Golimumab, A Human Anti-TNF Monoclonal Antibody, Administered Subcutaneously Every Four Weeks As Monotherapy in Patients with Active Rheumatoid Arthritis Despite Disease Modifying Antirheumatic Drug Therapy: Week 104 Results of Clinical, Radiographic and Safety Assessments

Tsutomu Takeuchi¹, Masayoshi Harigai², Yoshiya Tanaka³, Hisashi Yamanaka⁴, Naoki Ishiguro⁵, Kazuhiko Yamamoto⁶, Minoru Kanazawa⁷, Yoshinori Murakami⁸, Toru Yoshinari⁹, Daniel Baker¹⁰, Nobuyuki Miyasaka¹¹ and Takao Koike¹², ¹Keio University School of Medicine, Tokyo, Japan, ²Dept of Pharmacovigilance, Tokyo Medical and Dental University, Tokyo, Japan, ³The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan, ⁴Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, ⁵Department of Orthopedic Surgery, Nagoya University, Graduate School & Faculty of Medicine, Nagoya, Aichi, Japan, ⁶Department of Allergy & Rheumatology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan, ⁷Director of Respiratory Center Professor of Respiratory, Medicine Saitama Medical University, Moroyama, Iruma-Gun, Saimata, Japan, ⁸Medical writing, Janssen Pharmaceutical KK, Tokyo, Japan, ⁹2-6-18, Kitahama, Chuo-ku, Mitsubishi Tanabe Pharma Corporation, Osaka, Japan, ¹⁰Janssen Research & Development, LLC., Spring House, PA, ¹¹Department of Medicine and Rheumatology and Global Center of Excellence Program, Tokyo Medical and Dental University, Tokyo, Japan, ¹²Sapporo medical center NTT EC, Sapporo, Japan

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Japanese and rheumatoid arthritis (RA)

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy

Session Type: Abstract Submissions (ACR)

Golimumab, A Human Anti-TNF Monoclonal Antibody, Administered Subcutaneously Every Four Weeks as Monotherapy in Patients with Active Rheumatoid Arthritis Despite Disease Modifying Antirheumatic Drug Therapy: Week 104 Results of Clinical, Radiographic and Safety Assessments

Background/Purpose: To assess the long-term efficacy and safety of golimumab (GLM) as monotherapy in Japanese patients (pts) with active rheumatoid arthritis (RA) despite DMARD therapy.

Methods: GO-MONO is a multicenter, randomized, double-blind, placebo (PBO)-controlled study in pts with active RA despite treatment with DMARDs. Pts were randomized to SC PBO, GLM50 mg, or GLM100 mg q4wks as monotherapy. At wk16, pts in the PBO group (grp) crossed over (CO) GLM50 mg q4wks. Treatment with GLM continued to wk120. Primary endpoint was the proportion of pts achieving ACR20 at wk14. Secondary endpoints included ACR50, ACR70, and ACR-N, DAS28 and HAQ and changes from BL to wks 24/52/104/120 in total modified vdH-Sharp (vdH-S) score. Data were analyzed using all patients receiving ≥1 dose of study treatment. Missing clinical response data were not imputed. For vdH-S score, treatment grp comparisons at wks 52/104 were based on initial randomized grps. Missing data were imputed using median change from BL in total vdH-S scores (TSS) of all pts or by linear extrapolation. Wk52 data have been reported; wk104 results of efficacy are now reported. Safety data from all treatment period are reported as incidence per 100-patient-years.

Results: Long-term efficacy and safety data are shown in the Table. Clinical remission was defined as DAS28(ESR) < 2.6 and HAQ remission was defined as HAQ < 0.5 maintained between wk52 and wk104. Median changes from baseline to wk52 were 1.0 in PBO and GLM 50mg, and 0 in GLM100 mg. Median changes from baseline to wk104 in PBO, GLM 50 and 100 mg were 1.5, 1.25 and 1.0, respectively. The proportions of pts with changes in TSS greater than the smallest detectable change (SDC) were also maintained from wk52 and wk104. Proportion of pts with no progression (change in TSS≤0) were slightly decrease from wk52 to wk104 in both of GLM 50 mg and 100 mg. Safety finding are also summarized in the Table. Two deaths were reported, one in GLM 50 mg (brain stem haemorrhage) and one in 100 mg (pancreatic carcinoma). Incidences of SAEs and AEs leading to discontinuation in GLM 50 mg were higher than 100 mg. There were no cases of tuberculosis or lymphoma reported.

Conclusion: Treatment with GLM50 mg and 100 mg monotherapy sustained the efficacy of signs/symptoms during 104wks. Inhibition of structural damage in GLM 100 mg was relatively greater than GLM 50mg, however the progression went on slowly during 104wks in both of the GLM groups. The GLM safety profile was similar to other anti-TNF agents.

Evaluation at

PBO ^a)

GLM

50 mg

100 mg

Efficacy results

DAS(ESR) remission (<2.6)

n/N(%)

Wk 52

Wk 104

17/85 ( 20.0)

27/78 ( 34.6)

18/84 ( 21.4)

29/74 ( 39.2)

26/94 ( 27.7)

32/90 ( 35.6)

HAQ remission (<0.5)

n/N(%)

Wk 52

Wk 104

46/85 ( 54.1)

51/78 ( 65.4)

37/84 ( 44.0)

46/74 ( 62.2)

52/94 ( 55.3)

53/90 ( 58.9)

Change from BL in TSS ^b)

Mean (SD)

Median

Wk 52

Wk 104

2.81 (7.139)

1.0

3.61 (8.922)

1.5

3.31 (6.192)

1.0

4.34 (7.720)

1.25

1.56 (5.093)

0.0

2.64 (6.507)

1.0

Pts with progression based on TSS >SDC ^c)

n/N(%)

Wk 52

Wk 104

17/83 ( 20.5)

16/75 ( 21.3)

16/82 ( 19.5)

16/72 ( 22.2)

16/92 ( 17.4)

21/89 ( 23.6)

Pts with change ≤0 in TSS from baseline

n/N(%)

Wk 52

Wk 104

37/105 ( 35.2)

28/75 ( 37.3)

46/101 ( 45.5)

22/72 ( 30.6)

54/102 ( 52.9)

40/89 ( 44.9)

Safety results from all treatment period

Avg duration of follow-up (wks)

15.0

97.1

110.9

Incidence per 100 patient-years (95%CI)

Deaths,

SAEs

Patients with AEs leading to discontinuation

Patients with 1 or more serious infections

0.00 (0.00, 9.88)

6.63 (0.80, 23.94)

9.95 (2.05, 29.09)

3.30 (0.08, 18.38)

0.28 (0.01, 1.55)

14.47 (10.74, 19.08)

7.83 (5.20, 11.32)

3.09 (1.54, 5.53)

0.46 (0.01, 2.56)

7.92 (4.61, 12.68)

5.07 (2.53, 9.07)

3.75 (1.62, 7.39)

a) All patients received placebo crossed over to GLM50 mg afer wk 16.

b) Missing data were imputed using median change from BL of all pts or by linear extrapolation.

c) SDC = 5.18 at wk 52, SDC = 5.65 at wk 104

Disclosure:

T. Takeuchi,