Role of Biologics in Early RA
Content
بسم اللة الرحمه الرحيم وماأوتيتم مه العلم ءاال قليال
صدق اللة العظيم المؤمنون آية: 411
Role of Biologics In Treatment of Early Rheumatoid Arthritis
Rheumatoid arthritis (RA) affects
between 0.5% to 1% of the world's population. RA can cause chronic pain, dysfunction, and disability, particularly if it is not treated early.
MacGregor A, Silman AJ. Rheumatology. 3rd ed. Philadelphia: Elsevier Science, 2003.
The American College of Rheumatology Criteria for Rheumatoid Arthritis Classification. 1988
1. Prolonged morning stiffness at least 1 hour in 2. 3. 4. 5. 6. 7.
duration Arthritis in at least 3 joints Arthritis involving the hand joints Symmetrical arthritis The presence of rheumatoid nodules A positive test for rheumatoid factor, with significantly increased titers in the serum Radiographic changes typical of rheumatoid arthritis
Arnett FC, Edworthy SM, Bloch DA, et al. The American RheumatismAssociation 1987 revised criteria for the classification of rheumatoid arthritis.Arthritis Rheum. 1988;31:315-324.
New Rheumatoid Arthritis Criteria Released by ACR / EULAR Panel
Joint Involvement
Serology
Duration of synovitis
Acute phase reactants
1 medium-large joint (0
points)
Not positive for Less than 6 weeks (0 either RF or anti– CCP points) Neither CRP nor ESR is abnormal ( (0 points)
Neither CRP nor ESR is abnormal (0 points)
2-10 medium-large joints (1 point)
1-3 small joints (2
points)
One of these 2 tests are positive at low titer ( > the upper limit of normal but not higher than 3 times the upper limit of normal (2 points)
6 weeks or longer (1 point)
Abnormal CRP or abnormal ESR (1 point)
4-10 small joints (3
points)
At least 1test is positive at high titer (> 3 times the upper limit of normal (3 points)
Why Early Arthritis? Joint erosions occur in 67% of patients within 2 years of disease onset.
50% of RA patients are disabled
within 10 years of the onset of disease.
Active/ Severe disease is associated
with premature mortality from cardiac disease
Factors suggesting poor prognosis
1. Early age at onset.
2. Young female 3 . Swelling >20 joints 4 . Extra-articular disease 5.Radiological detection of erosions 6.Elevated ESR / CRP 7 .Elevated platelet count 8 . High titre rheumatoid factor
Criteria for remission
1)
Duration of morning stiffness not exceeding 15 minutes.
2) No fatigue. 3) 4) 5) 6)
No symptoms of joint pain. No joint tenderness or pain on motion. No soft tissue swelling in joints or tendon sheaths. ESR < 30 (female) and <20 (male)
NB Require 5 or more for at least 2 consecutive months. There must be no clinical manifestation of active vasculitis, pericarditis, pleuritis, or myositis or unexplained recent weight loss or fever attributable to rheumatoid arthritis.
Radiographic joint damage occurs early ``
and it is persistent and progressive, especially in the first 2 years of disease.
Fuchs HA, Kaye JJ, Callahan LF, Nance EP, Pincus T. Evidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease. J Rheumatol. 1989;16:585-591. Bukhari MA, Wiles NJ, Lunt M, et al. Influence of disease-modifying therapy on radiographic outcome in inflammatory polyarthritis at five years: results from a large observational inception study. Arthritis Rheum. 2003;48:46-53.
Early, aggressive, effective
treatment significantly reduces radiographic progression in RA.
Stenger AA, Van Leeuwen MA, Houtman PM, et al. Early effective suppression of inflammation in rheumatoid arthritis reduces radiographic progression. Br J Rheumatol. 1998;37:1157-1163.
If patients with very early RA were treated with disease-modifying antirheumatic drug (DMARD) earlier they will have better clinical outcomes than those treated later.
Nell VP, Machold KP, Eberl G, Stamm TA, Uffmann M, Smolen JS. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford). 2004.
van Aken J., Lard LR, le Cessie S., Hazes JM, Breedveld FC, Huizinga TW. Radiological outcome after four years of early versus delayed treatment strategy in patients with recent onset rheumatoid arthritis. Ann Rheum Dis. 2004;63:
Recent clinical trials have shown that
effective, aggressive therapy with traditional DMARDs may well control clinical symptoms but may not slow radiographic progression
The combination of an anti-tumor
necrosis factor-alpha (TNF-a) and MTX has been particularly effective.
MRI, Ultrasonography can use
for early detection of joint erosion in RA.
Ostergaard M, Peterfy C, Conaghan P, et al. OMERACT RheumatoidArthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. J Rheumatol. 2003;30:13851386
Structural Damage May Occur Before Visible Radiographically
MRI can demonstrate bone edema, a precursor to erosion, within 4 wk from onset of symptoms*
Distal aspect of the metacarpal on the right
* Wakefield RJ, et al. Br J Rheumatol. 1998;37(suppl):105. Images compliments of: O. Troum, MD, J. Crues, and Magna Vu.
DAS 28 SCORE
DAS 28 stands for "Disease Activity Score "
The following parameters are included in the calculation:
1. Number of joints tender to the touch (TEN) 2. Number of swollen joints (SW) 3. Erythrocyte sedimentation rate (ESR),(CRP) 4. Patient assessment of disease activity.
It is imperative to diagnose and effectively treat RA as early as possible.
BIOLOGIC AGENTS
T N F inhibitors: Adalimumab, Infliximab, Etanercept, Golimumab, certolizumab. IL1 inhibitor : Anakinra. Tcell Costimulation Blockade: Abatacept. B cell deplition: Rituximab. IL6 inhibitor: Tocilizumab. RANk-L blockade: Denosumab
` Treatment With Anti-TNF-α Agents in Early Rheumatoid Arthritis
Etanercept
(ERA) trial
The Etanercept in early Rheumatoid Arthritis (ERA) 1st group : MTX up to a maximum of 20 mg/wk)
2nd group : (BIW),
Etanercept monotherapy 10 mg SQ twice/wk
3nd group : Etanercept monotherapy 25 mg SQ) BIW. Both groups receiving etanercept responded much more rapidly than the group receiving MTX .
Bathon JM, Martin RW, Fleischmann RM, et al.Acomparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000; 1593. Genovese MC, Bathon JM, Martin RW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum. 2002;
RESULTS BY ONE YEAR
there was no statistically
significant difference in the ACR 20, ACR 50, and ACR 70. By that time, there was also no statistically significant difference in radiographic progression
BY 2 YEARS
There was a and clinical
significant difference only in the ACR 20 and radiographic progression was significantly less in the group treated with 25 mg BIW etanercept than in the MTX group
Patients(early rheumatoid)
treated in the ERA trial with etanercept 25 mg BIW were compared with patients with long-standing RA who were also treated with etanercept monotherapy at 25 mg BIW with mean disease duration of 12 years
In early rheumatoid group
(the HAQ score improved by 56%). In late rheumatoid group (the HAQ score improved by 39%).
This is considered as an
approval that the treatment of the disease early by the same biologic is more better than if it is treated late.
Infliximab
The Active-controlled Study of Patients receiving Infliximab for treatment of Rheumatoid arthritis of Early onset (ASPIRE)
To compare the efficacy of combination therapy with MTX and infliximab with MTX monotherapy in patients with early RA.
Clair EW, et al. Arthritis Rheum. 2004;50:3432-3443.
Patients with disease duration of 7 months were randomized into 3 groups: 1stgroup : MTX plus placebo. 2nd group : MTX plus 3 mg / kg infliximab 3rd group : MTX plus 6 mg / kg infliximab.
31%of the patients in the 6 mg/kg group
reached DAS remission versus 15% of the MTX monotherapy group
The ASPIRE study was the first to
conclusively show that an antiTNF-a combination with aggressively dosed MTX is superior to aggressively dosed MTX alone in early RA patients
This trial was also the first study conclusively showing that an aggressive dose of MTX combined with an effective dose of an anti-TNF-a significantly slows radiographic progression when compared with aggressively dosed MTX monotherapy in early RA.
Adalimumab
(PREMIER) STUDY
controlled study of 799 patients with active, early RA (mean duration 0.7 year)
This study compared
1-Aggressively dosed MTX monotherapy (1st group ). 2-Adalimumab monotherapy (2nd group). 3-Combination of aggressively dosed MTX and adalimumab (3rd group).
Breedveld FC, Kavanaugh A, Cohen SB. Early treatment of rheumatoid arthritis (RA) with adalimumab (Humira) plus methotrexate vs. adalimumab alone or methotrexate alone: The PREMIER
Study. Proceeding of the American College of Rheumatology, San Antonio, USA; 2004.
AFTER
ONE YEAR
1ST GROUP 2nd GROUP 54% 52A% 3rd GROUP 73% 62%
ACR20 ACR50
63% 46%
ACR70
28%
26%
42%
1ST 2ndg 3rd GROUP GROUP GROUP
DAS 21% SCORE
23%
43%
1ST GROUP
RADIOGR PHIC PRGRESSI ON
2nd GROUP
3rd GROUP
10.4
5.5
1.9
This study demonstrated that effectiveness of MTX combined with an anti-TNF-α versus either mono-therapy with respect to clinical, functional, and radiographic outcomes.
There's clearly substantial radiographic progression with methotrexate monotherapy vs either of the infliximab or the adalimumab when given in combination with methotrexate.
This strategy of adding a TNF inhibitor here is superior in terms of inhibiting radiographic progression to methotrexate monotherapy
Golimumab
Golimumab is a human
monoclonal antibody to TNF-alpha that is under development at a dose of 100 mg administered subcutaneously every 4 weeks..
16-week results had been
presented evaluating golimumab in patients with active RA despite methotrexate and had demonstrated statistical superiority for all doses (50-100 mg every 2-4 weeks) compared with placebo.
Zhou H, Xu Z, Rahman MU, et al. Exposure-efficacy assessment of golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: application of population pharmacokinetic/pharmacodynamic modeling. Program and abstracts of the American College of Rheumatology 70th Annual Meeting; November 11-15, 2006; Washington, DC. Presentation 966.
Certolizumab
RAPID 1
involved 982 patients,
1393 randomized to certolizumab 200 mg plus methotrexate, 2390 to certolizumab 400 mg plus methotrexate, 3199 to placebo plus methotrexate.
Patients in the certolizumab arms
reported significantly improved health-related quality of life compared with the placebo group, beginning at week 12 and continuing through week 52 of the study.
Anakinra
In a monotherapy trial of
anakinra in 472 patients with active RA, patients received either placebo or anakinra at doses of 30, 75, or 150 mg/day for 24 weeks
Baumgartner SW, Fleischmann RM, Moreland LW, Schiff MH, Markenson J, Whitmore JB. Etanercept (Enbrel) in patients with rheumatoid arthritis with recent onset versus established disease: improvement in disability. J Rheumatol. 2004;31:1532-1537.
RESULTS AFTER 24Ws
ANAKINRA (30mg)
ACR20 30%
ANAKINRA (75mg)
34%
ANAKINRA (150mg)
43%
PLACEBO
27%
Abatacept
Abatacept inhibits
progression of structural damage in rheumatoid arthritis: results from the long-term extension of the AIM trial.
Kremer etal.ACR,2005
Rituximab
This was a trial that was done with over 500 patients with rituximab. The patients had had an inadequate response to methotrexate,
Here we have ACR20 responses in the 57%
in the 1000 mg group and 59% in the 500 mg group. So really no difference in terms of the milligram dosage effects at ACR20, 50, or 70 levels. Then the remission was achieved in 9% at week 48 in the 1000 mg group and 11% with the 500 mg arm. It looks like both doses of rituximab can work very well in a methotrexate inadequate response population.
Tocilizumab
A trial of 164 patients with RA patients
were randomized to receive either: 1- tocilizumab (4 mg/kg body weight)1stgr 2-(8 mg/kg body weight)2nd gr 3-(placebo)3rd gr Tocilizumab was administered IV every 4 weeks for a total of 3 months.
Nishimoto N, Yoshizaki K, Miyasaka N, et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor
antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2004;50:1761-1769
.
At 3 months
1st gr 2ndgr 3rdgr
ACR20
57% (4mg)
78% (8mg)
11% (placebo)
Receptor Activator for Nuclear Factor κ B Ligand
Conclusion
The initial challenge in treating RA is 1-Early identifying patients
2-Early treating them.
Current evidence strongly suggests that:
The combination of MTX and a TNF-α inhibitor May be the most effective combination that it is significantly improve the clinical, radiographic, and functional outcomes of patients with early RA.
Thank you
Thank you
صدق اللة العظيم المؤمنون آية: 411
Role of Biologics In Treatment of Early Rheumatoid Arthritis
Rheumatoid arthritis (RA) affects
between 0.5% to 1% of the world's population. RA can cause chronic pain, dysfunction, and disability, particularly if it is not treated early.
MacGregor A, Silman AJ. Rheumatology. 3rd ed. Philadelphia: Elsevier Science, 2003.
The American College of Rheumatology Criteria for Rheumatoid Arthritis Classification. 1988
1. Prolonged morning stiffness at least 1 hour in 2. 3. 4. 5. 6. 7.
duration Arthritis in at least 3 joints Arthritis involving the hand joints Symmetrical arthritis The presence of rheumatoid nodules A positive test for rheumatoid factor, with significantly increased titers in the serum Radiographic changes typical of rheumatoid arthritis
Arnett FC, Edworthy SM, Bloch DA, et al. The American RheumatismAssociation 1987 revised criteria for the classification of rheumatoid arthritis.Arthritis Rheum. 1988;31:315-324.
New Rheumatoid Arthritis Criteria Released by ACR / EULAR Panel
Joint Involvement
Serology
Duration of synovitis
Acute phase reactants
1 medium-large joint (0
points)
Not positive for Less than 6 weeks (0 either RF or anti– CCP points) Neither CRP nor ESR is abnormal ( (0 points)
Neither CRP nor ESR is abnormal (0 points)
2-10 medium-large joints (1 point)
1-3 small joints (2
points)
One of these 2 tests are positive at low titer ( > the upper limit of normal but not higher than 3 times the upper limit of normal (2 points)
6 weeks or longer (1 point)
Abnormal CRP or abnormal ESR (1 point)
4-10 small joints (3
points)
At least 1test is positive at high titer (> 3 times the upper limit of normal (3 points)
Why Early Arthritis? Joint erosions occur in 67% of patients within 2 years of disease onset.
50% of RA patients are disabled
within 10 years of the onset of disease.
Active/ Severe disease is associated
with premature mortality from cardiac disease
Factors suggesting poor prognosis
1. Early age at onset.
2. Young female 3 . Swelling >20 joints 4 . Extra-articular disease 5.Radiological detection of erosions 6.Elevated ESR / CRP 7 .Elevated platelet count 8 . High titre rheumatoid factor
Criteria for remission
1)
Duration of morning stiffness not exceeding 15 minutes.
2) No fatigue. 3) 4) 5) 6)
No symptoms of joint pain. No joint tenderness or pain on motion. No soft tissue swelling in joints or tendon sheaths. ESR < 30 (female) and <20 (male)
NB Require 5 or more for at least 2 consecutive months. There must be no clinical manifestation of active vasculitis, pericarditis, pleuritis, or myositis or unexplained recent weight loss or fever attributable to rheumatoid arthritis.
Radiographic joint damage occurs early ``
and it is persistent and progressive, especially in the first 2 years of disease.
Fuchs HA, Kaye JJ, Callahan LF, Nance EP, Pincus T. Evidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease. J Rheumatol. 1989;16:585-591. Bukhari MA, Wiles NJ, Lunt M, et al. Influence of disease-modifying therapy on radiographic outcome in inflammatory polyarthritis at five years: results from a large observational inception study. Arthritis Rheum. 2003;48:46-53.
Early, aggressive, effective
treatment significantly reduces radiographic progression in RA.
Stenger AA, Van Leeuwen MA, Houtman PM, et al. Early effective suppression of inflammation in rheumatoid arthritis reduces radiographic progression. Br J Rheumatol. 1998;37:1157-1163.
If patients with very early RA were treated with disease-modifying antirheumatic drug (DMARD) earlier they will have better clinical outcomes than those treated later.
Nell VP, Machold KP, Eberl G, Stamm TA, Uffmann M, Smolen JS. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford). 2004.
van Aken J., Lard LR, le Cessie S., Hazes JM, Breedveld FC, Huizinga TW. Radiological outcome after four years of early versus delayed treatment strategy in patients with recent onset rheumatoid arthritis. Ann Rheum Dis. 2004;63:
Recent clinical trials have shown that
effective, aggressive therapy with traditional DMARDs may well control clinical symptoms but may not slow radiographic progression
The combination of an anti-tumor
necrosis factor-alpha (TNF-a) and MTX has been particularly effective.
MRI, Ultrasonography can use
for early detection of joint erosion in RA.
Ostergaard M, Peterfy C, Conaghan P, et al. OMERACT RheumatoidArthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. J Rheumatol. 2003;30:13851386
Structural Damage May Occur Before Visible Radiographically
MRI can demonstrate bone edema, a precursor to erosion, within 4 wk from onset of symptoms*
Distal aspect of the metacarpal on the right
* Wakefield RJ, et al. Br J Rheumatol. 1998;37(suppl):105. Images compliments of: O. Troum, MD, J. Crues, and Magna Vu.
DAS 28 SCORE
DAS 28 stands for "Disease Activity Score "
The following parameters are included in the calculation:
1. Number of joints tender to the touch (TEN) 2. Number of swollen joints (SW) 3. Erythrocyte sedimentation rate (ESR),(CRP) 4. Patient assessment of disease activity.
It is imperative to diagnose and effectively treat RA as early as possible.
BIOLOGIC AGENTS
T N F inhibitors: Adalimumab, Infliximab, Etanercept, Golimumab, certolizumab. IL1 inhibitor : Anakinra. Tcell Costimulation Blockade: Abatacept. B cell deplition: Rituximab. IL6 inhibitor: Tocilizumab. RANk-L blockade: Denosumab
` Treatment With Anti-TNF-α Agents in Early Rheumatoid Arthritis
Etanercept
(ERA) trial
The Etanercept in early Rheumatoid Arthritis (ERA) 1st group : MTX up to a maximum of 20 mg/wk)
2nd group : (BIW),
Etanercept monotherapy 10 mg SQ twice/wk
3nd group : Etanercept monotherapy 25 mg SQ) BIW. Both groups receiving etanercept responded much more rapidly than the group receiving MTX .
Bathon JM, Martin RW, Fleischmann RM, et al.Acomparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000; 1593. Genovese MC, Bathon JM, Martin RW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum. 2002;
RESULTS BY ONE YEAR
there was no statistically
significant difference in the ACR 20, ACR 50, and ACR 70. By that time, there was also no statistically significant difference in radiographic progression
BY 2 YEARS
There was a and clinical
significant difference only in the ACR 20 and radiographic progression was significantly less in the group treated with 25 mg BIW etanercept than in the MTX group
Patients(early rheumatoid)
treated in the ERA trial with etanercept 25 mg BIW were compared with patients with long-standing RA who were also treated with etanercept monotherapy at 25 mg BIW with mean disease duration of 12 years
In early rheumatoid group
(the HAQ score improved by 56%). In late rheumatoid group (the HAQ score improved by 39%).
This is considered as an
approval that the treatment of the disease early by the same biologic is more better than if it is treated late.
Infliximab
The Active-controlled Study of Patients receiving Infliximab for treatment of Rheumatoid arthritis of Early onset (ASPIRE)
To compare the efficacy of combination therapy with MTX and infliximab with MTX monotherapy in patients with early RA.
Clair EW, et al. Arthritis Rheum. 2004;50:3432-3443.
Patients with disease duration of 7 months were randomized into 3 groups: 1stgroup : MTX plus placebo. 2nd group : MTX plus 3 mg / kg infliximab 3rd group : MTX plus 6 mg / kg infliximab.
31%of the patients in the 6 mg/kg group
reached DAS remission versus 15% of the MTX monotherapy group
The ASPIRE study was the first to
conclusively show that an antiTNF-a combination with aggressively dosed MTX is superior to aggressively dosed MTX alone in early RA patients
This trial was also the first study conclusively showing that an aggressive dose of MTX combined with an effective dose of an anti-TNF-a significantly slows radiographic progression when compared with aggressively dosed MTX monotherapy in early RA.
Adalimumab
(PREMIER) STUDY
controlled study of 799 patients with active, early RA (mean duration 0.7 year)
This study compared
1-Aggressively dosed MTX monotherapy (1st group ). 2-Adalimumab monotherapy (2nd group). 3-Combination of aggressively dosed MTX and adalimumab (3rd group).
Breedveld FC, Kavanaugh A, Cohen SB. Early treatment of rheumatoid arthritis (RA) with adalimumab (Humira) plus methotrexate vs. adalimumab alone or methotrexate alone: The PREMIER
Study. Proceeding of the American College of Rheumatology, San Antonio, USA; 2004.
AFTER
ONE YEAR
1ST GROUP 2nd GROUP 54% 52A% 3rd GROUP 73% 62%
ACR20 ACR50
63% 46%
ACR70
28%
26%
42%
1ST 2ndg 3rd GROUP GROUP GROUP
DAS 21% SCORE
23%
43%
1ST GROUP
RADIOGR PHIC PRGRESSI ON
2nd GROUP
3rd GROUP
10.4
5.5
1.9
This study demonstrated that effectiveness of MTX combined with an anti-TNF-α versus either mono-therapy with respect to clinical, functional, and radiographic outcomes.
There's clearly substantial radiographic progression with methotrexate monotherapy vs either of the infliximab or the adalimumab when given in combination with methotrexate.
This strategy of adding a TNF inhibitor here is superior in terms of inhibiting radiographic progression to methotrexate monotherapy
Golimumab
Golimumab is a human
monoclonal antibody to TNF-alpha that is under development at a dose of 100 mg administered subcutaneously every 4 weeks..
16-week results had been
presented evaluating golimumab in patients with active RA despite methotrexate and had demonstrated statistical superiority for all doses (50-100 mg every 2-4 weeks) compared with placebo.
Zhou H, Xu Z, Rahman MU, et al. Exposure-efficacy assessment of golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: application of population pharmacokinetic/pharmacodynamic modeling. Program and abstracts of the American College of Rheumatology 70th Annual Meeting; November 11-15, 2006; Washington, DC. Presentation 966.
Certolizumab
RAPID 1
involved 982 patients,
1393 randomized to certolizumab 200 mg plus methotrexate, 2390 to certolizumab 400 mg plus methotrexate, 3199 to placebo plus methotrexate.
Patients in the certolizumab arms
reported significantly improved health-related quality of life compared with the placebo group, beginning at week 12 and continuing through week 52 of the study.
Anakinra
In a monotherapy trial of
anakinra in 472 patients with active RA, patients received either placebo or anakinra at doses of 30, 75, or 150 mg/day for 24 weeks
Baumgartner SW, Fleischmann RM, Moreland LW, Schiff MH, Markenson J, Whitmore JB. Etanercept (Enbrel) in patients with rheumatoid arthritis with recent onset versus established disease: improvement in disability. J Rheumatol. 2004;31:1532-1537.
RESULTS AFTER 24Ws
ANAKINRA (30mg)
ACR20 30%
ANAKINRA (75mg)
34%
ANAKINRA (150mg)
43%
PLACEBO
27%
Abatacept
Abatacept inhibits
progression of structural damage in rheumatoid arthritis: results from the long-term extension of the AIM trial.
Kremer etal.ACR,2005
Rituximab
This was a trial that was done with over 500 patients with rituximab. The patients had had an inadequate response to methotrexate,
Here we have ACR20 responses in the 57%
in the 1000 mg group and 59% in the 500 mg group. So really no difference in terms of the milligram dosage effects at ACR20, 50, or 70 levels. Then the remission was achieved in 9% at week 48 in the 1000 mg group and 11% with the 500 mg arm. It looks like both doses of rituximab can work very well in a methotrexate inadequate response population.
Tocilizumab
A trial of 164 patients with RA patients
were randomized to receive either: 1- tocilizumab (4 mg/kg body weight)1stgr 2-(8 mg/kg body weight)2nd gr 3-(placebo)3rd gr Tocilizumab was administered IV every 4 weeks for a total of 3 months.
Nishimoto N, Yoshizaki K, Miyasaka N, et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor
antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2004;50:1761-1769
.
At 3 months
1st gr 2ndgr 3rdgr
ACR20
57% (4mg)
78% (8mg)
11% (placebo)
Receptor Activator for Nuclear Factor κ B Ligand
Conclusion
The initial challenge in treating RA is 1-Early identifying patients
2-Early treating them.
Current evidence strongly suggests that:
The combination of MTX and a TNF-α inhibitor May be the most effective combination that it is significantly improve the clinical, radiographic, and functional outcomes of patients with early RA.
Thank you
Thank you
