who will not respond to an initial DMARD strategy including high-dose methotrexate, according to Dr. Bykerk.
AMSTERDAM — Initial therapy using traditional disease-modifying anti-rheumatic drugs—even early, aggressively, and in combination—is inadequate for a significant proportion of patients with inflammatory arthritis, according to preliminary data from a prospective Canadian study.
In rheumatoid arthritis (RA), joint damage and the resulting disability occur during the first years of disease, and current therapeutic strategies aim to be aggressive in minimizing inflammation and preventing irreversible damage.
But among a cohort of 79 patients followed for 12 months in a real-world setting, fewer than half achieved remission with disease-modifying antirheumatic drug (DMARD) treatment, Dr. Vivian P. Bykerk said at the annual European Congress of Rheumatology.
For inclusion in the Toronto Early Arthritis Cohort, patients were required to be at least 16 years old and to have had symptoms for at least 6 weeks but less than 1 year. They had to have at least two swollen joints or one swollen metacarpophalangeal joint or proximal interphalangeal joint and to have more than one of the following characteristics: rheumatoid factor positive, anti-CCP positive, morning stiffness exceeding 45 minutes' duration, a response to nonsteroidal anti-inflammatory drugs, and a painful metatarsophalangeal joint squeeze test.
At baseline the mean patient age was 45.5 years, and 80% were female. Median duration of symptoms was 161 days at the time of evaluation.
Mean erythrocyte sedimentation rate was 28 mm/h, and mean C-reactive protein level was 13 mg/L. The mean tender joint count was 19, mean swollen joint count was 11, and mean Disease Activity Score (DAS) was 5.3. A total of 28% of patients were rheumatoid factor positive, and 67% met the criteria for RA. In addition, 26% already had erosions present in the hands or feet.
Recommended initial treatment for RA in Canada involves combination therapy, but only 60% of patients in this cohort were started on more than one DMARD. This probably reflects a lower disease burden and also possibly patient preference, said Dr. Bykerk of Mount Sinai Hospital, Toronto.
When combination therapy was used, it generally was methotrexate plus hydroxychloroquine or sulfasalazine. The methotrexate dose was 15–25 mg/week, the mean dose at 12 months was 18 mg/week, and for two-thirds of patients the dose exceeded 20 mg/week. A third of the patients opted to take their methotrexate subcutaneously, she said. “In Canada we are strong proponents of subcutaneous methotrexate in doses of 20–25 mg early on,” she said.
The sulfasalazine dose was 2 g/day, and the hydroxychloroquine dose was 400 mg/day.
“Very few patients received biologics at the outset, because it's very difficult to access these drugs in our province and country using public health drug coverage,” she said at the meeting, sponsored by the European League Against Rheumatism. Only after 6–9 months can patients in Canada begin to access biologics, she said.
By 12 months, only 47% of patients achieved remission as defined as a DAS28 less than 2.6, even when receiving an aggressive DMARD strategy followed by biologic therapies in patients whose disease responded inadequately at 6 months.
“Although the data are still preliminary, for a significant proportion of patients with early RA or inflammatory arthritis, a different strategy than early DMARD therapy may be required,” she said.
Studies are needed to validate that the earlier use of biologics is more effective in protecting the joint against the destruction of RA and inflammatory arthritis and to identify prognostic factors or biomarkers that can predict who will not respond to an initial DMARD strategy including high-dose methotrexate, according to Dr. Bykerk.
AMSTERDAM — Initial therapy using traditional disease-modifying anti-rheumatic drugs—even early, aggressively, and in combination—is inadequate for a significant proportion of patients with inflammatory arthritis, according to preliminary data from a prospective Canadian study.
In rheumatoid arthritis (RA), joint damage and the resulting disability occur during the first years of disease, and current therapeutic strategies aim to be aggressive in minimizing inflammation and preventing irreversible damage.
But among a cohort of 79 patients followed for 12 months in a real-world setting, fewer than half achieved remission with disease-modifying antirheumatic drug (DMARD) treatment, Dr. Vivian P. Bykerk said at the annual European Congress of Rheumatology.
For inclusion in the Toronto Early Arthritis Cohort, patients were required to be at least 16 years old and to have had symptoms for at least 6 weeks but less than 1 year. They had to have at least two swollen joints or one swollen metacarpophalangeal joint or proximal interphalangeal joint and to have more than one of the following characteristics: rheumatoid factor positive, anti-CCP positive, morning stiffness exceeding 45 minutes' duration, a response to nonsteroidal anti-inflammatory drugs, and a painful metatarsophalangeal joint squeeze test.
At baseline the mean patient age was 45.5 years, and 80% were female. Median duration of symptoms was 161 days at the time of evaluation.
Mean erythrocyte sedimentation rate was 28 mm/h, and mean C-reactive protein level was 13 mg/L. The mean tender joint count was 19, mean swollen joint count was 11, and mean Disease Activity Score (DAS) was 5.3. A total of 28% of patients were rheumatoid factor positive, and 67% met the criteria for RA. In addition, 26% already had erosions present in the hands or feet.
Recommended initial treatment for RA in Canada involves combination therapy, but only 60% of patients in this cohort were started on more than one DMARD. This probably reflects a lower disease burden and also possibly patient preference, said Dr. Bykerk of Mount Sinai Hospital, Toronto.
When combination therapy was used, it generally was methotrexate plus hydroxychloroquine or sulfasalazine. The methotrexate dose was 15–25 mg/week, the mean dose at 12 months was 18 mg/week, and for two-thirds of patients the dose exceeded 20 mg/week. A third of the patients opted to take their methotrexate subcutaneously, she said. “In Canada we are strong proponents of subcutaneous methotrexate in doses of 20–25 mg early on,” she said.
The sulfasalazine dose was 2 g/day, and the hydroxychloroquine dose was 400 mg/day.
“Very few patients received biologics at the outset, because it's very difficult to access these drugs in our province and country using public health drug coverage,” she said at the meeting, sponsored by the European League Against Rheumatism. Only after 6–9 months can patients in Canada begin to access biologics, she said.
By 12 months, only 47% of patients achieved remission as defined as a DAS28 less than 2.6, even when receiving an aggressive DMARD strategy followed by biologic therapies in patients whose disease responded inadequately at 6 months.
“Although the data are still preliminary, for a significant proportion of patients with early RA or inflammatory arthritis, a different strategy than early DMARD therapy may be required,” she said.
Studies are needed to validate that the earlier use of biologics is more effective in protecting the joint against the destruction of RA and inflammatory arthritis and to identify prognostic factors or biomarkers that can predict who will not respond to an initial DMARD strategy including high-dose methotrexate, according to Dr. Bykerk.
Phase II Efficacy Seen With New TNF Blocking Agent
AMSTERDAM — The therapeutic options for patients with rheumatoid arthritis who do not respond to methotrexate alone continue to expand, with a new tumor necrosis factor-α blocker showing efficacy in a phase II trial.
In preclinical studies, the human monoclonal antibody golimumab was shown to be more effective at neutralizing tumor necrosis factor-α (TNF-α) than the other currently available biologic agents, Dr. Jonathan Kay wrote in a poster session at the annual European Congress of Rheumatology.
And while golimumab must be given subcutaneously, the dosing interval is once every 4 weeks rather than twice weekly as is the case with etanercept, or every other week as with adalimumab. Because the drug can be given once a month, it may provide a convenient alternative for patients, Dr. Kay told RHEUMATOLOGY NEWS in an interview.
The investigators randomly assigned 172 patients with rheumatoid arthritis (RA) of at least 3 months' duration to placebo or treatment with golimumab with one of four dosages: 50 mg every 2 weeks, 50 mg every 4 weeks, 100 mg every 2 weeks, or 100 mg every 4 weeks. All patients also were on stable doses of methotrexate.
At week 16, 62% of patients who were receiving golimumab plus methotrexate achieved an American College of Rheumatology 20 response, which was the primary end point, compared with 37% of those patients who were receiving placebo plus stable doses of methotrexate, according to Dr. Kay of the rheumatology unit at Massachusetts General Hospital, Boston.
A secondary end point of the trial was the Disease Activity Score 28 response to active and placebo treatments.
This outcome measure can be calculated using either the erythrocyte sedimentation rate or C-reactive protein levels, and patients' responses to therapies are categorized as good, moderate, remission, and nonresponse.
Using the erythrocyte sedimentation rate, Disease Activity Score 28 remission plus good/moderate responses were seen in 72% and 10% of the golimumab and placebo groups, respectively, and in 74% and 27%, respectively, using C-reactive protein levels.
Serious adverse events were reported by 8% of patients receiving golimumab plus methotrexate and by 5.9% of those receiving methotrexate plus placebo.
“Clinically relevant” adverse events reported in the golimumab group included two cases of pneumonia, one case of heart failure, one case of lung cancer, and one case of cardiac tamponade, Dr. Kay reported.
There were no deaths or cases of tuberculosis or opportunistic infections, however.
The phase II study was supported by Centocor Research and Development Inc. The pharmaceutical company has initiated Phase III studies that are underway to evaluate golimumab in patients with RA, psoriatic arthritis, and ankylosing spondylitis.
The drug is being given in doses of 50 or 100 mg every 4 weeks in these trials, which will follow patients for 5 years.
AMSTERDAM — The therapeutic options for patients with rheumatoid arthritis who do not respond to methotrexate alone continue to expand, with a new tumor necrosis factor-α blocker showing efficacy in a phase II trial.
In preclinical studies, the human monoclonal antibody golimumab was shown to be more effective at neutralizing tumor necrosis factor-α (TNF-α) than the other currently available biologic agents, Dr. Jonathan Kay wrote in a poster session at the annual European Congress of Rheumatology.
And while golimumab must be given subcutaneously, the dosing interval is once every 4 weeks rather than twice weekly as is the case with etanercept, or every other week as with adalimumab. Because the drug can be given once a month, it may provide a convenient alternative for patients, Dr. Kay told RHEUMATOLOGY NEWS in an interview.
The investigators randomly assigned 172 patients with rheumatoid arthritis (RA) of at least 3 months' duration to placebo or treatment with golimumab with one of four dosages: 50 mg every 2 weeks, 50 mg every 4 weeks, 100 mg every 2 weeks, or 100 mg every 4 weeks. All patients also were on stable doses of methotrexate.
At week 16, 62% of patients who were receiving golimumab plus methotrexate achieved an American College of Rheumatology 20 response, which was the primary end point, compared with 37% of those patients who were receiving placebo plus stable doses of methotrexate, according to Dr. Kay of the rheumatology unit at Massachusetts General Hospital, Boston.
A secondary end point of the trial was the Disease Activity Score 28 response to active and placebo treatments.
This outcome measure can be calculated using either the erythrocyte sedimentation rate or C-reactive protein levels, and patients' responses to therapies are categorized as good, moderate, remission, and nonresponse.
Using the erythrocyte sedimentation rate, Disease Activity Score 28 remission plus good/moderate responses were seen in 72% and 10% of the golimumab and placebo groups, respectively, and in 74% and 27%, respectively, using C-reactive protein levels.
Serious adverse events were reported by 8% of patients receiving golimumab plus methotrexate and by 5.9% of those receiving methotrexate plus placebo.
“Clinically relevant” adverse events reported in the golimumab group included two cases of pneumonia, one case of heart failure, one case of lung cancer, and one case of cardiac tamponade, Dr. Kay reported.
There were no deaths or cases of tuberculosis or opportunistic infections, however.
The phase II study was supported by Centocor Research and Development Inc. The pharmaceutical company has initiated Phase III studies that are underway to evaluate golimumab in patients with RA, psoriatic arthritis, and ankylosing spondylitis.
The drug is being given in doses of 50 or 100 mg every 4 weeks in these trials, which will follow patients for 5 years.
AMSTERDAM — The therapeutic options for patients with rheumatoid arthritis who do not respond to methotrexate alone continue to expand, with a new tumor necrosis factor-α blocker showing efficacy in a phase II trial.
In preclinical studies, the human monoclonal antibody golimumab was shown to be more effective at neutralizing tumor necrosis factor-α (TNF-α) than the other currently available biologic agents, Dr. Jonathan Kay wrote in a poster session at the annual European Congress of Rheumatology.
And while golimumab must be given subcutaneously, the dosing interval is once every 4 weeks rather than twice weekly as is the case with etanercept, or every other week as with adalimumab. Because the drug can be given once a month, it may provide a convenient alternative for patients, Dr. Kay told RHEUMATOLOGY NEWS in an interview.
The investigators randomly assigned 172 patients with rheumatoid arthritis (RA) of at least 3 months' duration to placebo or treatment with golimumab with one of four dosages: 50 mg every 2 weeks, 50 mg every 4 weeks, 100 mg every 2 weeks, or 100 mg every 4 weeks. All patients also were on stable doses of methotrexate.
At week 16, 62% of patients who were receiving golimumab plus methotrexate achieved an American College of Rheumatology 20 response, which was the primary end point, compared with 37% of those patients who were receiving placebo plus stable doses of methotrexate, according to Dr. Kay of the rheumatology unit at Massachusetts General Hospital, Boston.
A secondary end point of the trial was the Disease Activity Score 28 response to active and placebo treatments.
This outcome measure can be calculated using either the erythrocyte sedimentation rate or C-reactive protein levels, and patients' responses to therapies are categorized as good, moderate, remission, and nonresponse.
Using the erythrocyte sedimentation rate, Disease Activity Score 28 remission plus good/moderate responses were seen in 72% and 10% of the golimumab and placebo groups, respectively, and in 74% and 27%, respectively, using C-reactive protein levels.
Serious adverse events were reported by 8% of patients receiving golimumab plus methotrexate and by 5.9% of those receiving methotrexate plus placebo.
“Clinically relevant” adverse events reported in the golimumab group included two cases of pneumonia, one case of heart failure, one case of lung cancer, and one case of cardiac tamponade, Dr. Kay reported.
There were no deaths or cases of tuberculosis or opportunistic infections, however.
The phase II study was supported by Centocor Research and Development Inc. The pharmaceutical company has initiated Phase III studies that are underway to evaluate golimumab in patients with RA, psoriatic arthritis, and ankylosing spondylitis.
The drug is being given in doses of 50 or 100 mg every 4 weeks in these trials, which will follow patients for 5 years.
Biomarker Predicts Joint Damage At 10 Years in Patients With RA
AMSTERDAM — Baseline levels of the leukocyte protein calprotectin in patients with rheumatoid arthritis correlated with clinical and radiographic outcomes at 10 years in a prospective longitudinal study, suggesting that this biomarker may be a useful predictor of joint damage, Dr. Hilde Berner Hammer reported at the annual European Congress of Rheumatology.
A cohort of 145 patients with early rheumatoid arthritis (RA) were enrolled during 1991 and 1992—before the era of biologic treatment—from the rheumatology departments of Diakonhjemmet Hospital in Oslo and University Hospital Maastricht (the Netherlands).
Baseline measurements included calprotectin levels, erythrocyte sedimentation rates (ESRs), and C-reactive protein levels. Radiographs of the hands were obtained, and modified Sharp scores were calculated. Damage was assessed according to the RA articular damage (RAAD) score and all measurements were repeated at 10 years, Dr. Berner Hammer wrote in a poster session at the meeting, sponsored by the European League Against Rheumatism.
The 88 patients with elevated levels of calprotectin (0.9 mg/L or more) at baseline and at 10 years also had high modified Sharp and RAAD scores at both time points. (See box.)
Moreover, patients who were rheumatoid factor positive had elevated calprotectin levels as well as high ESRs, modified Sharp scores, and RAAD scores, according to Dr. Berner Hammer of Diakonhjemmet Hospital.
Calprotectin is one of the calcium-binding proinflammatory S100 proteins released during cell activation. High levels of the protein have been found in the synovial fluid of RA patients. It is also upregulated in other immunopathologic conditions, particularly in the setting of acute inflammation or Th1-mediated reactions (Physiol. Res. 2004;53:245–53). An immunoassay for the detection of fecal calprotectin in patients with inflammatory bowel disease—marketed as PhiCal by Genova Diagnostics Inc.—was recently approved by the Food and Drug Administration.
This marker has also been investigated as a measure of disease activity in polymyalgia rheumatica and temporal arteritis. A group of 47 patients, 33 with polymyalgia rheumatica, 10 with temporal arteritis, and 4 with both conditions, were followed prospectively for up to 3 years. Calprotectin was highly correlated with acute phase parameters and ESRs, and levels fell significantly after the initiation of prednisone therapy (Scand. J. Rheumatol. 2005;34:125–8).
ELSEVIER GLOBAL MEDICAL NEWS
AMSTERDAM — Baseline levels of the leukocyte protein calprotectin in patients with rheumatoid arthritis correlated with clinical and radiographic outcomes at 10 years in a prospective longitudinal study, suggesting that this biomarker may be a useful predictor of joint damage, Dr. Hilde Berner Hammer reported at the annual European Congress of Rheumatology.
A cohort of 145 patients with early rheumatoid arthritis (RA) were enrolled during 1991 and 1992—before the era of biologic treatment—from the rheumatology departments of Diakonhjemmet Hospital in Oslo and University Hospital Maastricht (the Netherlands).
Baseline measurements included calprotectin levels, erythrocyte sedimentation rates (ESRs), and C-reactive protein levels. Radiographs of the hands were obtained, and modified Sharp scores were calculated. Damage was assessed according to the RA articular damage (RAAD) score and all measurements were repeated at 10 years, Dr. Berner Hammer wrote in a poster session at the meeting, sponsored by the European League Against Rheumatism.
The 88 patients with elevated levels of calprotectin (0.9 mg/L or more) at baseline and at 10 years also had high modified Sharp and RAAD scores at both time points. (See box.)
Moreover, patients who were rheumatoid factor positive had elevated calprotectin levels as well as high ESRs, modified Sharp scores, and RAAD scores, according to Dr. Berner Hammer of Diakonhjemmet Hospital.
Calprotectin is one of the calcium-binding proinflammatory S100 proteins released during cell activation. High levels of the protein have been found in the synovial fluid of RA patients. It is also upregulated in other immunopathologic conditions, particularly in the setting of acute inflammation or Th1-mediated reactions (Physiol. Res. 2004;53:245–53). An immunoassay for the detection of fecal calprotectin in patients with inflammatory bowel disease—marketed as PhiCal by Genova Diagnostics Inc.—was recently approved by the Food and Drug Administration.
This marker has also been investigated as a measure of disease activity in polymyalgia rheumatica and temporal arteritis. A group of 47 patients, 33 with polymyalgia rheumatica, 10 with temporal arteritis, and 4 with both conditions, were followed prospectively for up to 3 years. Calprotectin was highly correlated with acute phase parameters and ESRs, and levels fell significantly after the initiation of prednisone therapy (Scand. J. Rheumatol. 2005;34:125–8).
ELSEVIER GLOBAL MEDICAL NEWS
AMSTERDAM — Baseline levels of the leukocyte protein calprotectin in patients with rheumatoid arthritis correlated with clinical and radiographic outcomes at 10 years in a prospective longitudinal study, suggesting that this biomarker may be a useful predictor of joint damage, Dr. Hilde Berner Hammer reported at the annual European Congress of Rheumatology.
A cohort of 145 patients with early rheumatoid arthritis (RA) were enrolled during 1991 and 1992—before the era of biologic treatment—from the rheumatology departments of Diakonhjemmet Hospital in Oslo and University Hospital Maastricht (the Netherlands).
Baseline measurements included calprotectin levels, erythrocyte sedimentation rates (ESRs), and C-reactive protein levels. Radiographs of the hands were obtained, and modified Sharp scores were calculated. Damage was assessed according to the RA articular damage (RAAD) score and all measurements were repeated at 10 years, Dr. Berner Hammer wrote in a poster session at the meeting, sponsored by the European League Against Rheumatism.
The 88 patients with elevated levels of calprotectin (0.9 mg/L or more) at baseline and at 10 years also had high modified Sharp and RAAD scores at both time points. (See box.)
Moreover, patients who were rheumatoid factor positive had elevated calprotectin levels as well as high ESRs, modified Sharp scores, and RAAD scores, according to Dr. Berner Hammer of Diakonhjemmet Hospital.
Calprotectin is one of the calcium-binding proinflammatory S100 proteins released during cell activation. High levels of the protein have been found in the synovial fluid of RA patients. It is also upregulated in other immunopathologic conditions, particularly in the setting of acute inflammation or Th1-mediated reactions (Physiol. Res. 2004;53:245–53). An immunoassay for the detection of fecal calprotectin in patients with inflammatory bowel disease—marketed as PhiCal by Genova Diagnostics Inc.—was recently approved by the Food and Drug Administration.
This marker has also been investigated as a measure of disease activity in polymyalgia rheumatica and temporal arteritis. A group of 47 patients, 33 with polymyalgia rheumatica, 10 with temporal arteritis, and 4 with both conditions, were followed prospectively for up to 3 years. Calprotectin was highly correlated with acute phase parameters and ESRs, and levels fell significantly after the initiation of prednisone therapy (Scand. J. Rheumatol. 2005;34:125–8).
ELSEVIER GLOBAL MEDICAL NEWS
Two Interleukin Antibodies on the RA Horizon
AMSTERDAM — Efforts to broaden the spectrum of biologic agents available for use in the treatment of rheumatoid arthritis continue, with early studies suggesting possible eventual roles for antibodies targeting two interleukins.
In a phase II study, the safety and efficacy of a human monoclonal antibody to IL-15 (AMG 714) were evaluated in 180 patients who had active rheumatoid arthritis (RA) and had failed at least one disease-modifying antirheumatic drug but who had not previously received any biologic intervention, Dr. Ian McInnes said at the annual European Congress of Rheumatology.
An initial group of 110 patients were randomized to receive the anti-IL-15 antibody in doses of 40, 80, 160, or 280 mg or placebo by subcutaneous infusion. Following a protocol amendment, an additional 70 patients were randomized to receive 280 mg or placebo every 2 weeks for 12 weeks. Efficacy was evaluated in the 114 patients who received the highest dose or placebo, with the primary end point being the proportion of patients achieving an American College of Rheumatology (ACR) 20 response at week 14.
A significantly greater number of patients receiving 280 mg of AMG 714 achieved an ACR 20 response than did those receiving placebo at week 12 (64% vs. 34%, respectively) and at week 16 (66% vs. 38%), said Dr. McInnes of the Glasgow (Scotland) Royal Infirmary.
At week 14, however, ACR 20 was achieved by 54% of the active treatment group and 38% of the placebo group, which was not a statistically significant difference.
Levels of acute phase reactants decreased significantly in the 280-mg group, compared with those on placebo, with C-reactive protein (CRP) levels remaining 50%–67% lower than in the placebo group throughout the study. “These data demonstrate pharmacologic activity of AMG 714 as indicated by the reduction of acute phase reactant levels,” Dr. McInnes said.
Serious infections were reported by one patient in the 80-mg active treatment group (sepsis) and by one patient in the placebo group (viral bronchitis).
Dr. McInnes said that although the primary efficacy end point was not met, the overall clinical results suggest that inhibiting IL-15 with this antibody may be an important treatment strategy for RA and other inflammatory conditions.
In another phase I/II proof-of-concept study conducted in 13 centers in Germany, the Netherlands, and Switzerland, the fully human anti-IL-1β monoclonal antibody ACZ885 was evaluated in 53 patients with active rheumatoid arthritis, Dr. Rieke Alten said at the meeting, sponsored by the European League Against Rheumatism.
All patients had more than six tender joints, six swollen joints, and CRP levels greater than 0.6 mg/dL or an erythrocyte sedimentation rate greater than 28 mm/h despite optimal doses of methotrexate (7.5–25 mg/week) for at least 10–12 weeks.
They were randomized to receive placebo or 0.3, 1, 3, or 10 mg/kg of the anti-IL-1β antibody, which was administered as a 2-hour intravenous infusion on days 1 and 15. Although the main objective of the study was to evaluate the pharmacokinetics and pharmacodynamics of the drug, a larger number of patients were included in the 10 mg/kg group so that some initial data on efficacy could be obtained, according to Dr. Alten of Schlosspark-Klinik, Berlin, Germany.
In the 3-mg group, 4 of 6 patients (67%) achieved ACR 20 responses, as did 6 of 19 (32%) in the 10-mg group.
In addition, in the 10-mg group, three patients (16%) and two patients (11%) reached ACR 50 and 70 responses, respectively, Dr. Alten said.
These were “important clinical improvements,” he said.
Decreases in CRP levels occurred within 1–2 weeks in all dose groups, and the duration of CRP suppression was dose dependent. No human antihuman antibodies developed on follow-up through day 112, and there were no changes in pharmacokinetics that would suggest the development of anti-ACZ885 antibodies, he said.
The infusions were well tolerated, and there were no drug-related laboratory abnormalities. Infections were limited to one case of erysipelas and one of pneumonia, both of which resolved with standard antibiotic therapy.
Studies to determine an optimal dosing regimen and characterize clinical effects in RA are warranted, Dr. Alten concluded.
AMSTERDAM — Efforts to broaden the spectrum of biologic agents available for use in the treatment of rheumatoid arthritis continue, with early studies suggesting possible eventual roles for antibodies targeting two interleukins.
In a phase II study, the safety and efficacy of a human monoclonal antibody to IL-15 (AMG 714) were evaluated in 180 patients who had active rheumatoid arthritis (RA) and had failed at least one disease-modifying antirheumatic drug but who had not previously received any biologic intervention, Dr. Ian McInnes said at the annual European Congress of Rheumatology.
An initial group of 110 patients were randomized to receive the anti-IL-15 antibody in doses of 40, 80, 160, or 280 mg or placebo by subcutaneous infusion. Following a protocol amendment, an additional 70 patients were randomized to receive 280 mg or placebo every 2 weeks for 12 weeks. Efficacy was evaluated in the 114 patients who received the highest dose or placebo, with the primary end point being the proportion of patients achieving an American College of Rheumatology (ACR) 20 response at week 14.
A significantly greater number of patients receiving 280 mg of AMG 714 achieved an ACR 20 response than did those receiving placebo at week 12 (64% vs. 34%, respectively) and at week 16 (66% vs. 38%), said Dr. McInnes of the Glasgow (Scotland) Royal Infirmary.
At week 14, however, ACR 20 was achieved by 54% of the active treatment group and 38% of the placebo group, which was not a statistically significant difference.
Levels of acute phase reactants decreased significantly in the 280-mg group, compared with those on placebo, with C-reactive protein (CRP) levels remaining 50%–67% lower than in the placebo group throughout the study. “These data demonstrate pharmacologic activity of AMG 714 as indicated by the reduction of acute phase reactant levels,” Dr. McInnes said.
Serious infections were reported by one patient in the 80-mg active treatment group (sepsis) and by one patient in the placebo group (viral bronchitis).
Dr. McInnes said that although the primary efficacy end point was not met, the overall clinical results suggest that inhibiting IL-15 with this antibody may be an important treatment strategy for RA and other inflammatory conditions.
In another phase I/II proof-of-concept study conducted in 13 centers in Germany, the Netherlands, and Switzerland, the fully human anti-IL-1β monoclonal antibody ACZ885 was evaluated in 53 patients with active rheumatoid arthritis, Dr. Rieke Alten said at the meeting, sponsored by the European League Against Rheumatism.
All patients had more than six tender joints, six swollen joints, and CRP levels greater than 0.6 mg/dL or an erythrocyte sedimentation rate greater than 28 mm/h despite optimal doses of methotrexate (7.5–25 mg/week) for at least 10–12 weeks.
They were randomized to receive placebo or 0.3, 1, 3, or 10 mg/kg of the anti-IL-1β antibody, which was administered as a 2-hour intravenous infusion on days 1 and 15. Although the main objective of the study was to evaluate the pharmacokinetics and pharmacodynamics of the drug, a larger number of patients were included in the 10 mg/kg group so that some initial data on efficacy could be obtained, according to Dr. Alten of Schlosspark-Klinik, Berlin, Germany.
In the 3-mg group, 4 of 6 patients (67%) achieved ACR 20 responses, as did 6 of 19 (32%) in the 10-mg group.
In addition, in the 10-mg group, three patients (16%) and two patients (11%) reached ACR 50 and 70 responses, respectively, Dr. Alten said.
These were “important clinical improvements,” he said.
Decreases in CRP levels occurred within 1–2 weeks in all dose groups, and the duration of CRP suppression was dose dependent. No human antihuman antibodies developed on follow-up through day 112, and there were no changes in pharmacokinetics that would suggest the development of anti-ACZ885 antibodies, he said.
The infusions were well tolerated, and there were no drug-related laboratory abnormalities. Infections were limited to one case of erysipelas and one of pneumonia, both of which resolved with standard antibiotic therapy.
Studies to determine an optimal dosing regimen and characterize clinical effects in RA are warranted, Dr. Alten concluded.
AMSTERDAM — Efforts to broaden the spectrum of biologic agents available for use in the treatment of rheumatoid arthritis continue, with early studies suggesting possible eventual roles for antibodies targeting two interleukins.
In a phase II study, the safety and efficacy of a human monoclonal antibody to IL-15 (AMG 714) were evaluated in 180 patients who had active rheumatoid arthritis (RA) and had failed at least one disease-modifying antirheumatic drug but who had not previously received any biologic intervention, Dr. Ian McInnes said at the annual European Congress of Rheumatology.
An initial group of 110 patients were randomized to receive the anti-IL-15 antibody in doses of 40, 80, 160, or 280 mg or placebo by subcutaneous infusion. Following a protocol amendment, an additional 70 patients were randomized to receive 280 mg or placebo every 2 weeks for 12 weeks. Efficacy was evaluated in the 114 patients who received the highest dose or placebo, with the primary end point being the proportion of patients achieving an American College of Rheumatology (ACR) 20 response at week 14.
A significantly greater number of patients receiving 280 mg of AMG 714 achieved an ACR 20 response than did those receiving placebo at week 12 (64% vs. 34%, respectively) and at week 16 (66% vs. 38%), said Dr. McInnes of the Glasgow (Scotland) Royal Infirmary.
At week 14, however, ACR 20 was achieved by 54% of the active treatment group and 38% of the placebo group, which was not a statistically significant difference.
Levels of acute phase reactants decreased significantly in the 280-mg group, compared with those on placebo, with C-reactive protein (CRP) levels remaining 50%–67% lower than in the placebo group throughout the study. “These data demonstrate pharmacologic activity of AMG 714 as indicated by the reduction of acute phase reactant levels,” Dr. McInnes said.
Serious infections were reported by one patient in the 80-mg active treatment group (sepsis) and by one patient in the placebo group (viral bronchitis).
Dr. McInnes said that although the primary efficacy end point was not met, the overall clinical results suggest that inhibiting IL-15 with this antibody may be an important treatment strategy for RA and other inflammatory conditions.
In another phase I/II proof-of-concept study conducted in 13 centers in Germany, the Netherlands, and Switzerland, the fully human anti-IL-1β monoclonal antibody ACZ885 was evaluated in 53 patients with active rheumatoid arthritis, Dr. Rieke Alten said at the meeting, sponsored by the European League Against Rheumatism.
All patients had more than six tender joints, six swollen joints, and CRP levels greater than 0.6 mg/dL or an erythrocyte sedimentation rate greater than 28 mm/h despite optimal doses of methotrexate (7.5–25 mg/week) for at least 10–12 weeks.
They were randomized to receive placebo or 0.3, 1, 3, or 10 mg/kg of the anti-IL-1β antibody, which was administered as a 2-hour intravenous infusion on days 1 and 15. Although the main objective of the study was to evaluate the pharmacokinetics and pharmacodynamics of the drug, a larger number of patients were included in the 10 mg/kg group so that some initial data on efficacy could be obtained, according to Dr. Alten of Schlosspark-Klinik, Berlin, Germany.
In the 3-mg group, 4 of 6 patients (67%) achieved ACR 20 responses, as did 6 of 19 (32%) in the 10-mg group.
In addition, in the 10-mg group, three patients (16%) and two patients (11%) reached ACR 50 and 70 responses, respectively, Dr. Alten said.
These were “important clinical improvements,” he said.
Decreases in CRP levels occurred within 1–2 weeks in all dose groups, and the duration of CRP suppression was dose dependent. No human antihuman antibodies developed on follow-up through day 112, and there were no changes in pharmacokinetics that would suggest the development of anti-ACZ885 antibodies, he said.
The infusions were well tolerated, and there were no drug-related laboratory abnormalities. Infections were limited to one case of erysipelas and one of pneumonia, both of which resolved with standard antibiotic therapy.
Studies to determine an optimal dosing regimen and characterize clinical effects in RA are warranted, Dr. Alten concluded.
New Link Is Found Between Psoriasis and Heart Disease
MANCHESTER, ENGLAND — The latest piece of evidence linking psoriasis with cardiovascular disease suggests that patients with the skin disease are at high risk of having elevated serum levels of homocysteine, Dr. Anne-Marie Tobin said at the annual meeting of the British Association of Dermatologists.
In the general population, hyperhomocysteinemia has been shown to be an independent risk factor for the development of cardiovascular disease, with a magnitude of risk similar to that of smoking and hyperlipidemia. Elevated levels of homocysteine have been linked to atherosclerosis, endothelial damage, and thrombogenesis.
Cardiovascular disease is the leading cause of mortality among patients with psoriasis. The precise reasons why patients with psoriasis are at risk for cardiovascular disease remain unclear, although several possible contributory factors exist. Some of the excess cardiovascular risk may relate to increased rates of smoking and hypertension, risk factors that have been documented in this patient population.
“Moreover, there has been a suggestion from the rheumatology literature that chronic inflammation elevates cardiovascular risk, although this has yet to be confirmed in psoriasis,” said Dr. Tobin of the department of dermatology, Adelaide and Meath Hospital, Incorporating the National Children's Hospital, Dublin.
Patients with psoriasis also have raised levels of lipoprotein A, which further increases risk for coronary heart disease and ischemic stroke. Moreover, small uncontrolled studies have suggested patients with psoriasis may have low levels of folate, which helps break down homocysteine. The accelerated rate of keratinocyte turnover seen in psoriasis is thought to lower levels of folate, she said.
“Based on these observations, we undertook a study to assess homocysteine levels in outpatients with moderate to severe psoriasis who were not on systemic treatment, and to assess the homocysteine levels in the context of major conventional cardiovascular risk factors,” Dr. Tobin said.
Twenty patients, of whom 11 were women, were recruited. Mean age was 42 years, and mean Psoriasis Area and Severity Index (PASI) was 12.8. Twenty age- and sex-matched controls were also enrolled. The patients were evaluated for body mass index (BMI), blood pressure, and levels of glucose, lipids, homocysteine, and folate.
One patient with psoriasis had extremely low levels of folate and also had atrophic gastritis and pernicious anemia and was excluded from further analysis.
Five patients with psoriasis had homocysteine levels of 12 μmol/L or higher, compared with only one control subject. Population-based studies suggest that slightly more than 5% of the general population has elevated homocysteine, which was similar to the figure for the controls in this study. “But with more than 27% of our patients with psoriasis having raised levels of homocysteine, the odds ratio of their having hyperhomocysteinemia was greater than 7,” compared with controls, Dr. Tobin reported.
There was no correlation between levels of homocysteine and PASI. Patients with psoriasis also had a trend for low levels of red-cell folate, but this was not statistically significant. “Hyperhomocysteinemia was not related to either folate status or disease severity in psoriasis patients, as had been supposed,” she said.
Likelihood of high BMI also was increased among psoriasis patients: A total of 17 patients with psoriasis had a BMI greater than 25, compared with only 4 controls. Three of the 17 were clinically obese and 2 were morbidly obese, she noted.
Patients with psoriasis also had significantly raised systolic blood pressure. “However, because diastolic blood pressure was normal and the fact that blood pressure readings were not repeated, we were unsure of the significance of this result,” Dr. Tobin said. She said the significance of the results warrants a large population-based study to identify the risk factors that should be routinely measured in patients with psoriasis.
MANCHESTER, ENGLAND — The latest piece of evidence linking psoriasis with cardiovascular disease suggests that patients with the skin disease are at high risk of having elevated serum levels of homocysteine, Dr. Anne-Marie Tobin said at the annual meeting of the British Association of Dermatologists.
In the general population, hyperhomocysteinemia has been shown to be an independent risk factor for the development of cardiovascular disease, with a magnitude of risk similar to that of smoking and hyperlipidemia. Elevated levels of homocysteine have been linked to atherosclerosis, endothelial damage, and thrombogenesis.
Cardiovascular disease is the leading cause of mortality among patients with psoriasis. The precise reasons why patients with psoriasis are at risk for cardiovascular disease remain unclear, although several possible contributory factors exist. Some of the excess cardiovascular risk may relate to increased rates of smoking and hypertension, risk factors that have been documented in this patient population.
“Moreover, there has been a suggestion from the rheumatology literature that chronic inflammation elevates cardiovascular risk, although this has yet to be confirmed in psoriasis,” said Dr. Tobin of the department of dermatology, Adelaide and Meath Hospital, Incorporating the National Children's Hospital, Dublin.
Patients with psoriasis also have raised levels of lipoprotein A, which further increases risk for coronary heart disease and ischemic stroke. Moreover, small uncontrolled studies have suggested patients with psoriasis may have low levels of folate, which helps break down homocysteine. The accelerated rate of keratinocyte turnover seen in psoriasis is thought to lower levels of folate, she said.
“Based on these observations, we undertook a study to assess homocysteine levels in outpatients with moderate to severe psoriasis who were not on systemic treatment, and to assess the homocysteine levels in the context of major conventional cardiovascular risk factors,” Dr. Tobin said.
Twenty patients, of whom 11 were women, were recruited. Mean age was 42 years, and mean Psoriasis Area and Severity Index (PASI) was 12.8. Twenty age- and sex-matched controls were also enrolled. The patients were evaluated for body mass index (BMI), blood pressure, and levels of glucose, lipids, homocysteine, and folate.
One patient with psoriasis had extremely low levels of folate and also had atrophic gastritis and pernicious anemia and was excluded from further analysis.
Five patients with psoriasis had homocysteine levels of 12 μmol/L or higher, compared with only one control subject. Population-based studies suggest that slightly more than 5% of the general population has elevated homocysteine, which was similar to the figure for the controls in this study. “But with more than 27% of our patients with psoriasis having raised levels of homocysteine, the odds ratio of their having hyperhomocysteinemia was greater than 7,” compared with controls, Dr. Tobin reported.
There was no correlation between levels of homocysteine and PASI. Patients with psoriasis also had a trend for low levels of red-cell folate, but this was not statistically significant. “Hyperhomocysteinemia was not related to either folate status or disease severity in psoriasis patients, as had been supposed,” she said.
Likelihood of high BMI also was increased among psoriasis patients: A total of 17 patients with psoriasis had a BMI greater than 25, compared with only 4 controls. Three of the 17 were clinically obese and 2 were morbidly obese, she noted.
Patients with psoriasis also had significantly raised systolic blood pressure. “However, because diastolic blood pressure was normal and the fact that blood pressure readings were not repeated, we were unsure of the significance of this result,” Dr. Tobin said. She said the significance of the results warrants a large population-based study to identify the risk factors that should be routinely measured in patients with psoriasis.
MANCHESTER, ENGLAND — The latest piece of evidence linking psoriasis with cardiovascular disease suggests that patients with the skin disease are at high risk of having elevated serum levels of homocysteine, Dr. Anne-Marie Tobin said at the annual meeting of the British Association of Dermatologists.
In the general population, hyperhomocysteinemia has been shown to be an independent risk factor for the development of cardiovascular disease, with a magnitude of risk similar to that of smoking and hyperlipidemia. Elevated levels of homocysteine have been linked to atherosclerosis, endothelial damage, and thrombogenesis.
Cardiovascular disease is the leading cause of mortality among patients with psoriasis. The precise reasons why patients with psoriasis are at risk for cardiovascular disease remain unclear, although several possible contributory factors exist. Some of the excess cardiovascular risk may relate to increased rates of smoking and hypertension, risk factors that have been documented in this patient population.
“Moreover, there has been a suggestion from the rheumatology literature that chronic inflammation elevates cardiovascular risk, although this has yet to be confirmed in psoriasis,” said Dr. Tobin of the department of dermatology, Adelaide and Meath Hospital, Incorporating the National Children's Hospital, Dublin.
Patients with psoriasis also have raised levels of lipoprotein A, which further increases risk for coronary heart disease and ischemic stroke. Moreover, small uncontrolled studies have suggested patients with psoriasis may have low levels of folate, which helps break down homocysteine. The accelerated rate of keratinocyte turnover seen in psoriasis is thought to lower levels of folate, she said.
“Based on these observations, we undertook a study to assess homocysteine levels in outpatients with moderate to severe psoriasis who were not on systemic treatment, and to assess the homocysteine levels in the context of major conventional cardiovascular risk factors,” Dr. Tobin said.
Twenty patients, of whom 11 were women, were recruited. Mean age was 42 years, and mean Psoriasis Area and Severity Index (PASI) was 12.8. Twenty age- and sex-matched controls were also enrolled. The patients were evaluated for body mass index (BMI), blood pressure, and levels of glucose, lipids, homocysteine, and folate.
One patient with psoriasis had extremely low levels of folate and also had atrophic gastritis and pernicious anemia and was excluded from further analysis.
Five patients with psoriasis had homocysteine levels of 12 μmol/L or higher, compared with only one control subject. Population-based studies suggest that slightly more than 5% of the general population has elevated homocysteine, which was similar to the figure for the controls in this study. “But with more than 27% of our patients with psoriasis having raised levels of homocysteine, the odds ratio of their having hyperhomocysteinemia was greater than 7,” compared with controls, Dr. Tobin reported.
There was no correlation between levels of homocysteine and PASI. Patients with psoriasis also had a trend for low levels of red-cell folate, but this was not statistically significant. “Hyperhomocysteinemia was not related to either folate status or disease severity in psoriasis patients, as had been supposed,” she said.
Likelihood of high BMI also was increased among psoriasis patients: A total of 17 patients with psoriasis had a BMI greater than 25, compared with only 4 controls. Three of the 17 were clinically obese and 2 were morbidly obese, she noted.
Patients with psoriasis also had significantly raised systolic blood pressure. “However, because diastolic blood pressure was normal and the fact that blood pressure readings were not repeated, we were unsure of the significance of this result,” Dr. Tobin said. She said the significance of the results warrants a large population-based study to identify the risk factors that should be routinely measured in patients with psoriasis.
Merkel Cell Raises the Risk of Other Tumors
MANCHESTER, ENGLAND — Patients with Merkel cell carcinoma are at high risk for multiple malignancies and should be closely examined at the time of diagnosis for other possible tumors, Dr. Julia K. Gass said at the annual meeting of the British Association of Dermatologists.
A review of the data of all 27 cases of Merkel cell carcinoma treated at Addenbrooke's Hospital National Health Service Trust, Cambridge, England, between 1995 and 2004 found additional tumors in 70% of cases, she said. The patients were elderly, with a mean age of 78 years. A total of 44% of these patients had one other tumor, 22% had three, and 4% had four additional malignancies.
Using information from the Eastern Region Cancer Registry, the rate of multiple malignancies was compared with that in the background population. When adjusted for advanced age, an incidence ratio of 3.47 was found, said Dr. Gass of Addenbrooke's dermatology department. Additional malignancies were cutaneous in 18 patients. Two of these were melanomas, seven were squamous cell carcinomas, and nine were basal cell.
An association of squamous cell carcinoma with Merkel cell carcinoma has been noted previously. Mixed tumors have also been seen, leading to the hypothesis that both types of tumor arise from a pluripotential epidermal stem cell damaged by ultraviolet light. Supporting the role of UV light in the pathogenesis of Merkel and squamous cell carcinomas is the finding that some of these tumors share UVB-type specific mutations of the p53 tumor suppressor gene and the Harvey-ras oncogene, she said.
The noncutaneous tumors in these patients included colorectal cancer in five, hematologic malignancies in three, and a breast tumor in one. The rare phenomenon of synchronous metastases from a Merkel cell carcinoma and from a second tumor to the same lymph node was seen in two patients, one with chronic lymphocytic leukemia and one with breast cancer. The synchronous metastasis of Merkel cell carcinomas and B-cell tumors, such as chronic lymphocytic leukemia, has previously been reported and may relate to genetic susceptibility, advanced age, immunosuppression by one tumor, or a common inducing agent.
MANCHESTER, ENGLAND — Patients with Merkel cell carcinoma are at high risk for multiple malignancies and should be closely examined at the time of diagnosis for other possible tumors, Dr. Julia K. Gass said at the annual meeting of the British Association of Dermatologists.
A review of the data of all 27 cases of Merkel cell carcinoma treated at Addenbrooke's Hospital National Health Service Trust, Cambridge, England, between 1995 and 2004 found additional tumors in 70% of cases, she said. The patients were elderly, with a mean age of 78 years. A total of 44% of these patients had one other tumor, 22% had three, and 4% had four additional malignancies.
Using information from the Eastern Region Cancer Registry, the rate of multiple malignancies was compared with that in the background population. When adjusted for advanced age, an incidence ratio of 3.47 was found, said Dr. Gass of Addenbrooke's dermatology department. Additional malignancies were cutaneous in 18 patients. Two of these were melanomas, seven were squamous cell carcinomas, and nine were basal cell.
An association of squamous cell carcinoma with Merkel cell carcinoma has been noted previously. Mixed tumors have also been seen, leading to the hypothesis that both types of tumor arise from a pluripotential epidermal stem cell damaged by ultraviolet light. Supporting the role of UV light in the pathogenesis of Merkel and squamous cell carcinomas is the finding that some of these tumors share UVB-type specific mutations of the p53 tumor suppressor gene and the Harvey-ras oncogene, she said.
The noncutaneous tumors in these patients included colorectal cancer in five, hematologic malignancies in three, and a breast tumor in one. The rare phenomenon of synchronous metastases from a Merkel cell carcinoma and from a second tumor to the same lymph node was seen in two patients, one with chronic lymphocytic leukemia and one with breast cancer. The synchronous metastasis of Merkel cell carcinomas and B-cell tumors, such as chronic lymphocytic leukemia, has previously been reported and may relate to genetic susceptibility, advanced age, immunosuppression by one tumor, or a common inducing agent.
MANCHESTER, ENGLAND — Patients with Merkel cell carcinoma are at high risk for multiple malignancies and should be closely examined at the time of diagnosis for other possible tumors, Dr. Julia K. Gass said at the annual meeting of the British Association of Dermatologists.
A review of the data of all 27 cases of Merkel cell carcinoma treated at Addenbrooke's Hospital National Health Service Trust, Cambridge, England, between 1995 and 2004 found additional tumors in 70% of cases, she said. The patients were elderly, with a mean age of 78 years. A total of 44% of these patients had one other tumor, 22% had three, and 4% had four additional malignancies.
Using information from the Eastern Region Cancer Registry, the rate of multiple malignancies was compared with that in the background population. When adjusted for advanced age, an incidence ratio of 3.47 was found, said Dr. Gass of Addenbrooke's dermatology department. Additional malignancies were cutaneous in 18 patients. Two of these were melanomas, seven were squamous cell carcinomas, and nine were basal cell.
An association of squamous cell carcinoma with Merkel cell carcinoma has been noted previously. Mixed tumors have also been seen, leading to the hypothesis that both types of tumor arise from a pluripotential epidermal stem cell damaged by ultraviolet light. Supporting the role of UV light in the pathogenesis of Merkel and squamous cell carcinomas is the finding that some of these tumors share UVB-type specific mutations of the p53 tumor suppressor gene and the Harvey-ras oncogene, she said.
The noncutaneous tumors in these patients included colorectal cancer in five, hematologic malignancies in three, and a breast tumor in one. The rare phenomenon of synchronous metastases from a Merkel cell carcinoma and from a second tumor to the same lymph node was seen in two patients, one with chronic lymphocytic leukemia and one with breast cancer. The synchronous metastasis of Merkel cell carcinomas and B-cell tumors, such as chronic lymphocytic leukemia, has previously been reported and may relate to genetic susceptibility, advanced age, immunosuppression by one tumor, or a common inducing agent.
Injectable MTX Better Than Oral Form for RA
AMSTERDAM — In the first direct comparison of oral versus subcutaneous methotrexate for patients with active rheumatoid arthritis, the injectable formulation was significantly more effective, Dr. Jürgen Braun said at the annual European Congress of Rheumatology.
The multicenter study involved 384 patients, none of whom had previously taken methotrexate (MTX) or biologics. They were predominantly female. Mean age was 59 and mean time since diagnosis was 2 months, said Dr. Braun of Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany.
They were randomized to 15 mg oral MTX plus placebo injections or injectable MTX in the same dose plus dummy pills, once weekly, for 24 weeks. At week 16, patients receiving oral MTX could be switched to subcutaneous, and those receiving the injectable drug could have a dosage increase to 20 mg, he said.
A total of 78% of patients on subcutaneous MTX met the primary efficacy outcome of ACR20 response at 24 weeks, compared with 67% of those on oral MTX, Dr. Braun reported at the meeting, sponsored by the European League Against Rheumatism. This difference was statistically significant, as was the difference in percentages achieving ACR70 responses (43% vs. 31%, respectively).
Remission, defined as a Disease Activity Score 28 less than 2.6, was reached by 34% of patients on the subcutaneous formulation, compared with only 24% of those on the oral drug, a statistically significant difference.
AMSTERDAM — In the first direct comparison of oral versus subcutaneous methotrexate for patients with active rheumatoid arthritis, the injectable formulation was significantly more effective, Dr. Jürgen Braun said at the annual European Congress of Rheumatology.
The multicenter study involved 384 patients, none of whom had previously taken methotrexate (MTX) or biologics. They were predominantly female. Mean age was 59 and mean time since diagnosis was 2 months, said Dr. Braun of Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany.
They were randomized to 15 mg oral MTX plus placebo injections or injectable MTX in the same dose plus dummy pills, once weekly, for 24 weeks. At week 16, patients receiving oral MTX could be switched to subcutaneous, and those receiving the injectable drug could have a dosage increase to 20 mg, he said.
A total of 78% of patients on subcutaneous MTX met the primary efficacy outcome of ACR20 response at 24 weeks, compared with 67% of those on oral MTX, Dr. Braun reported at the meeting, sponsored by the European League Against Rheumatism. This difference was statistically significant, as was the difference in percentages achieving ACR70 responses (43% vs. 31%, respectively).
Remission, defined as a Disease Activity Score 28 less than 2.6, was reached by 34% of patients on the subcutaneous formulation, compared with only 24% of those on the oral drug, a statistically significant difference.
AMSTERDAM — In the first direct comparison of oral versus subcutaneous methotrexate for patients with active rheumatoid arthritis, the injectable formulation was significantly more effective, Dr. Jürgen Braun said at the annual European Congress of Rheumatology.
The multicenter study involved 384 patients, none of whom had previously taken methotrexate (MTX) or biologics. They were predominantly female. Mean age was 59 and mean time since diagnosis was 2 months, said Dr. Braun of Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany.
They were randomized to 15 mg oral MTX plus placebo injections or injectable MTX in the same dose plus dummy pills, once weekly, for 24 weeks. At week 16, patients receiving oral MTX could be switched to subcutaneous, and those receiving the injectable drug could have a dosage increase to 20 mg, he said.
A total of 78% of patients on subcutaneous MTX met the primary efficacy outcome of ACR20 response at 24 weeks, compared with 67% of those on oral MTX, Dr. Braun reported at the meeting, sponsored by the European League Against Rheumatism. This difference was statistically significant, as was the difference in percentages achieving ACR70 responses (43% vs. 31%, respectively).
Remission, defined as a Disease Activity Score 28 less than 2.6, was reached by 34% of patients on the subcutaneous formulation, compared with only 24% of those on the oral drug, a statistically significant difference.
Tocilizumab Found to Provide Rapid JIA Improvement, Relief
AMSTERDAM — In the first double-blind study evaluating tocilizumab in refractory systemic juvenile idiopathic arthritis, rapid and substantial improvements were seen, suggesting that interleukin-6 blockade is one of the most promising approaches for this condition, Dr. Shumpei Yokota said at the annual European Congress of Rheumatology.
A group of 56 patients with systemic juvenile idiopathic arthritis (JIA) diagnosed according to the criteria of the International League of Associations for Rheumatology were included in the multicenter Japanese study. A total of 62.5% (35) of the patients were female. Their mean age was 8.3 years, and mean disease duration was 4.5 years.
Interleukin (IL)-6 levels were high at baseline, at a mean level of 37.2 pg/mL.
Because this was a pediatric study, there was an initial 6-week lead-in period during which all patients received the active treatment of 8 mg/kg tocilizumab every other week. At the end of this phase, those who responded were randomized to active treatment on the same schedule or placebo for up to 12 weeks.
For patients receiving placebo who flared, the drug was reinstituted as soon as possible said Dr. Yokota of the department of pediatrics, Yokohama City (Japan) University.
At the end of the 6-week open phase of the trial, the JIA core set of responses among the 56 patients were as follows: 51 achieved 30% improvement, 48 achieved 50% improvement, and 38 achieved 70% improvement. Consistent improvements were seen in each core set variable, Dr. Yokota said.
Six patients withdrew during the lead-in phase of the study, and six others were not randomized because their C-reactive protein levels remained high. An additional patient was not considered evaluable because of inadvertent unmasking of the code. During the 12-week double-blind phase, 19 of 23 (82.6%) patients receiving placebo had a flare and were withdrawn, compared with 4 of 20 (20.0%) of those receiving the IL-6 blocker.
In other words, flare was prevented in 80% of the tocilizumab group and in only 17.4% of those in the placebo group, Dr. Yokota said. In addition, JIA-70 responses were seen in 85% of the tocilizumab group, compared with 35% of the placebo group.
One patient in each group withdrew because of adverse events. One patient experienced anaphylactic shock following the second infusion of tocilizumab, and one had a gastrointestinal hemorrhage, probably relating to long-term use of systemic corticosteroids, the investigator noted. The drug was generally well tolerated for periods of up to 18 weeks. Nonetheless, patients undergoing treatment with tocilizumab should be closely monitored, Dr. Yokota said.
AMSTERDAM — In the first double-blind study evaluating tocilizumab in refractory systemic juvenile idiopathic arthritis, rapid and substantial improvements were seen, suggesting that interleukin-6 blockade is one of the most promising approaches for this condition, Dr. Shumpei Yokota said at the annual European Congress of Rheumatology.
A group of 56 patients with systemic juvenile idiopathic arthritis (JIA) diagnosed according to the criteria of the International League of Associations for Rheumatology were included in the multicenter Japanese study. A total of 62.5% (35) of the patients were female. Their mean age was 8.3 years, and mean disease duration was 4.5 years.
Interleukin (IL)-6 levels were high at baseline, at a mean level of 37.2 pg/mL.
Because this was a pediatric study, there was an initial 6-week lead-in period during which all patients received the active treatment of 8 mg/kg tocilizumab every other week. At the end of this phase, those who responded were randomized to active treatment on the same schedule or placebo for up to 12 weeks.
For patients receiving placebo who flared, the drug was reinstituted as soon as possible said Dr. Yokota of the department of pediatrics, Yokohama City (Japan) University.
At the end of the 6-week open phase of the trial, the JIA core set of responses among the 56 patients were as follows: 51 achieved 30% improvement, 48 achieved 50% improvement, and 38 achieved 70% improvement. Consistent improvements were seen in each core set variable, Dr. Yokota said.
Six patients withdrew during the lead-in phase of the study, and six others were not randomized because their C-reactive protein levels remained high. An additional patient was not considered evaluable because of inadvertent unmasking of the code. During the 12-week double-blind phase, 19 of 23 (82.6%) patients receiving placebo had a flare and were withdrawn, compared with 4 of 20 (20.0%) of those receiving the IL-6 blocker.
In other words, flare was prevented in 80% of the tocilizumab group and in only 17.4% of those in the placebo group, Dr. Yokota said. In addition, JIA-70 responses were seen in 85% of the tocilizumab group, compared with 35% of the placebo group.
One patient in each group withdrew because of adverse events. One patient experienced anaphylactic shock following the second infusion of tocilizumab, and one had a gastrointestinal hemorrhage, probably relating to long-term use of systemic corticosteroids, the investigator noted. The drug was generally well tolerated for periods of up to 18 weeks. Nonetheless, patients undergoing treatment with tocilizumab should be closely monitored, Dr. Yokota said.
AMSTERDAM — In the first double-blind study evaluating tocilizumab in refractory systemic juvenile idiopathic arthritis, rapid and substantial improvements were seen, suggesting that interleukin-6 blockade is one of the most promising approaches for this condition, Dr. Shumpei Yokota said at the annual European Congress of Rheumatology.
A group of 56 patients with systemic juvenile idiopathic arthritis (JIA) diagnosed according to the criteria of the International League of Associations for Rheumatology were included in the multicenter Japanese study. A total of 62.5% (35) of the patients were female. Their mean age was 8.3 years, and mean disease duration was 4.5 years.
Interleukin (IL)-6 levels were high at baseline, at a mean level of 37.2 pg/mL.
Because this was a pediatric study, there was an initial 6-week lead-in period during which all patients received the active treatment of 8 mg/kg tocilizumab every other week. At the end of this phase, those who responded were randomized to active treatment on the same schedule or placebo for up to 12 weeks.
For patients receiving placebo who flared, the drug was reinstituted as soon as possible said Dr. Yokota of the department of pediatrics, Yokohama City (Japan) University.
At the end of the 6-week open phase of the trial, the JIA core set of responses among the 56 patients were as follows: 51 achieved 30% improvement, 48 achieved 50% improvement, and 38 achieved 70% improvement. Consistent improvements were seen in each core set variable, Dr. Yokota said.
Six patients withdrew during the lead-in phase of the study, and six others were not randomized because their C-reactive protein levels remained high. An additional patient was not considered evaluable because of inadvertent unmasking of the code. During the 12-week double-blind phase, 19 of 23 (82.6%) patients receiving placebo had a flare and were withdrawn, compared with 4 of 20 (20.0%) of those receiving the IL-6 blocker.
In other words, flare was prevented in 80% of the tocilizumab group and in only 17.4% of those in the placebo group, Dr. Yokota said. In addition, JIA-70 responses were seen in 85% of the tocilizumab group, compared with 35% of the placebo group.
One patient in each group withdrew because of adverse events. One patient experienced anaphylactic shock following the second infusion of tocilizumab, and one had a gastrointestinal hemorrhage, probably relating to long-term use of systemic corticosteroids, the investigator noted. The drug was generally well tolerated for periods of up to 18 weeks. Nonetheless, patients undergoing treatment with tocilizumab should be closely monitored, Dr. Yokota said.