Rituximab Effective for Rheumatoid Arthritis in Real World Use

LIVERPOOL, ENGLAND — Rituximab has been used successfully in a real-world setting as a first-line biologic therapy for rheumatoid arthritis that does not respond to conventional disease-modifying drugs, Dr. Ai Lyn Tan reported at the annual meeting of the British Society for Rheumatology.

Rituximab is licensed in the United Kingdom for the treatment of adults with rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, conventional disease-modifying anti-rheumatic drugs (DMARDs) and to one or more tumor necrosis factor (TNF) inhibitors. In the United States it is licensed for use in combination with methotrexate for management of moderately to severely active RA that has not responded to treatment with one or more anti-TNF agents.

Licensure of the TNF inhibitors posed financial strains on the U.K. health care system, and the drugs were restricted in availability in some areas. Because of this lack of availability and the fact that rituximab had been shown to be effective in RA in trials of patients who had not previously received anti-TNF therapy, this drug has been used as a first-line biologic since 2004 by Dr. Tan and her colleagues at the University of Leeds (England) and Chapel Allerton Hospital, Leeds.

A total of 39 patients who had failed at least one DMARD have received two initial infusions of rituximab 2 weeks apart. In 17 patients the doses were 1,000 mg each, and in 22 the doses were 500 mg each.

Two-thirds of the patients were women. Their median age was 58 years and median disease duration was 7 years. Thirty of the patients were rheumatoid factor (RF) positive at baseline, and 16 were also antinuclear antibody (ANA) positive.

Clinical outcome data were available for 37 patients and safety data for all 39.

Clinical assessments using the Disease Activity Score (DAS)28 and EULAR response criteria were done at 3, 6, 9, and 12 months. The EULAR response criteria use the change in DAS and the level of DAS achieved to classify patients as good, moderate, or nonresponders.

At all time points, there was a significant improvement in DAS28. EULAR good responses were seen in 40% of patients at 3 months and in 50% of patients at 12 months, while overall EULAR responses were seen in 88% and 77%, respectively, at those time points.

By 6 months ANA became negative in 40% of patients in whom it had been positive at baseline, and in 88% of RF-positive patients the antibody level had fallen. Four of the previously RF-positive patients became seronegative by 6 months, and these reductions were sustained at 12 months, Dr. Tan wrote in a poster presented at the meeting.

Slightly better responses were seen in patients who received the higher dose, with 82% in the 500-mg group and 94% of those in the 1,000-mg group achieving EULAR responses. Nonetheless, she suggested that it might be “prudent” to start on lower doses since treatment is likely to be needed long term.

Thus far 25 patients have been retreated, at a median of 13 months after the initial infusions, and 7 have received a third treatment, at a median of 11 months after the second treatment.

Two patients were switched to anti-TNF therapy following early treatment failure and a third was switched following an allergic reaction to the second infusion of rituximab, according to Dr. Tan, who declared no conflicts of interest.

One 67-year-old patient with preexisting lung disease died 3 months after treatment from presumed bilateral bronchopneumonia and possible methotrexate pneumonitis, and a second 61-year-old man died of a myocardial infarction while awaiting coronary angiography for angina pectoris. This outcome was not considered to be related to therapy.

In an interview, Dr. Tan said that her study showed that rituximab is effective as first-line therapy in patients with severe RA. “This is important because it can be used in patients in whom the TNF blockers are contraindicated,” she said.

Almost half of the patients in this study had disease features that could have caused concerns with TNF blockade, such as risks of infection and strong ANA positivity (Rheumatology 2008:47;865-7).

“I think this will be an important role for rituximab in RA,” Dr. Tan said.

LIVERPOOL, ENGLAND — Rituximab has been used successfully in a real-world setting as a first-line biologic therapy for rheumatoid arthritis that does not respond to conventional disease-modifying drugs, Dr. Ai Lyn Tan reported at the annual meeting of the British Society for Rheumatology.

Rituximab is licensed in the United Kingdom for the treatment of adults with rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, conventional disease-modifying anti-rheumatic drugs (DMARDs) and to one or more tumor necrosis factor (TNF) inhibitors. In the United States it is licensed for use in combination with methotrexate for management of moderately to severely active RA that has not responded to treatment with one or more anti-TNF agents.

Licensure of the TNF inhibitors posed financial strains on the U.K. health care system, and the drugs were restricted in availability in some areas. Because of this lack of availability and the fact that rituximab had been shown to be effective in RA in trials of patients who had not previously received anti-TNF therapy, this drug has been used as a first-line biologic since 2004 by Dr. Tan and her colleagues at the University of Leeds (England) and Chapel Allerton Hospital, Leeds.

A total of 39 patients who had failed at least one DMARD have received two initial infusions of rituximab 2 weeks apart. In 17 patients the doses were 1,000 mg each, and in 22 the doses were 500 mg each.

Two-thirds of the patients were women. Their median age was 58 years and median disease duration was 7 years. Thirty of the patients were rheumatoid factor (RF) positive at baseline, and 16 were also antinuclear antibody (ANA) positive.

Clinical outcome data were available for 37 patients and safety data for all 39.

Clinical assessments using the Disease Activity Score (DAS)28 and EULAR response criteria were done at 3, 6, 9, and 12 months. The EULAR response criteria use the change in DAS and the level of DAS achieved to classify patients as good, moderate, or nonresponders.

At all time points, there was a significant improvement in DAS28. EULAR good responses were seen in 40% of patients at 3 months and in 50% of patients at 12 months, while overall EULAR responses were seen in 88% and 77%, respectively, at those time points.

By 6 months ANA became negative in 40% of patients in whom it had been positive at baseline, and in 88% of RF-positive patients the antibody level had fallen. Four of the previously RF-positive patients became seronegative by 6 months, and these reductions were sustained at 12 months, Dr. Tan wrote in a poster presented at the meeting.

Slightly better responses were seen in patients who received the higher dose, with 82% in the 500-mg group and 94% of those in the 1,000-mg group achieving EULAR responses. Nonetheless, she suggested that it might be “prudent” to start on lower doses since treatment is likely to be needed long term.

Thus far 25 patients have been retreated, at a median of 13 months after the initial infusions, and 7 have received a third treatment, at a median of 11 months after the second treatment.

Two patients were switched to anti-TNF therapy following early treatment failure and a third was switched following an allergic reaction to the second infusion of rituximab, according to Dr. Tan, who declared no conflicts of interest.

One 67-year-old patient with preexisting lung disease died 3 months after treatment from presumed bilateral bronchopneumonia and possible methotrexate pneumonitis, and a second 61-year-old man died of a myocardial infarction while awaiting coronary angiography for angina pectoris. This outcome was not considered to be related to therapy.

In an interview, Dr. Tan said that her study showed that rituximab is effective as first-line therapy in patients with severe RA. “This is important because it can be used in patients in whom the TNF blockers are contraindicated,” she said.

Almost half of the patients in this study had disease features that could have caused concerns with TNF blockade, such as risks of infection and strong ANA positivity (Rheumatology 2008:47;865-7).

“I think this will be an important role for rituximab in RA,” Dr. Tan said.

LIVERPOOL, ENGLAND — Rituximab has been used successfully in a real-world setting as a first-line biologic therapy for rheumatoid arthritis that does not respond to conventional disease-modifying drugs, Dr. Ai Lyn Tan reported at the annual meeting of the British Society for Rheumatology.

Rituximab is licensed in the United Kingdom for the treatment of adults with rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, conventional disease-modifying anti-rheumatic drugs (DMARDs) and to one or more tumor necrosis factor (TNF) inhibitors. In the United States it is licensed for use in combination with methotrexate for management of moderately to severely active RA that has not responded to treatment with one or more anti-TNF agents.

Licensure of the TNF inhibitors posed financial strains on the U.K. health care system, and the drugs were restricted in availability in some areas. Because of this lack of availability and the fact that rituximab had been shown to be effective in RA in trials of patients who had not previously received anti-TNF therapy, this drug has been used as a first-line biologic since 2004 by Dr. Tan and her colleagues at the University of Leeds (England) and Chapel Allerton Hospital, Leeds.

A total of 39 patients who had failed at least one DMARD have received two initial infusions of rituximab 2 weeks apart. In 17 patients the doses were 1,000 mg each, and in 22 the doses were 500 mg each.

Two-thirds of the patients were women. Their median age was 58 years and median disease duration was 7 years. Thirty of the patients were rheumatoid factor (RF) positive at baseline, and 16 were also antinuclear antibody (ANA) positive.

Clinical outcome data were available for 37 patients and safety data for all 39.

Clinical assessments using the Disease Activity Score (DAS)28 and EULAR response criteria were done at 3, 6, 9, and 12 months. The EULAR response criteria use the change in DAS and the level of DAS achieved to classify patients as good, moderate, or nonresponders.

At all time points, there was a significant improvement in DAS28. EULAR good responses were seen in 40% of patients at 3 months and in 50% of patients at 12 months, while overall EULAR responses were seen in 88% and 77%, respectively, at those time points.

By 6 months ANA became negative in 40% of patients in whom it had been positive at baseline, and in 88% of RF-positive patients the antibody level had fallen. Four of the previously RF-positive patients became seronegative by 6 months, and these reductions were sustained at 12 months, Dr. Tan wrote in a poster presented at the meeting.

Slightly better responses were seen in patients who received the higher dose, with 82% in the 500-mg group and 94% of those in the 1,000-mg group achieving EULAR responses. Nonetheless, she suggested that it might be “prudent” to start on lower doses since treatment is likely to be needed long term.

Thus far 25 patients have been retreated, at a median of 13 months after the initial infusions, and 7 have received a third treatment, at a median of 11 months after the second treatment.

Two patients were switched to anti-TNF therapy following early treatment failure and a third was switched following an allergic reaction to the second infusion of rituximab, according to Dr. Tan, who declared no conflicts of interest.

One 67-year-old patient with preexisting lung disease died 3 months after treatment from presumed bilateral bronchopneumonia and possible methotrexate pneumonitis, and a second 61-year-old man died of a myocardial infarction while awaiting coronary angiography for angina pectoris. This outcome was not considered to be related to therapy.

In an interview, Dr. Tan said that her study showed that rituximab is effective as first-line therapy in patients with severe RA. “This is important because it can be used in patients in whom the TNF blockers are contraindicated,” she said.

Almost half of the patients in this study had disease features that could have caused concerns with TNF blockade, such as risks of infection and strong ANA positivity (Rheumatology 2008:47;865-7).

“I think this will be an important role for rituximab in RA,” Dr. Tan said.