Low-Dose Infliximab Effective In Active Ankylosing Spondylitis

MONT TREMBLANT, QUE. — Low-dose infliximab effectively reduced the signs and symptoms of active ankylosing spondylitis over 12 weeks in a double-blind, placebo-controlled trial, and response was maintained in a small group through 50 weeks, according to data from a randomized controlled trial.

In ankylosing spondylitis (AS), infliximab is generally given in doses of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks. If the drug could be given in 3 mg/kg, as is the case in rheumatoid arthritis, patients and the health care system stand to save a substantial amount of money, Dr. Robert D. Inman reported at the annual meeting of the Canadian Rheumatology Association.

In the CANDLE (Canadian Evaluation of Low-Dose Infliximab in Ankylosing Spondylitis) trial, 76 patients aged 18 years and older were randomized to receive a 3-mg/kg dose of infliximab or placebo intravenously at weeks 0, 2, and 6. The primary end point was the proportion of patients achieving an ASAS (Assessment in Ankylosing Spondylitis Working Group) 20 response at week 12.

About 80% of patients were male. Mean time since the first symptoms appeared was 19 years, and mean time since diagnosis was 11 years. In all, 73% were HLA B27 positive, approximately 10% had a history of inflammatory bowel disease, 34% had a history of uveitis, and 7% had a history of psoriasis.

At week 12, the percentage of patients achieving an ASAS 20 score was 54% in patients receiving infliximab versus 31% in patients receiving placebo.

Additionally, 41% and 21% of infliximab patients achieved ASAS 50 and ASAS 70 responses, respectively, compared with 6% and none of the placebo patients, according to poster presentation results presented by Dr. Inman, professor of medicine and immunology at the University of Toronto.

At week 12, the blind was broken and the infliximab group continued to receive the active treatment, while patients originally in the placebo group began infliximab therapy (3 mg/kg) at weeks 16, 18, 22, and every 8 weeks until week 46.

By week 50, 83% of patients in the original infliximab group and 80% of those who had been randomized to placebo but subsequently switched to the active drug had achieved an ASAS 20 response.

Additionally, 64% and 28% of the original infliximab group had achieved ASAS 50 and 70 responses, respectively, as had 69% and 40% of the original placebo group.

At week 12, patients in the infliximab group reported greater improvement in various domains of the Medical Outcomes Study SF-36 (short form-36), including body pain, vitality, social functioning, and mental health, and significant improvements in all eight domains were reported at weeks 22 and 50.

Most of the adverse events reported in the study were classified as unlikely to be related to the study medication. Only one patient discontinued the study because of an adverse event, Dr. Inman noted.

During the unblinded phase of the study, patients with an inadequate clinical response were permitted to have an increase in dose to 5 mg/kg. At week 22, 38% of patients previously in the placebo group required dose titration, as did 62% of those in the infliximab group.

By week 38, 67% of patients previously in the placebo group and 84% of those in the infliximab group required an increase in their infliximab dose, according to Dr. Inman, who dislcosed that he has served as consultant to Schering-Plough Corp., the study sponsor.

Although most patients did need the higher dose over time, a subset of patients will respond to induction and maintain response at 50 weeks with low-dose infliximab, Dr. Inman wrote.

A subanalysis in CANDLE included 32 patients who underwent spinal MRI at baseline and 12 weeks to evaluate the effects of low-dose infliximab on spinal inflammation as measured by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI index.

At baseline, the mean SPARCC score was 18.03 in the placebo group and 17.63 in the infliximab group. Three patients had no spinal inflammation evidence at baseline.

At week 12, the mean SPARCC score remained at 18.03 in the placebo group but fell to a mean of 6.22 in the infliximab group, which was a statistically significant difference.

MONT TREMBLANT, QUE. — Low-dose infliximab effectively reduced the signs and symptoms of active ankylosing spondylitis over 12 weeks in a double-blind, placebo-controlled trial, and response was maintained in a small group through 50 weeks, according to data from a randomized controlled trial.

In ankylosing spondylitis (AS), infliximab is generally given in doses of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks. If the drug could be given in 3 mg/kg, as is the case in rheumatoid arthritis, patients and the health care system stand to save a substantial amount of money, Dr. Robert D. Inman reported at the annual meeting of the Canadian Rheumatology Association.

In the CANDLE (Canadian Evaluation of Low-Dose Infliximab in Ankylosing Spondylitis) trial, 76 patients aged 18 years and older were randomized to receive a 3-mg/kg dose of infliximab or placebo intravenously at weeks 0, 2, and 6. The primary end point was the proportion of patients achieving an ASAS (Assessment in Ankylosing Spondylitis Working Group) 20 response at week 12.

About 80% of patients were male. Mean time since the first symptoms appeared was 19 years, and mean time since diagnosis was 11 years. In all, 73% were HLA B27 positive, approximately 10% had a history of inflammatory bowel disease, 34% had a history of uveitis, and 7% had a history of psoriasis.

At week 12, the percentage of patients achieving an ASAS 20 score was 54% in patients receiving infliximab versus 31% in patients receiving placebo.

Additionally, 41% and 21% of infliximab patients achieved ASAS 50 and ASAS 70 responses, respectively, compared with 6% and none of the placebo patients, according to poster presentation results presented by Dr. Inman, professor of medicine and immunology at the University of Toronto.

At week 12, the blind was broken and the infliximab group continued to receive the active treatment, while patients originally in the placebo group began infliximab therapy (3 mg/kg) at weeks 16, 18, 22, and every 8 weeks until week 46.

By week 50, 83% of patients in the original infliximab group and 80% of those who had been randomized to placebo but subsequently switched to the active drug had achieved an ASAS 20 response.

Additionally, 64% and 28% of the original infliximab group had achieved ASAS 50 and 70 responses, respectively, as had 69% and 40% of the original placebo group.

At week 12, patients in the infliximab group reported greater improvement in various domains of the Medical Outcomes Study SF-36 (short form-36), including body pain, vitality, social functioning, and mental health, and significant improvements in all eight domains were reported at weeks 22 and 50.

Most of the adverse events reported in the study were classified as unlikely to be related to the study medication. Only one patient discontinued the study because of an adverse event, Dr. Inman noted.

During the unblinded phase of the study, patients with an inadequate clinical response were permitted to have an increase in dose to 5 mg/kg. At week 22, 38% of patients previously in the placebo group required dose titration, as did 62% of those in the infliximab group.

By week 38, 67% of patients previously in the placebo group and 84% of those in the infliximab group required an increase in their infliximab dose, according to Dr. Inman, who dislcosed that he has served as consultant to Schering-Plough Corp., the study sponsor.

Although most patients did need the higher dose over time, a subset of patients will respond to induction and maintain response at 50 weeks with low-dose infliximab, Dr. Inman wrote.

A subanalysis in CANDLE included 32 patients who underwent spinal MRI at baseline and 12 weeks to evaluate the effects of low-dose infliximab on spinal inflammation as measured by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI index.

At baseline, the mean SPARCC score was 18.03 in the placebo group and 17.63 in the infliximab group. Three patients had no spinal inflammation evidence at baseline.

At week 12, the mean SPARCC score remained at 18.03 in the placebo group but fell to a mean of 6.22 in the infliximab group, which was a statistically significant difference.

MONT TREMBLANT, QUE. — Low-dose infliximab effectively reduced the signs and symptoms of active ankylosing spondylitis over 12 weeks in a double-blind, placebo-controlled trial, and response was maintained in a small group through 50 weeks, according to data from a randomized controlled trial.

In ankylosing spondylitis (AS), infliximab is generally given in doses of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks. If the drug could be given in 3 mg/kg, as is the case in rheumatoid arthritis, patients and the health care system stand to save a substantial amount of money, Dr. Robert D. Inman reported at the annual meeting of the Canadian Rheumatology Association.

In the CANDLE (Canadian Evaluation of Low-Dose Infliximab in Ankylosing Spondylitis) trial, 76 patients aged 18 years and older were randomized to receive a 3-mg/kg dose of infliximab or placebo intravenously at weeks 0, 2, and 6. The primary end point was the proportion of patients achieving an ASAS (Assessment in Ankylosing Spondylitis Working Group) 20 response at week 12.

About 80% of patients were male. Mean time since the first symptoms appeared was 19 years, and mean time since diagnosis was 11 years. In all, 73% were HLA B27 positive, approximately 10% had a history of inflammatory bowel disease, 34% had a history of uveitis, and 7% had a history of psoriasis.

At week 12, the percentage of patients achieving an ASAS 20 score was 54% in patients receiving infliximab versus 31% in patients receiving placebo.

Additionally, 41% and 21% of infliximab patients achieved ASAS 50 and ASAS 70 responses, respectively, compared with 6% and none of the placebo patients, according to poster presentation results presented by Dr. Inman, professor of medicine and immunology at the University of Toronto.

At week 12, the blind was broken and the infliximab group continued to receive the active treatment, while patients originally in the placebo group began infliximab therapy (3 mg/kg) at weeks 16, 18, 22, and every 8 weeks until week 46.

By week 50, 83% of patients in the original infliximab group and 80% of those who had been randomized to placebo but subsequently switched to the active drug had achieved an ASAS 20 response.

Additionally, 64% and 28% of the original infliximab group had achieved ASAS 50 and 70 responses, respectively, as had 69% and 40% of the original placebo group.

At week 12, patients in the infliximab group reported greater improvement in various domains of the Medical Outcomes Study SF-36 (short form-36), including body pain, vitality, social functioning, and mental health, and significant improvements in all eight domains were reported at weeks 22 and 50.

Most of the adverse events reported in the study were classified as unlikely to be related to the study medication. Only one patient discontinued the study because of an adverse event, Dr. Inman noted.

During the unblinded phase of the study, patients with an inadequate clinical response were permitted to have an increase in dose to 5 mg/kg. At week 22, 38% of patients previously in the placebo group required dose titration, as did 62% of those in the infliximab group.

By week 38, 67% of patients previously in the placebo group and 84% of those in the infliximab group required an increase in their infliximab dose, according to Dr. Inman, who dislcosed that he has served as consultant to Schering-Plough Corp., the study sponsor.

Although most patients did need the higher dose over time, a subset of patients will respond to induction and maintain response at 50 weeks with low-dose infliximab, Dr. Inman wrote.

A subanalysis in CANDLE included 32 patients who underwent spinal MRI at baseline and 12 weeks to evaluate the effects of low-dose infliximab on spinal inflammation as measured by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI index.

At baseline, the mean SPARCC score was 18.03 in the placebo group and 17.63 in the infliximab group. Three patients had no spinal inflammation evidence at baseline.

At week 12, the mean SPARCC score remained at 18.03 in the placebo group but fell to a mean of 6.22 in the infliximab group, which was a statistically significant difference.