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Rituxan + Mtx Curbs Joint Damage

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  1. #1
    Donna G Guest

    Default Rituxan + Mtx Curbs Joint Damage





    Reviewed*by*Zalman S. Agus, MD; Emeritus Professor, Perelman School
    of Medicine at the University of Pennsylvania

    Progression of joint damage in early RA is linked to disease activity.
    This link is dissociated upon treatment with TNF- or IL-6-inhibitors
    plus methotrexate.

    This study shows that rituximab, which targets B-cells, plus
    methotrexate also retards joint damage independently of its effects on
    disease activity.

    Adding the B-cell depleting agent rituximab (Rituxan) to methotrexate
    slowed joint damage progression in patients with rheumatoid arthritis
    (RA) regardless of the level of disease activity, Austrian researchers
    reported.

    At 1 year, patients with low disease activity receiving rituximab in
    combination with methotrexate had a change in joint damage scores of
    0.38, according to Daniel Aletaha, MD, and colleagues from the Medical
    University of Vienna.

    Similar changes were seen among those with moderate and high disease
    activity (0.39 and ?0.05, respectively, P=0.5 for all), the researchers
    reported in the January Annals of the Rheumatic Diseases.

    In contrast, patients receiving methotrexate
    alone had more pronounced changes in joint damage scores, at a mean of
    0.40 with low disease activity, 1.04 for moderate activity, and 1.31 for
    high activity, differences that approached statistical significance
    (P=0.058).

    The natural history of rheumatoid arthritis involves the gradual accrual
    of irreversible joint destruction, which can occur within a year or two
    of disease onset.

    In addition, in patients receiving suboptimal therapy, joint damage
    closely tracks disease activity and is primarily driven by joint
    swelling and acute phase reactants such as C-reactive protein (CRP).


    ====MORE CLINICAL STUDY


    Previous research has demonstrated that cytokine-directed biologic
    therapy, particularly using agents targeting tumor necrosis factor (TNF)
    and interleukin-6, can uncouple this destructive parallel process.

    "Both TNF and IL-6 blockers inhibit proinflammatory cytokines which are
    believed to play a major role in the pathways leading to osteoclast and
    chondrocyte activation, the pivotal populations responsible for bony and
    cartilage damage," Aletaha and colleagues wrote.

    However, whether cell-depleting therapies could have similar effects has
    not been explored, so the researchers conducted a retrospective analysis
    of data from the IMAGE trial, which was a phase III trial comparing
    rituximab plus methotrexate with methotrexate alone in patients with RA
    who had not previously received either agent.

    The current analysis included 188 patients on methotrexate monotherapy
    and 204 receiving methotrexate plus rituximab.

    After a year of treatment, significant differences were seen between the
    methotrexate monotherapy and combination groups on multiple endpoints,
    including tender joint counts, patient and physician global assessments,
    pain, CRP, erythrocyte sedimentation rate, disease activity scores in 28
    joints, and health assessment questionnaire (P<0.001 for all).

    When the researchers analyzed patients' x-ray changes in relation to
    disease activity, they found little difference between the two treatment
    groups for patients with low disease activity, with scores differing by
    only 0.02 points.

    However, for the moderate and high disease
    groups, there were "remarkable differences" of 0.65 (P=0.003) and 1.36
    (P=0.05), respectively, they reported.

    A change in score greater than 0.25 was considered "unequivocal
    progression," they noted.

    They also looked at the two components of the overall joint damage
    scores, and found that for erosions, changes in the methotrexate
    monotherapy group at 1 year ranged from 0.37 in the low disease group to
    0.85 in the high disease group, while the corresponding numbers in the
    rituximab group were 0.26 and ?0.02.

    For joint space narrowing, scores in the methotrexate group were 0.03 in
    the low disease group and 0.46 in the high disease group, while scores
    in the rituximab group were 0.12 and ?0.02 in the low and high disease
    activity groups, respectively.

    Because swollen joints and CRP correlate well with disease damage, the
    researchers also looked at radiographic outcomes according to these
    endpoints.

    They found that with rituximab treatment, even patients in the highest
    tertile of swollen joints had only minimal progression in joint damage
    at 1 year compared with those in the lowest tertile (0.31 versus 0.28,
    P=0.97).

    In contrast, patients receiving methotrexate alone in the highest
    tertile of swollen joints had significantly more x-ray changes compared
    with those in the lowest tertile (1.33 versus 0.32, P=0.009). Similar
    results were seen when patients were classified according to levels of
    CRP at 1 year, with the greatest differences again being seen for the
    highest level of CRP.

    These results suggest that B-cell depletion with rituximab can have
    effects on decoupling disease activity from damage similar to the
    benefits reported for the TNF inhibitors and other cytokine-targeting
    treatments.

    "Aletaha and colleagues have demonstrated a similar dissociation between
    clinical and structural outcomes in patients treated with rituximab,
    suggesting that the mechanisms explaining this dissociation are not
    unique to anti-TNF drugs," observed Edith Villeneuve, MD, and Boulos
    Haraoui, MD, of the University of Montreal, in an accompanying
    editorial.

    Among the possible mechanisms for the effects of B-cell depletion in
    preventing damage are reductions in autoantibodies and immune complexes
    that in turn can limit the production of inflammatory cytokines, the
    researchers explained.

    Limitations of this analysis included its exploratory and retrospective
    design and the inclusion of only patients who had not previously
    received methotrexate.

    The lead author and one co-author advise and speak for Roche, and the
    co-author also receives grants and research support from the company.

    ..
    ..
    Donna G.
    ..

    1) Rejoice always, Pray continually, Give thanks in all circumstances,
    For this is God's will for you in Christ Jesus. ( I Thessalonians
    5:16-18 NIV )

    2) It is not the mountain we conquer but ourselves.
    - Edmund Hillary

    3) ANGELS EXIST, but some times, since they don't all have wings, we
    call them FRIENDS......


  2. #2
    Harvey Guest

    Default Re: Rituxan + Mtx Curbs Joint Damage

    Thank you Donna..... Harv



    "Donna G" wrote in message
    news:[email protected]..





    Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School
    of Medicine at the University of Pennsylvania

    Progression of joint damage in early RA is linked to disease activity.
    This link is dissociated upon treatment with TNF- or IL-6-inhibitors
    plus methotrexate.

    This study shows that rituximab, which targets B-cells, plus
    methotrexate also retards joint damage independently of its effects on
    disease activity.

    Adding the B-cell depleting agent rituximab (Rituxan) to methotrexate
    slowed joint damage progression in patients with rheumatoid arthritis
    (RA) regardless of the level of disease activity, Austrian researchers
    reported.

    At 1 year, patients with low disease activity receiving rituximab in
    combination with methotrexate had a change in joint damage scores of
    0.38, according to Daniel Aletaha, MD, and colleagues from the Medical
    University of Vienna.

    Similar changes were seen among those with moderate and high disease
    activity (0.39 and ?0.05, respectively, P=0.5 for all), the researchers
    reported in the January Annals of the Rheumatic Diseases.

    In contrast, patients receiving methotrexate
    alone had more pronounced changes in joint damage scores, at a mean of
    0.40 with low disease activity, 1.04 for moderate activity, and 1.31 for
    high activity, differences that approached statistical significance
    (P=0.058).

    The natural history of rheumatoid arthritis involves the gradual accrual
    of irreversible joint destruction, which can occur within a year or two
    of disease onset.

    In addition, in patients receiving suboptimal therapy, joint damage
    closely tracks disease activity and is primarily driven by joint
    swelling and acute phase reactants such as C-reactive protein (CRP).


    ====MORE CLINICAL STUDY


    Previous research has demonstrated that cytokine-directed biologic
    therapy, particularly using agents targeting tumor necrosis factor (TNF)
    and interleukin-6, can uncouple this destructive parallel process.

    "Both TNF and IL-6 blockers inhibit proinflammatory cytokines which are
    believed to play a major role in the pathways leading to osteoclast and
    chondrocyte activation, the pivotal populations responsible for bony and
    cartilage damage," Aletaha and colleagues wrote.

    However, whether cell-depleting therapies could have similar effects has
    not been explored, so the researchers conducted a retrospective analysis
    of data from the IMAGE trial, which was a phase III trial comparing
    rituximab plus methotrexate with methotrexate alone in patients with RA
    who had not previously received either agent.

    The current analysis included 188 patients on methotrexate monotherapy
    and 204 receiving methotrexate plus rituximab.

    After a year of treatment, significant differences were seen between the
    methotrexate monotherapy and combination groups on multiple endpoints,
    including tender joint counts, patient and physician global assessments,
    pain, CRP, erythrocyte sedimentation rate, disease activity scores in 28
    joints, and health assessment questionnaire (P<0.001 for all).

    When the researchers analyzed patients' x-ray changes in relation to
    disease activity, they found little difference between the two treatment
    groups for patients with low disease activity, with scores differing by
    only 0.02 points.

    However, for the moderate and high disease
    groups, there were "remarkable differences" of 0.65 (P=0.003) and 1.36
    (P=0.05), respectively, they reported.

    A change in score greater than 0.25 was considered "unequivocal
    progression," they noted.

    They also looked at the two components of the overall joint damage
    scores, and found that for erosions, changes in the methotrexate
    monotherapy group at 1 year ranged from 0.37 in the low disease group to
    0.85 in the high disease group, while the corresponding numbers in the
    rituximab group were 0.26 and ?0.02.

    For joint space narrowing, scores in the methotrexate group were 0.03 in
    the low disease group and 0.46 in the high disease group, while scores
    in the rituximab group were 0.12 and ?0.02 in the low and high disease
    activity groups, respectively.

    Because swollen joints and CRP correlate well with disease damage, the
    researchers also looked at radiographic outcomes according to these
    endpoints.

    They found that with rituximab treatment, even patients in the highest
    tertile of swollen joints had only minimal progression in joint damage
    at 1 year compared with those in the lowest tertile (0.31 versus 0.28,
    P=0.97).

    In contrast, patients receiving methotrexate alone in the highest
    tertile of swollen joints had significantly more x-ray changes compared
    with those in the lowest tertile (1.33 versus 0.32, P=0.009). Similar
    results were seen when patients were classified according to levels of
    CRP at 1 year, with the greatest differences again being seen for the
    highest level of CRP.

    These results suggest that B-cell depletion with rituximab can have
    effects on decoupling disease activity from damage similar to the
    benefits reported for the TNF inhibitors and other cytokine-targeting
    treatments.

    "Aletaha and colleagues have demonstrated a similar dissociation between
    clinical and structural outcomes in patients treated with rituximab,
    suggesting that the mechanisms explaining this dissociation are not
    unique to anti-TNF drugs," observed Edith Villeneuve, MD, and Boulos
    Haraoui, MD, of the University of Montreal, in an accompanying
    editorial.

    Among the possible mechanisms for the effects of B-cell depletion in
    preventing damage are reductions in autoantibodies and immune complexes
    that in turn can limit the production of inflammatory cytokines, the
    researchers explained.

    Limitations of this analysis included its exploratory and retrospective
    design and the inclusion of only patients who had not previously
    received methotrexate.

    The lead author and one co-author advise and speak for Roche, and the
    co-author also receives grants and research support from the company.

    ..
    ..
    Donna G.
    ..

    1) Rejoice always, Pray continually, Give thanks in all circumstances,
    For this is God's will for you in Christ Jesus. ( I Thessalonians
    5:16-18 NIV )

    2) It is not the mountain we conquer but ourselves.
    - Edmund Hillary

    3) ANGELS EXIST, but some times, since they don't all have wings, we
    call them FRIENDS......


  3. #3
    Donna G Guest

    Default Re: Rituxan + Mtx Curbs Joint Damage




    Hey, any time, Harv! I was happy to see this, as this is one of the
    combos I am on and the rituxan really does the trick for me.

    ..
    ..
    Donna G.
    ..

    1) Rejoice always, Pray continually, Give thanks in all circumstances,
    For this is God's will for you in Christ Jesus. ( I Thessalonians
    5:16-18 NIV )

    2) It is not the mountain we conquer but ourselves.
    - Edmund Hillary

    3) ANGELS EXIST, but some times, since they don't all have wings, we
    call them FRIENDS......


  4. #4
    Diane Guest

    Default Re: Rituxan + Mtx Curbs Joint Damage

    Thank you Donna and I'm so glad to hear that this also helps you! :-)

    Hugs,

    Diane

    "Donna G" <[email protected]> wrote in message
    news:[email protected]..
    >
    >
    >
    > Hey, any time, Harv! I was happy to see this, as this is one of the
    > combos I am on and the rituxan really does the trick for me.
    >
    > .
    > .
    > Donna G.
    > .
    >
    > 1) Rejoice always, Pray continually, Give thanks in all circumstances,
    > For this is God's will for you in Christ Jesus. ( I Thessalonians
    > 5:16-18 NIV )
    >
    > 2) It is not the mountain we conquer but ourselves.
    > - Edmund Hillary
    >
    > 3) ANGELS EXIST, but some times, since they don't all have wings, we
    > call them FRIENDS......
    >


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