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The use of MTX in RA has limitations in certain patients, and many patients are unable to tolerate a high enough dose to achieve an optimal therapeutic benefit. Thus, for patients who do not tolerate MTX, monotherapy with adalimumab may be appropriate. DE011, a 26-week, randomized, double-blind, placebo-controlled, multicenter trial, evaluated the efficacy and safety of adalimumab monotherapy in 544 severely active RA patients for whom previous DMARD treatment had failed. Patients were randomized to placebo or monotherapywith 20 or 40 mg of adalimumab weekly or e.o.w. Time to clinical improvement with adalimumab was as early as 2 weeks. After 26 weeks, patients treated with adalimumab 20 or 40 mg weekly or e.o.w.

Table 3.2. Summary of primary and selected secondary endpoints from pivotal and other key trials of adalimumab in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, or Crohn's disease

Trial name Treatment" N Study Primary endpoint(s) Secondary endpoints duration

Table 3.2. Summary of primary and selected secondary endpoints from pivotal and other key trials of adalimumab in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, or Crohn's disease

Rheumatoid arthritis

ARMADA

Adalimumab (20, 40,

69, 67, 73

24 weeks

ACR20: 48%, 67%, 66% vs.

ACR50: 32 %, 55 %, 43 % vs.

(Weinblatt

80 mg) + MTX

15%

8%

et al. 2003)

Placebo + MTX

62

ACR70: 10%, 27%, 19% vs.

10%

AHAQ: -0.54, -0.62, -0.59

vs. -0.27

DE019 (Key

Adalimumab (40 mg

207, 212

52 weeks

AmTSS: 0.1, 0.8 vs. 2.7

ACR20: 59%, 55% vs. 24%

stone et al.

e.o.w., 20 mg weekly) +

ACR20 at Week 24: 63 %, 61 %

ACR50: 42%, 38% vs. 10%

2004a)

MTX

vs. 30%

ACR70: 23 %, 21 % vs. 5 %

Placebo + MTX

200

AHAQ: -0.59, -0.61 vs. -0.25

DE011 (van

Adalimumab (20 mg

106, 112,

26 weeks

ACR20: 36%, 39%, 46%, 53%

ACR50: 19%, 21 %, 22%,

de Putte et al.

e.o.w., 20 mg weekly,

113, 103

vs. 19%

35% vs. 8%

2004)

40 mg e.o.w., 40 mg

ACR70:9%, 10%, 12%, 18%

weekly)

vs. 2%

Placebo

110

Moderate EULAR response:

42 %, 48 %, 56 %, 63 % vs.

26%

Good EULAR response: 7%,

10%, 9%, 14% vs. 4%

HAQ: -0.29, -0.39, -0.38,

-0.49 vs. -0.07

STAR (Furst

Adalimumab +

318

24 weeks

AEs: no statistically significant

ACR20: 53% vs. 35%

et al. 2003)

DMARDs

differences between adalimu-

ACR50: 29% vs. 11%

Placebo + DMARDs

318

mab and placebo group in

ACR70: 15% vs. 4%

serious AEs; severe or life-

threatening AEs; AEs leading

to withdrawal; rates of infec-

tions or serious infections

Early rheumatoid arthritis

PREMIER

Adalimumab + MTX

268

2 years

ACR50 at 1 year: 62%, 41%, vs.

At year 2:

(Breedveld

Adalimumab

274

46%

ACR20: 69%, 49% vs. 56%

et al. 2005,

MTX

257

AmTSS at 1 year: 1.3, 3.0, vs.

ACR50: 59%, 37% vs. 43%

2006)

5.7

ACR70: 47%, 28% vs. 28%

ACR90: 27%, 9% vs. 13 %

AmTSS: 1.9, 5.5 vs. 10.4

DAS28 < 2.6: 49 %, 25 % vs.

25 %

ACR70 maintained

6 months: 49%, 25% vs. 27%

Psoriatic arthritis

ADEPT

Adalimumab

151

24 weeks

ACR20 at Week 12: 58% vs.

At Week 24:

(Mease et al.

Placebo

162

14%

ACR20: 57% vs. 15%

2005a, 2005b,

AmTSS at Week 24: -0.2 vs. 1.0

ACR50: 39% vs. 6%

2005c)

ACR70: 23 % vs. 1 %

PASI 50: 75% vs. 12%

PASI 75: 59% vs. 1%

PASI 90: 42 % vs. 0 %

PGA clear or almost clear:

71% vs. 12%

HAQ: -0.4 vs. -0.1

Table 3.2. (Cont.)

Trial name

Treatment"

N

Study duration

Primary endpoint(s)

Secondary endpoints

570 (Genove-

Adalimumab

51

12 weeks

ACR20: 39% vs. 16%

ACR50: 25 % vs. 2 %

se et al.

Placebo

49

ACR70: 14% vs. 0%

2005)

PGA clear or almost clear: 41 %

vs. 7%

ATL: -47% vs. -1.6%

AHAQ:-0.3 vs. -0.1

Ankylosing spondylitis

ATLAS (data

Adalimumab

208

12 weeks

ASAS20: 58% vs. 21 %

BASDAI 50: 45% vs. 16%

on file; van

Placebo

107

ASAS40: 41 % vs. 14%

der Heijde et

ASAS5/6: 49% vs. 13%

al. 2006)

Partial remission: 21 % vs. 4%

Psoriasis

528 (Langley

Adalimumab (40 mg

45, 50

12 weeks

PASI 75: 53 %, 80% vs. 4%

PASI 50: 76%, 88% vs. 17%

et al. 2005;

e.o.w., 40 mg weekly)

PASI 90: 24%, 48% vs. 0%

Wallace et al.

Placebo

52

PGA clear or almost clear: 49%,

2005b; 2005c;

76% vs. 2%

2005d)

DLQI of 0: 33 %, 42 % vs. 2 %

ASF-36 PCS: 3.9, 5.9 vs. 0.8

AEuroQOL-5D: 0.25, 0.22 vs. 0.04

529 (Langley

Adalimumab (40 mg

42, 44, 46

60 weeks

PASI 75: 67%, 73%, 50%

PASI 50: 76%, 75%, 78%

et al. 2005;

e.o.w., 40 mg weekly,

PASI 90: 36%, 55%, 41 %

Wallace et al.

placebo switched to

PGA clear or almost clear: 63 %,

2005b; 2005c;

40 mg e.o.w.)

79%, 66%

2005d)

DLQI of 0: 34%, 58%, 45%

SF-36 PCS: 3.4, 6.6, 2.9

AEuroQOL-5D: 0.21, 0.22, 0.17

Crohn's disease

CLASSIC-I

Adalimumab (160/

76, 75, 74

4 weeks

Clinical remission (CDAI

CDAI >70: 59%, 59%, 54% vs.

(Hanauer et

80 mg, 80/40 mg, 40/

<150) at Week 4: 36%,

37%

al. 2006)

20 mg)

24%, 18% vs. 12%

CDAI > 100: 50%, 40%, 34% vs.

Placebo

74

25 %

CLASSIC-II

Adalimumab

221 in OL

4-week

Clinical remission (CDAI

OL cohort: CDAI >70: 69%

(Sandborn et

cohort;

OL seg

<150) at Week 56: 43% in

CDAI 100: 61 %

al. 2005a)

55 in

ment

OL cohort

RCT arm

then 52-

week

RCTor

OL arm

a The dose of adalimumab is 40 mg e.o.w. unless specified otherwise

ACR American College of Rheumatology, ADEPT Adalimumab Effectiveness in Psoriatic Arthritis Trial, AE adverse event, ARMADA Anti-TNF Research Study Program of the Monoclonal Antibody Adalimumab in Rheumatoid Arthritis, ASAS ASes-sment in Ankylosing Spondylitis International Working Group Improvement Criteria, ATLAS Adalimumab Trial Evaluating Long-term Efficacy and Safety for Ankylosing Spondylitis, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, CDAI Crohn's Disease Activity Index, CLASSIC Clinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn's Disease, DAS Disease Activity Score, DLQI Dermatology Life Quality Index, DMARDs disease-modifying antirheumatic drugs, e.o.w. every other week, EULAR European League Against Rheumatism, HAQ Health Assessment Questionnaire, mTSS modified total Sharp score, MTX methotrexate, PASI Psoriasis Area and Severity Index, PGA Physician's Global Assessment, ReAct Research in Active Rheumatoid Arthritis Trial, SF-36 PCS Short Form-36 Physical Component Summary, STAR Safety Trial of Adalimumab in Rheumatoid Arthritis, TL target lesion had significantly better ACR response rates than those treated with placebo (see Table 3.2). Moderate European League Against Rheumatism (EULAR) response rates were also significantly greater with adalimumab than with placebo. The 40-mg weekly dose resulted in a slightly higher ACR response than 40 mg e.o.w. Adali-mumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function in patients with severe RA refractory to DMARD treatment (van de Putte et al. 2004).

The long-term efficacy and safety of adalimumab were evaluated in a rollover OLE study (DE018), enrolling 794 RA patients from DE011 and 3 other adalimumab trials in which the majority of patients received monotherapy. The clinical responses achieved at year 1 were sustained up to 5 years, with 67%, 40%, and 17% of patients maintaining ACR20, 50, and 70 responses, respectively. A total of 81 % of patients had a moderate EULAR response at 5 years, and initial reductions in tender and swollen joint counts were also maintained. High retention rates were achieved, suggesting high tolerability with adalimumab therapy (Burmester et al. 2003).

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Arthritis Joint Pain

Arthritis Joint Pain

Arthritis is a general term which is commonly associated with a number of painful conditions affecting the joints and bones. The term arthritis literally translates to joint inflammation.

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  • PRIMA
    What is monotherapy in rheumatoid arthritis?
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