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Abstract

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgements
  9. REFERENCES
  10. Supporting Information

Objective

Golimumab, administered subcutaneously every 4 weeks, has been shown to be effective in reducing the signs and symptoms of active psoriatic arthritis (PsA) through week 24 of the GO-REVEAL study. Herein we report 1-year clinical, radiographic, and safety findings.

Methods

Adult patients with active PsA (≥3 swollen and ≥3 tender joints) were randomly assigned to receive subcutaneous placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks through week 20. At week 16, patients with <10% improvement from baseline in swollen and tender joint counts entered a blinded early escape phase, with placebo crossover to golimumab 50 mg, golimumab 50 mg increased to 100 mg, and golimumab 100 mg continued at 100 mg. Patients receiving placebo who did not enter the early escape phase crossed over to golimumab 50 mg at week 24. Findings through 1 year are reported, including the second of 2 coprimary end points (i.e., change from baseline to week 24 in PsA-modified Sharp/van der Heijde score [SHS]).

Results

A total of 405 patients were randomized: 113 to placebo and 146 each to the golimumab 50 mg and 100 mg groups. Mean changes in PsA-modified SHS from baseline to week 24 for the combined golimumab 50 mg and 100 mg group (−0.09) and the golimumab 50 mg group (−0.16) were significantly different versus placebo (0.27) (P = 0.015 and P = 0.011, respectively). Radiographic benefit was maintained through week 52 with golimumab. Clinical efficacy, including improvement in joint and skin responses and physical function, was maintained through 1 year. The frequency/types of adverse events were similar to those reported through week 24.

Conclusion

Treatment of PsA with golimumab inhibited structural damage progression and demonstrated continued clinical efficacy and safety through 1 year.

Golimumab, a new human anti–tumor necrosis factor (TNF) monoclonal antibody, binds with high affinity and specificity to soluble and transmembrane TNF. Subcutaneous golimumab injections every 4 weeks reduce the signs and symptoms of disease in patients with active rheumatoid arthritis, psoriatic arthritis (PsA), and ankylosing spondylitis (1–6). We previously reported findings for the clinical efficacy and safety of golimumab through week 24 of the GO-REVEAL study, a phase III, multicenter, randomized, double-blind, placebo-controlled study in patients with active PsA (6). At that time, radiographic data had not yet been analyzed. Herein, we report radiographic findings and additional efficacy and safety findings of the GO-REVEAL study through week 52.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgements
  9. REFERENCES
  10. Supporting Information

Patients.

Patients were negative for rheumatoid factor and had active PsA (≥3 swollen joints, ≥3 tender joints, and plaque psoriasis [qualifying lesion of ≥2 cm]) despite therapy with disease-modifying antirheumatic drugs (DMARDs) or nonsteroidal antiinflammatory drugs (NSAIDs). Previous treatment with TNF antagonists, rituximab, natalizumab, or cytotoxic agents was prohibited. Stable doses of methotrexate (MTX; ≤25 mg/week), NSAIDs, and corticosteroids (prednisone ≤10 mg/day) were allowed. Patients with latent tuberculosis could participate if treated prior to or concurrent with the first administration of the study agent (∼11% of patients in both the placebo and golimumab groups required such treatment at study entry). The study was approved by the institutional review board or ethics committee, and written informed consent was obtained from all patients prior to study participation.

Study design.

In this multicenter, randomized, double-blind, placebo-controlled trial, 405 patients were randomized (1:1.3:1.3) by a centralized interactive voice response system (ClinPhone) to receive blinded subcutaneous injections of placebo, golimumab 50 mg, or golimumab 100 mg at weeks 0, 4, 8, 12, 16, and 20. Randomization was stratified by baseline MTX use (yes/no). At week 16, patients with <10% improvement from baseline in both swollen and tender joint counts entered a blinded early escape phase, with crossover from placebo to golimumab 50 mg or dose increase from golimumab 50 mg to 100 mg. Patients in the golimumab 100 mg group who met the early escape criteria continued to receive golimumab 100 mg. Beginning at week 24, patients randomized to placebo who did not enter the early escape phase crossed over to golimumab 50 mg. Thus, all study participants received blinded golimumab 50 mg or 100 mg every 4 weeks from week 24 on. Week 52 was the last evaluation included in the present report. Janssen Research & Development supplied golimumab and placebo as sterile liquids.

Study end points.

The study had 2 coprimary end points: the proportion of patients in whom ≥20% improvement in the American College of Rheumatology response criteria (ACR20) (7) was achieved at week 14 (reported previously) (6) and the change from baseline in PsA-modified Sharp/van der Heijde score (SHS) of the hands and feet at week 24 (reported herein). Radiographs were obtained at baseline, week 24, and week 52 or when study agent was discontinued. Centrally digitized images were scored in random order by 2 independent readers (and an adjudicator in predefined cases) without knowledge of time point, patient identity, or treatment, using a PsA modification of the original SHS (8). To assess PsA-specific radiologic damage, scores for the distal interphalangeal hand joints and pencil-in-cup/gross osteolysis deformities were added to the original SHS. The total PsA-modified SHS (0–528) is a sum of the erosion score (0–320) and joint space narrowing (JSN) score (0–208) in 40 hand joints and 12 foot joints (9). Higher scores and larger increases in radiographic scores indicate more radiographic damage and progression, respectively.

Arthritis activity was assessed by ACR response criteria and the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (10, 11). The extent and severity of psoriasis were assessed by the Psoriasis Area and Severity Index (PASI) score (0–72) (12) among patients with ≥3% of body surface area affected by psoriasis at baseline. Physical function and health-related quality of life were measured using the disability index of the Health Assessment Questionnaire (HAQ) (13) and the Short Form 36 (SF-36) health survey (14), respectively. The proportions of patients with ≥0.3-unit improvement in the HAQ, a clinically important change for PsA patients (15), and changes in physical component summary (PCS) and mental component summary (MCS) scores of the SF-36 were determined. Nail psoriasis was assessed in patients with fingernail psoriasis involvement at baseline using the Nail Psoriasis Severity Index (NAPSI) (16). Dactylitis was assessed in the 20 digits of the hands and feet on a scale of 0–3 (where 0 = no dactylitis and 3 = severe dactylitis). Entheses tenderness was scored in 15 body sites as either absent (0) or present (1) using the PsA-modified Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) (17) (with the left and right insertion of the plantar fascia added).

Safety evaluations included adverse events (AEs) and routine laboratory analyses. Serum samples were collected prior to each injection for determining the presence of antibodies to golimumab (1) and trough golimumab concentrations.

Statistical analysis.

As previously reported (6), the planned sample size (n = 396 [110 placebo and 286 combined golimumab]) provided >98% power to detect a significant difference (α = 0.05) between the placebo and combined golimumab groups in the coprimary efficacy end points. Greater than usual power resulted from basing calculations on radiographic changes and International Committee on Harmonization requirements for numbers of treated patients (18).

The analysis of structural damage was performed as a coprimary end point and was contingent upon the success of the week-14 ACR20 analysis (6). This sequential testing scheme was adopted to protect against Type I error. Changes from baseline to week 24 in total PsA-modified SHS (average score of both primary readers, except for 3 patients with adjudicated scores for whom the averages of the adjudicator and reader with the closest score were used) of the hands and feet for the combined golimumab group (patients receiving 50 mg plus patients receiving 100 mg) were assessed using analysis of variance on the van der Waerden normal scores with treatment and baseline MTX usage (yes/no) as factors in the model. If the results were significant, then pairwise tests were performed for the individual golimumab groups. For this coprimary end point to be considered statistically significant, significant differences were required between the combined golimumab and placebo groups and between ≥1 golimumab dose and the placebo group. All tests were 2-tailed (α = 0.05).

For changes from baseline to week 24 (coprimary end point) and week 52 in total PsA-modified SHS, missing radiographic data were imputed using linear extrapolation. If data were insufficient for linear extrapolation, the median change in total PsA-modified SHS from baseline to week 24 or week 52, within the appropriate MTX stratum, was used to replace the missing data. Patients who entered the early escape phase were analyzed within their randomized group. All remaining radiographic analyses were based on randomized group with no imputation for missing data. In response to a reviewer request, analyses were also performed to assess radiographic response within the subgroups of patients receiving MTX and those not receiving MTX at baseline.

As prespecified, ACR20, ACR50, ACR70, DAS28-CRP, PASI75 (≥75% improvement in PASI), NAPSI (in patients with nail involvement at baseline), enthesitis score (in patients with enthesitis at baseline), dactylitis score (in patients with dactylitis at baseline), HAQ, and SF-36 findings at 1 year were analyzed by treatment received and no data imputation. Post hoc intent-to-treat (ITT) analyses were also performed for these end points, in which patients were assessed by randomized treatment group (patients who entered the early escape phase or crossed over to active treatment remained within their randomized group) and the last observation carried forward method was used for imputation of missing data. In the post hoc analysis of ACR and DAS28-CRP data, patients who discontinued treatment due to lack of efficacy (through week 52) or in whom treatment with DMARDs, corticosteroids, or biologic/immunosuppressive agents was initiated, or the dose of MTX or corticosteroids for PsA was increased before week 24, were considered nonresponders. Results of the ITT analyses are presented herein for the ACR improvement criteria, DAS28-CRP, PASI75, NAPSI, enthesitis, dactylitis, HAQ, and SF-36 assessments.

All patients who received ≥1 dose of golimumab through 1 year were included in safety analyses. Safety events in patients originally randomized to placebo that occurred during receipt of placebo were reported previously (6).

RESULTS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgements
  9. REFERENCES
  10. Supporting Information

Disposition and baseline characteristics of the patients.

As reported previously (6), 405 adults were randomly assigned to receive study agent in the GO-REVEAL study. Consent was obtained from the first patient on December 12, 2005; the last patient completed the final visit for the week-52 reporting period on November 15, 2007. Baseline characteristics indicated active disease with no relevant differences between treatment groups (Table 1). The mean ± SD (median) baseline total PsA-modified SHS was also consistent across treatment groups, ranging from 18.15 ± 27.76 (9.00) to 23.85 ± 35.41 (10.50) (Table 1). Approximately half of all randomized patients received MTX at baseline.

Table 1. Baseline characteristics of the patients with PsA*
 Placebo (n = 113)Golimumab 50 mg (n = 146)Golimumab 100 mg (n = 146)
  • *

    Except where indicated otherwise, values are the mean ± SD. PsA = psoriatic arthritis; CRP = C-reactive protein; DAS28-CRP = Disease Activity Score in 28 joints using the CRP level; SHS = Sharp/van der Heijde score; JSN = joint space narrowing; BSA = body surface area; PASI = Psoriasis Area and Severity Index; NAPSI = Nail Psoriasis Severity Index; MASES = Maastricht Ankylosing Spondylitis Enthesitis Score; HAQ = Health Assessment Questionnaire; SF-36 = Short Form 36; PCS = physical component summary; MCS = mental component summary; MTX = methotrexate.

Sex, no. (%) male69 (61)89 (61)86 (59)
Race, no. (%) white110 (97)141 (97)142 (97)
Age, years47.00 ± 10.5645.70 ± 10.7048.20 ± 10.93
PsA duration, years7.64 ± 7.947.23 ± 6.817.70 ± 7.79
Number of swollen joints (66 assessed)13.40 ± 9.7814.10 ± 11.4012.00 ± 8.45
Number of tender joints (68 assessed)21.90 ± 14.6824.00 ± 17.0622.50 ± 15.71
CRP, mg/dl1.26 ± 1.561.31 ± 1.621.38 ± 1.78
DAS28-CRP4.85 ± 1.024.96 ± 1.104.89 ± 1.06
PsA-modified SHS of hands and feet   
 Erosion score (0–320 scale)10.63 ± 16.1113.73 ± 19.6314.13 ± 21.22
 JSN score (0–208 scale)7.52 ± 12.4710.12 ± 16.789.24 ± 15.02
 Total score (0–528 scale)18.15 ± 27.7623.85 ± 35.4123.37 ± 35.38
No. (%) of patients with ≥3% BSA affected79 (70)109 (75)108 (74)
 BSA affected, %14.7 ± 15.7416.2 ± 17.7417.7 ± 18.34
 PASI score (0–72 scale)8.38 ± 7.389.75 ± 8.5911.11 ± 9.50
No. (%) of patients with fingernail involvement83 (73)95 (65)109 (75)
 No. fingernails6.3 ± 3.46.7 ± 3.46.2 ± 3.4
 Target nail NAPSI score (1–8 scale)4.4 ± 2.24.7 ± 2.24.6 ± 2.1
Patients with dactylitis, no. (%)38 (34)50 (34)49 (34)
 Dactylitis score (1–60 scale)3.1 ± 2.16.3 ± 6.15.4 ± 6.7
Patients with enthesitis, no. (%)88 (78)109 (75)115 (79)
 PsA-modified MASES score (1–15 scale)5.0 ± 4.15.7 ± 4.06.1 ± 4.1
HAQ score (0–3 scale)1.03 ± 0.550.98 ± 0.651.05 ± 0.62
SF-36 health survey   
 PCS score (0–100 scale)31.93 ± 9.2533.03 ± 10.6832.79 ± 8.90
 MCS score (0–100 scale)47.59 ± 10.6945.36 ± 12.2345.03 ± 11.73
Patients taking MTX, no. (%)54 (48)71 (49)69 (47)
 Mean (median) MTX dose, mg/week15.0 (15.0)14.8 (15.0)15.5 (15.0)

At week 52, 360 (89%) of 405 randomized patients continued study participation (including safety followup of patients who discontinued study agent), and 358 (88%) continued to receive study agent (Figure 1). Radiographic images obtained at baseline, week 24, and week 52 were available for 400, 382, and 358 patients, respectively. Three patients had radiographic scores adjudicated according to predefined criteria prior to unblinding of radiographic data.

thumbnail image

Figure 1. Patient disposition through week 52. In the group of patients receiving golimumab 100 mg every 4 weeks (q4 weeks), 25 patients met the early escape (EE) criteria at week 16 and continued to receive golimumab 100 mg.

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Efficacy.

Radiographic response.

The radiograph readers demonstrated good agreement in scoring radiographic images, with intraclass correlation coefficients of 0.94, 0.93, and 0.93 at baseline, week 24, and week 52, respectively. For the coprimary radiographic end point of change from baseline to week 24 in the total PsA-modified SHS, 34 (8.4%) of the 405 randomized patients had missing data. These data were imputed using median change from baseline within the same stratum (for 11 patients in the placebo group, 11 patients in the golimumab 50 mg group, and 7 patients in the golimumab 100 mg group) or by linear extrapolation (for 0 patients in the placebo group, 3 patients in the golimumab 50 mg group, and 2 patients in the golimumab 100 mg group).

For the coprimary end point of change from baseline in PsA-modified SHS at week 24, the mean ± SD change from baseline indicated significantly less radiographic progression in patients receiving golimumab 50 mg (−0.16 ± 1.31) than placebo (0.27 ± 1.26) (P = 0.011) (Table 2). The difference between the golimumab 100 mg group (−0.02 ± 1.32) and the placebo group at week 24 approached statistical significance (P = 0.086). In analyses that assessed changes from baseline to week 24 in the PsA-modified SHS by baseline MTX use, changes in scores indicated less radiographic progression for both golimumab doses (−0.34 ± 1.10 for 50 mg and −0.16 ± 1.36 for 100 mg) versus placebo (0.22 ± 1.25) within the subgroup of patients receiving MTX at baseline than in patients receiving golimumab alone (0.01 ± 1.47 for 50 mg and 0.11 ± 1.28 for 100 mg versus 0.31 ± 1.28 for placebo) (Table 3).

Table 2. Summary of radiographic and clinical efficacy findings by randomized treatment group*
 Placebo (n = 113)Golimumab 50 mg (n = 146)Golimumab 100 mg (n = 146)Golimumab combined (n = 292)
  • *

    ACR = American College of Rheumatology (see Table 1 for other definitions).

  • The placebo group includes patients who changed treatment to golimumab 50 mg at week 16 by meeting early escape criteria and at week 24 via crossover, and the golimumab 50 mg group includes patients who met the early escape criteria at week 16 and changed to golimumab 100 mg.

  • Coprimary study end point. The median change was 0 in all cases.

  • §

    Excludes patients with a missing score at week 24. Values are for new erosions or new JSN in joints with a score of 0 at baseline.

  • The smallest detectable change (SDC) for the PsA-modified SHS was 1.56 for total score, 1.18 for erosion score, and 0.96 for JSN score.

  • #

    Responders were predefined as patients in whom a good or moderate DAS28-CRP score was achieved.

  • **

    Assessed among patients with ≥3% of BSA with psoriasis involvement at baseline.

Change in PsA-modified SHS, baseline to week 24    
 Total score (0–528 scale)    
  n113146146292
  Mean ± SD0.27 ± 1.26−0.16 ± 1.31−0.02 ± 1.32−0.09 ± 1.32
  P vs. placebo 0.0110.0860.015
 Hands    
  n102133138271
  Erosion score (0–200 scale)    
   Mean ± SD0.17 ± 0.88−0.07 ± 0.70−0.09 ± 0.75−0.08 ± 0.72
   P vs. placebo 0.0390.0150.008
  JSN score (0–160 scale)    
   Mean ± SD−0.05 ± 0.38−0.07 ± 0.46−0.06 ± 0.47−0.06 ± 0.46
   P vs. placebo 0.7060.7990.924
  Total hands score (0–360 scale)    
   Mean ± SD0.12 ± 1.08−0.14 ± 0.94−0.15 ± 1.09−0.15 ± 1.02
   P vs. placebo 0.0470.0560.023
 Feet    
  n102132137269
  Erosion score (0–120 scale)    
   Mean ± SD0.16 ± 0.42−0.01 ± 0.530.02 ± 0.560.00 ± 0.54
   P vs. placebo 0.0040.0080.002
  JSN score (0–48 scale)    
   Mean ± SD0.02 ± 0.610.03 ± 0.330.10 ± 0.430.07 ± 0.39
   P vs. placebo 0.8780.2120.420
  Total feet score (0–168 scale)    
   Mean ± SD0.18 ± 0.860.02 ± 0.690.12 ± 0.770.07 ± 0.73
   P vs. placebo 0.0980.3880.150
Additional radiographic findings at week 24    
 Patients with ≥1 uninvolved joint at baseline§    
  n102132138270
  No new erosions    
   No. (%)73 (71.6)115 (87.1)123 (89.1)238 (88.1)
   P vs. placebo 0.003<0.001<0.001
  No new JSN    
   No. (%)90 (88.2)128 (97.0)133 (96.4)261 (96.7)
   P vs. placebo 0.0080.0130.001
 Radiographic progression based on SDC    
  n102132137269
  Total PsA-modified SHS    
   No. (%)11 (10.8)5 (3.8)8 (5.8)13 (4.8)
   P vs. placebo 0.0300.1460.030
  Erosion score    
   No. (%)13 (12.7)6 (4.5)6 (4.4)12 (4.5)
   P vs. placebo 0.0210.0150.004
  JSN score    
   No. (%)3 (2.9)6 (4.5)10 (7.3)16 (5.9)
   P vs. placebo 0.5560.1530.259
 Patients with change from baseline in total PsA-modified SHS ≤0    
  n102132137269
  No. (%)64 (62.7)104 (78.8)105 (76.6)209 (77.7)
  P vs. placebo 0.0070.0200.003
Change in total PsA-modified SHS, baseline to week 52    
 n113146146292
 Mean ± SD0.22 ± 1.38−0.22 ± 1.64−0.14 ± 1.53−0.18 ± 1.59
Week 52 clinical efficacy findings    
 ACR response    
  ACR20, no. (%)74 (65.5)98 (67.1)104 (71.2)202 (69.2)
  ACR50, no. (%)44 (38.9)71 (48.6)74 (50.7)145 (49.7)
  ACR70, no. (%)22 (19.5)52 (35.6)44 (30.1)96 (32.9)
 DAS28-CRP    
  Mean ± SD change from baseline−1.67 ± 1.19−2.02 ± 1.34−1.20 ± 1.21−2.01 ± 1.28
  No. (%) responders#91 (80.5)119 (81.5)121 (82.9)240 (82.2)
 HAQ    
  Mean ± SD change from baseline0.37 ± 0.560.41 ± 0.530.43 ± 0.530.42 ± 0.53
  No. (%) with ≥0.3-unit improvement58 (51.3)73 (50.0)81 (55.5)154 (52.7)
 SF-36    
  Mean ± SD change from baseline in PCS score8.25 ± 10.509.87 ± 9.519.19 ± 10.299.53 ± 9.90
  Mean ± SD change from baseline in MCS score3.69 ± 11.233.95 ± 11.734.84 ± 11.604.40 ± 11.7
 PASI**    
  No. of patients with ≥3% BSA with psoriasis79109108217
  No. (%) with PASI75 response38 (48.1)68 (62.4)74 (68.5)142 (65.4)
 Dactylitis score    
  No. of patients with dactylitis at baseline38504999
  Mean ± SD change from baseline−1.68 ± 2.79−4.20 ± 4.81−4.55 ± 6.60−4.37 ± 5.74
  Mean ± SD % change from baseline57.2 ± 81.270.4 ± 59.983.0 ± 45.976.6 ± 53.5
 Enthesitis score (modified MASES index)    
  No. of patients with enthesitis at baseline88109115224
  Mean ± SD change from baseline−2.08 ± 3.10−3.04 ± 3.57−3.39 ± 3.97−3.22 ± 3.77
  Mean ± SD % change from baseline39.1 ± 76.156.3 ± 62.451.9 ± 64.254.1 ± 63.2
 NAPSI score    
  No. of patients with nail involvement at baseline8395109204
  Mean ± SD change from baseline−2.65 ± 2.33−2.19 ± 2.29−3.25 ± 2.50−2.75 ± 2.46
  Mean ± SD % change from baseline56.2 ± 48.151.6 ± 46.865.8 ± 51.959.2 ± 50.0
Table 3. Summary of radiographic findings by randomized treatment group and baseline MTX use*
 Placebo (n = 113)Golimumab 50 mg (n = 146)Golimumab 100 mg (n = 146)Golimumab combined (n = 292)
  • *

    SDC = smallest detectable change (see Table 1 for other definitions).

  • The placebo group includes patients who changed treatment to golimumab 50 mg at week 16 by meeting early escape criteria and at week 24 via crossover, and the golimumab 50 mg group includes patients who met the early escape criteria at week 16 and changed to golimumab 100 mg.

  • The median change was 0 in all cases.

  • §

    For MTX at baseline versus no MTX at baseline, P = 0.809 in the placebo group, P = 0.028 in the golimumab 50 mg group, P = 0.734 in the golimumab 100 mg group, and P = 0.548 in the combined golimumab group.

  • Excludes patients with a missing score at week 24. Values are for new erosions or new JSN in joints with a score of 0 at baseline.

Change in PsA-modified SHS, baseline to week 24    
 Total score§    
  MTX at baseline    
   n557171142
   Mean ± SD0.22 ± 1.25−0.34 ± 1.10−0.16 ± 1.36−0.25 ± 1.23
   P vs. placebo 0.0030.0980.007
  No MTX at baseline    
   n587575150
   Mean ± SD0.31 ± 1.280.01 ± 1.470.11 ± 1.280.06 ± 1.38
   P vs. placebo 0.4950.3400.350
 Hands    
  Erosion score    
   MTX at baseline    
    n536668134
    Mean ± SD0.22 ± 1.10−0.15 ± 0.82−0.21 ± 0.86−0.18 ± 0.84
    P vs. placebo 0.0600.0190.011
   No MTX at baseline    
    n496770137
    Mean ± SD0.10 ± 0.570.00 ± 0.540.02 ± 0.610.01 ± 0.58
    P vs. placebo 0.3540.2990.264
  JSN score    
   MTX at baseline    
    n536668134
    Mean ± SD−0.06 ± 0.45−0.12 ± 0.45−0.14 ± 0.63−0.13 ± 0.54
    P vs. placebo 0.3450.4200.311
   No MTX at baseline    
    n496770137
    Mean ± SD−0.04 ± 0.30−0.01 ± 0.470.03 ± 0.210.01 ± 0.36
    P vs. placebo 0.6450.1480.281
  Total hands score    
   MTX at baseline    
    n536668134
    Mean ± SD0.17 ± 1.35−0.27 ± 1.05−0.36 ± 1.36−0.31 ± 1.21
    P vs. placebo 0.0380.0140.007
   No MTX at baseline    
    n496770137
    Mean ± SD0.06 ± 0.69−0.01 ± 0.810.05 ± 0.700.02 ± 0.75
    P vs. placebo 0.4920.8900.640
 Feet    
  Erosion score    
   MTX at baseline    
    n536567132
    Mean ± SD0.07 ± 0.28−0.04 ± 0.430.03 ± 0.4600.00 ± 0.44
    P vs. placebo 0.0510.4930.130
   No MTX at baseline    
    n496770137
    Mean ± SD0.26 ± 0.520.01 ± 0.610.01 ± 0.640.01 ± 0.62
    P vs. placebo 0.0320.0040.005
  JSN score    
   MTX at baseline    
    n536567132
    Mean ± SD−0.01 ± 0.32−0.05 ± 0.210.07 ± 0.390.02 ± 0.32
    P vs. placebo 0.2510.4750.475
   No MTX at baseline    
    n496770137
    Mean ± SD0.05 ± 0.820.11 ± 0.410.12 ± 0.460.12 ± 0.43
    P vs. placebo 0.2820.3400.245
  Total feet score    
   MTX at baseline    
    n536567132
    Mean ± SD0.06 ± 0.47−0.08 ± 0.530.10 ± 0.590.01 ± 0.57
    P vs. placebo 0.0970.7860.397
   No MTX at baseline    
    n496770137
    Mean ± SD0.31 ± 1.130.13 ± 0.810.13 ± 0.900.13 ± 0.86
    P vs. placebo 0.4500.1660.216
Additional radiographic findings at week 24    
 No new erosions among patients with ≥1 uninvolved joint at baseline    
  MTX at baseline    
   No. (%)36/53 (67.9)58/65 (89.2)62/68 (91.2)120/133 (90.2)
   P vs. placebo 0.0040.001<0.001
  No MTX at baseline    
   No. (%)37/49 (75.5)57/67 (85.1)61/70 (87.1)118/137 (86.1)
   P vs. placebo 0.1940.1010.087
 No new JSN among patients with ≥1 uninvolved joint at baseline    
  MTX at baseline    
   No. (%)48/53 (90.6)64/65 (98.5)68/68 (100.0)132/133 (99.2)
   P vs. placebo 0.0520.0100.002
  No MTX at baseline    
   No. (%)42/49 (85.7)64/67 (95.5)65/70 (92.9)129/137 (94.2)
   P vs. placebo 0.0630.2030.062
 Radiographic progression based on change from baseline > SDC    
  Total PsA-modified SHS    
  MTX at baseline    
   No. (%)4/53 (7.5)0/65 (0.0)2/67 (3.0)2/132 (1.5)
   P vs. placebo 0.0240.2550.036
  No MTX at baseline    
   No. (%)7/49 (14.3)5/67 (7.5)6/70 (8.6)11/137 (8.0)
   P vs. placebo 0.2330.3250.204
  Erosion score    
  MTX at baseline    
   No. (%)5/53 (9.4)2/65 (3.1)1/67 (1.5)3/132 (2.3)
   P vs. placebo 0.1460.0470.030
  No MTX at baseline    
   No. (%)8/49 (16.3)4/67 (6.0)5/70 (7.1)9/137 (6.6)
   P vs. placebo 0.0700.1140.042
  JSN score    
  MTX at baseline    
   No. (%)1/53 (1.9)1/65 (1.5)3/67 (4.5)4/132 (3.0)
   P vs. placebo 0.8840.4320.665
  No MTX at baseline    
   No. (%)2/49 (4.1)5/67 (7.5)7/70 (10.0)12/137 (8.8)
   P vs. placebo 0.4500.2290.287
 Patients with change from baseline in total PsA-modified SHS ≤0    
  MTX at baseline    
   No. (%)32/53 (60.4)55/65 (84.6)52/67 (77.6)107/132 (81.1)
   P vs. placebo 0.0030.0410.003
  No MTX at baseline    
   No. (%)32/49 (65.3)49/67 (73.1)53/70 (75.7)102/137 (74.5)
   P vs. placebo 0.3640.2160.221
Change in PsA-modified SHS, baseline to week 52    
 MTX at baseline    
  n557171142
  Mean ± SD0.06 ± 1.23−0.52 ± 1.46−0.38 ± 1.82−0.45 ± 1.65
 No MTX at baseline    
  n587575150
  Mean ± SD0.37 ± 1.510.05 ± 1.760.09 ± 1.160.07 ± 1.49

All sensitivity analyses conducted for the radiographic coprimary end point confirmed the robustness of the primary analysis. These analyses included: 1) 350 patients who received all scheduled treatments and had baseline and week-24 radiographic readings, 2) patients without change in treatment during the early escape phase (62 patients in the placebo group, 118 patients in the golimumab 50 mg group, and 146 patients in the golimumab 100 mg group), and 3) all 405 randomized patients with images read by primary readers only (without adjudication). In probability plots of the change from baseline to week 24 in total PsA-modified SHS in patients in the placebo and golimumab 50 mg groups, separation of groups indicating greater radiographic progression in patients treated with placebo versus patients treated with golimumab 50 mg was more evident in patients receiving MTX at baseline (Figure 2A) than in those not receiving MTX at baseline (Figure 2B).

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Figure 2. Cumulative distribution function plot of the change from baseline to week 24 in the total psoriatic arthritis–modified Sharp/van der Heijde score (SHS) among A, patients who were receiving methotrexate (MTX) at baseline and B, patients who were not receiving MTX at baseline. Primary analysis rules were applied.

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The findings of secondary radiographic analyses conducted through week 24 also supported inhibition of structural damage in golimumab-treated patients. Patients receiving golimumab 50 mg and those receiving golimumab 100 mg had significantly less change from baseline in hand/foot erosion scores than patients receiving placebo (Figure 3), and the golimumab treatment groups had significantly more patients with no new erosions or JSN (among patients with baseline erosion/JSN scores of 0) than the placebo group (Table 2). Significantly fewer patients in the golimumab 50 mg group had radiographic progression defined by change in total PsA-modified SHS greater than the smallest detectable change (SDC; 1.56), and significantly more patients in the golimumab 50 mg and 100 mg groups had no progression in radiographic scores, defined by change from baseline in the total PsA-modified SHS ≤0, versus placebo (Table 2). For all of these secondary radiographic end points, treatment group differences were generally enhanced in patients receiving MTX at baseline compared with those not receiving MTX at baseline (Table 3).

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Figure 3. Mean ± SEM change from baseline to week 52 in the psoriatic arthritis–modified Sharp/van der Heijde score. A, Total score. P = 0.011, golimumab 50 mg versus placebo; P = 0.086, golimumab 100 mg versus placebo. B, Erosion score. P < 0.001, golimumab 50 mg versus placebo; P = 0.001, golimumab 100 mg versus placebo. C, Joint space narrowing (JSN) score. There were no significant differences for JSN score. Of note, all patients randomized to the placebo group were receiving golimumab 50 mg starting at week 24.

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Radiographic data through week 52 demonstrated maintenance of radiographic benefit among golimumab-treated patients, as well as some improvement in the total PsA-modified SHS among patients who crossed over from placebo to active treatment at week 24 (mean ± SD change from week 24 to week 52 of −0.07 ± 1.36). Patients initially randomized to placebo, however, appeared to have more damage at week 52 than patients initially randomized to golimumab (Figure 3). Few patients had pencil-in-cup or gross osteolysis deformities at baseline, and this remained unchanged during the first year of golimumab treatment.

ACR response.

As previously reported (6), an ACR20 response was achieved at week 14 (a coprimary end point) in significantly higher proportions of patients in the golimumab 50 mg group (51%) and 100 mg group (45%) than in the placebo group (9%) (P < 0.001). Results of an ITT analysis at week 52 indicated that among patients randomized to placebo (including those who entered the early escape phase to receive golimumab 50 mg at week 16 or crossed over to golimumab 50 mg at week 24 per protocol), golimumab 50 mg (including those who entered the early escape phase to receive golimumab 100 mg at week 16), and golimumab 100 mg, an ACR20 response was achieved in 66%, 67%, and 71%, respectively; an ACR50 response was achieved in 39%, 49%, and 51%, respectively; and an ACR70 response was achieved in 20%, 36%, and 30%, respectively, of patients (Table 2).

DAS28-CRP.

A DAS28-CRP response of good or moderate was achieved in 81%, 82%, and 83% of all patients randomized to placebo, golimumab 50 mg, and golimumab 100 mg, respectively, at week 52, according to an ITT analysis (Table 2). Changes from baseline in DAS28-CRP scores are summarized in Table 2.

Skin, nails, enthesitis, and dactylitis.

Results of ITT analyses indicated that a PASI75 response was achieved at week 52 in 48%, 62%, and 69% of the patients with baseline psoriasis involvement of ≥3% of body surface area who were randomized to placebo, golimumab 50 mg, and golimumab 100 mg, respectively. Improvements from baseline to week 52 were also observed for NAPSI, modified MASES, and dactylitis scores (Table 2).

Physical function and quality of life.

Based on an ITT analysis, mean ± SD improvements from baseline to week 52 in HAQ score were 0.37 ± 0.56, 0.41 ± 0.53, and 0.43 ± 0.53 for patients randomized to placebo, golimumab 50 mg, and golimumab 100 mg, respectively. In addition, 51%, 50%, and 56% of patients randomized to placebo, golimumab 50 mg, and golimumab 100 mg, respectively, had a clinically meaningful improvement (≥0.3 unit) in HAQ from baseline to week 52 (Table 2).

Also based on an ITT analysis of patients randomized to placebo, golimumab 50 mg, and golimumab 100 mg, mean ± SD improvements from baseline to week 52 in SF-36 PCS scores were 8.25 ± 10.50, 9.87 ± 9.51, and 9.19 ± 10.29, respectively, and in SF-36 MCS scores were 3.69 ± 11.23, 3.95 ± 11.73, and 4.84 ± 11.60, respectively (Table 2).

Post hoc analyses were conducted to assess the effect of baseline MTX use on clinical efficacy (data not shown). In general, comparable clinical response rates were observed between patients who did and those who did not receive MTX at baseline, with slightly greater improvement in NAPSI, dactylitis, and enthesitis scores in patients randomized to golimumab who did receive concomitant MTX (63%, 81%, and 59%, respectively) than in those who did not receive concomitant MTX (56%, 71%, and 50%, respectively).

Safety.

Adverse events.

A summary of AEs through week 52 is provided in Supplementary Table 1, available on the Arthritis & Rheumatism web site at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1529-0131. Note that no patient was exposed to placebo beyond week 24 and that the average duration of followup varied by treatment group (from ∼28 weeks to 51 weeks). The most common AEs in golimumab-treated patients were upper respiratory tract infection and nasopharyngitis. No differences in types of AEs were observed between patients receiving golimumab 50 mg and those receiving golimumab 100 mg, and the proportions of patients with AEs were similar between patient subgroups that were and those that were not receiving MTX at baseline. Infections occurred in 23 (45%), 18 (35%), 68 (47%), 9 (32%), and 84 (58%) of the patients who received placebo and then golimumab 50 mg after entering the early escape phase, patients who received placebo and then golimumab 50 mg after crossover at week 24, patients who received golimumab 50 mg only, patients who received golimumab 50 mg followed by 100 mg, and patients who received golimumab 100 mg, respectively.

Serious AEs were reported for 2 (4%), 9 (6%), 2 (7%), and 5 (3%) of the patients who received placebo and then golimumab 50 mg after entering the early escape phase at week 16, patients who received golimumab 50 mg only, patients who received golimumab 50 mg and then 100 mg, and patients who received golimumab 100 mg, respectively. Three patients had serious infections. Of these, 2 patients were receiving golimumab 50 mg only (abscess, superficial thrombophlebitis), and 1 patient was receiving golimumab 100 mg (sepsis, acute cholecystitis). No patient developed active tuberculosis or an opportunistic infection through week 52.

Overall, 14 (4%) of the golimumab-treated patients discontinued study agent because of an AE, including 2 (4%), 5 (3%), and 7 (5%) of the patients who received placebo and then golimumab 50 mg after entering the early escape phase at week 16, patients who received golimumab 50 mg only, and patients who received golimumab 100 mg, respectively. AEs resulting in discontinuation of study agent generally occurred in 1 patient only. Exceptions included increased alanine aminotransferase (ALT) in 3 patients (in 1 patient receiving placebo and then golimumab 50 mg after entering the early escape phase at week 16 and in 2 patients receiving golimumab 50 mg only), increased aspartate aminotransferase (AST) in 2 patients (both receiving golimumab 50 mg only), and basal cell carcinoma in 2 patients (both receiving golimumab 100 mg).

Through week 52, two patients, both randomized to golimumab 50 mg, died: 1 from a climbing accident and 1 from small cell lung cancer. In addition to this malignancy and the 2 patients with basal cell skin carcinomas (discussed above), 2 additional patients had malignancies. One patient (receiving golimumab 100 mg) had prostate cancer, and the other (receiving placebo and then golimumab 50 mg after entering the early escape phase) had colon cancer (see Supplementary Table 1, available on the Arthritis & Rheumatism web site at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1529-0131).

Injection site reactions, most commonly injection site erythema, occurred in 1 (2%), 5 (10%), 11 (8%), and 13 (9%) of the patients who received placebo and then golimumab 50 mg after entering the early escape phase at week 16, patients who received placebo and then golimumab 50 mg after crossover, patients who received golimumab 50 mg only, and patients who received golimumab 100 mg, respectively (see Supplementary Table 1, available on the Arthritis & Rheumatism web site at http://onlinelibrary.wiley.com/journal/10.1002(ISSN)1529-0131). No injection site reaction was severe, serious, or resulted in treatment discontinuation. No patient experienced anaphylactic or serum sickness–like reactions.

Laboratory values.

Markedly abnormal changes in clinical laboratory variables were assessed using predefined thresholds for clinically meaningful values and changes from baseline. Few golimumab-treated patients had >1 markedly abnormal postbaseline hematology or chemistry laboratory value (see Supplementary Table 1, available on the Arthritis & Rheumatism web site at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1529-0131). More than half of the patients with total bilirubin, ALT, or AST elevations received concomitant MTX for PsA, and none of them received isoniazid for tuberculosis prophylaxis. No new patients had clinically meaningful concurrent elevations in ALT, AST, or total bilirubin since the time of the week-24 report (6).

Golimumab pharmacokinetics and antibodies to golimumab.

Dose-proportional pharmacokinetics were observed through week 52, and median serum trough golimumab concentrations were generally similar at week 24 and week 52. Consistent with findings through week 24 (6), the incidence of antibodies to golimumab remained low through week 52 (4.9%), with no apparent differences between patients receiving golimumab 50 mg and those receiving golimumab 100 mg (see Supplementary Table 1, available on the Arthritis & Rheumatism web site at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1529-0131). In all cases, antibodies were determined to be neutralizing to golimumab in vitro. The majority of patients with antibodies to golimumab (18 of 19) did not receive concomitant MTX.

DISCUSSION

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgements
  9. REFERENCES
  10. Supporting Information

The efficacy and safety of the human monoclonal anti-TNF agent golimumab, administered subcutaneously every 4 weeks in patients with active PsA, were previously reported through week 24 of the GO-REVEAL study (6). Approximately half of these patients across all treatment groups were receiving MTX at baseline. As previously reported, ACR20, ACR50, ACR70, DAS28-CRP, and PASI75 responses were achieved in significantly more golimumab-treated patients than placebo-treated patients, and significantly more golimumab-treated patients demonstrated improvement in physical function and quality of life at week 24. Differences between patients receiving golimumab 50 mg and those receiving golimumab 100 mg were modest. The current report summarizes 1-year findings for the second of the 2 coprimary end points (change in PsA-modified SHS from baseline to week 24) in the GO-REVEAL study, along with clinical efficacy, radiographic, and safety findings through week 52.

For the coprimary end point of change from baseline in the total PsA-modified SHS at week 24, patients receiving golimumab demonstrated significantly less structural damage progression compared with patients receiving placebo (mean change −0.09 versus 0.27; P = 0.015). For the individual golimumab doses, significantly less radiographic progression was observed with golimumab 50 mg (mean change −0.16) versus placebo (P = 0.011), while the difference between the 100 mg golimumab dose (mean change −0.02) and placebo approached statistical significance (P = 0.086). In this context, the findings of the primary analysis suggest that the 100 mg dose is not superior to the 50 mg dose in inhibiting the progression of structural damage in patients with PsA. Consistent with the results of anti-TNF treatment in rheumatoid arthritis and infliximab treatment in PsA (19), golimumab-treated patients who were receiving concomitant MTX had less radiographic progression than patients who were receiving golimumab alone.

Other radiographic measures of structural damage, such as the proportions of patients with no new erosions or JSN, progression greater than the SDC, and a change in the total radiographic score of ≤0, supported the findings of the primary analyses, indicating that golimumab reduces radiographic progression in patients with PsA, although not necessarily in a dose-dependent manner.

Conducting radiographic imaging at week 52 allowed us to assess radiographic data after 1 year of golimumab treatment. Radiographic benefit was maintained among golimumab-treated patients, and patients who entered the early escape phase at week 16 or crossed over from placebo to golimumab 50 mg by week 24 showed improvement in the total PsA-modified SHS. Similar observations regarding the inhibition of radiographic progression by other anti-TNF agents have also been reported (19–21), suggesting that, as a class, TNF antagonists provide a major advantage to patients with PsA in that they are clearly disease modifying. Moreover, the fact that patients who received placebo, despite decreased progression after having crossed over to active drug, demonstrated more structural damage at week 52 suggests that these medications should be offered to patients with PsA earlier in their disease course to prevent the development and progression of radiologic damage.

The efficacy of golimumab in reducing the signs and symptoms of PsA and improving physical function and quality of life was maintained at week 52. Since ∼11% of the patients ended study participation prior to week 52, analyses based on only the observed data could have resulted in higher response rates. Thus, ACR improvement criteria, DAS28-CRP, PASI, NAPSI, enthesitis, dactylitis, HAQ, and SF-36 data were analyzed post hoc, incorporating all randomized patients and using the last observation carried forward method for imputation of missing data. In addition, for ACR improvement criteria and DAS28-CRP responses, patients who discontinued because of lack of efficacy or who had protocol-prohibited changes in PsA medications were considered nonresponders at week 52. Results obtained using this more conservative analytical approach indicated that relatively large proportions of patients receiving golimumab beginning at week 0 maintained responses at week 52 in both the arthritic component of PsA (67–71% of patients had an ACR20 response and 82–83% of patients had a DAS28-CRP response) and the skin component of PsA (62–69% had a PASI75 response).

Improvements in nail psoriasis, enthesitis, and dactylitis scores were also maintained through week 52, as were clinically meaningful improvements in physical function (HAQ score) and quality of life (SF-36 PCS and MCS scores) in patients randomized to golimumab. Patients who switched from placebo to golimumab 50 mg at week 16 or week 24 generally had similar responses at week 52 to patients who received golimumab from study inception, with the exception of lower PASI75 response rates. Results of a post hoc analysis conducted to assess the effect of concomitant MTX use on clinical efficacy indicated that comparable clinical response rates were generally observed between patients who did and those who did not receive concomitant MTX at baseline, with ∼10% more improvement in NAPSI, dactylitis, and enthesitis scores in patients who received concomitant MTX than in those who did not.

Pharmacokinetic findings at week 52 were similar to those observed at week 24 (6). Through week 52, serum golimumab trough concentrations were proportional to doses and were maintained throughout the study period. The overall incidence of antibodies to golimumab at week 52 (4.9%) was consistent with findings at week 24 (4.6%) (6). Antibodies to golimumab were more commonly observed in patients not receiving MTX at baseline than in those receiving MTX at baseline. All detected antibodies neutralized golimumab activity in vitro.

Safety findings through week 52 were consistent with week-24 results (6) and with those for other biologic agents, including anti-TNF agents, in PsA (19–23). The proportion of patients with ≥1 AE was ∼78% overall and tended to be higher with longer duration of followup. The system organ class with the highest AE incidence remained “infections and infestations,” most commonly upper respiratory infections. Through week 52, ∼5% of golimumab-treated patients had serious AEs, including 3 patients with serious infections and 2 deaths (both patients received golimumab 50 mg; 1 from small cell lung cancer and 1 from an alpine climbing accident). Malignancies were reported in 5 patients: small cell lung cancer (in 1 patient receiving golimumab 50 mg only [as noted above and in Results]), colon cancer (in 1 patient receiving placebo and then golimumab 50 mg after entering the early escape phase at week 16), prostate cancer (in 1 patient receiving golimumab 100 mg), and basal cell carcinoma (in 2 patients receiving golimumab 100 mg). The low number of patients with malignancies and the lack of an adequate control arm beyond week 24 limit the interpretation of analyses conducted to assess the relationship between the treatment regimens and these events.

The main study limitations were the relatively short placebo-controlled period (24 weeks) and changes in dose regimens via placebo crossover to active treatment and/or early escape. While these design features were employed to reduce the effect of potentially inferior treatment regimens on patients, they may have yielded a placebo-controlled period that was insufficient for detecting clinically meaningful differences between the treatment groups in certain aspects of disease, e.g., radiographic progression. In fact, numerically small changes in radiographic scores were observed. These changes, however, are consistent with those reported for other anti-TNF agents in PsA imaging studies and were not unexpected, given the population of patients enrolled in the study and the study design incorporating an early escape mechanism and an early radiographic end point at week 24. Small changes in radiographic scores over short time periods in a chronic disease are believed to eventually lead to large changes over a longer followup period and yield differences in clinically important outcomes, e.g., physical function. Therefore, any structural damage inhibition should be considered clinically relevant. Longer-term data are needed to assess the maintenance of radiographic benefit beyond 1 year.

Overall, GO-REVEAL data through 1 year support the sustained efficacy of subcutaneous golimumab administered every 4 weeks in reducing the signs and symptoms of joint and skin disease in patients with active PsA despite treatment with NSAIDs or DMARDs. Significant inhibition of structural damage at week 24 and maintenance of radiographic benefit and improved physical function through 1 year were also observed. Golimumab efficacy was not substantially different between patients receiving 50 mg and those receiving 100 mg and was comparable to that observed with other commercially available anti-TNF agents (19–23). Golimumab safety data were also consistent across both doses and with safety data for other anti-TNF agents. The GO-REVEAL study continues in an open-label format, and longer-term data beyond week 52 are forthcoming.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgements
  9. REFERENCES
  10. Supporting Information

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Kavanaugh had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Kavanaugh, McInnes, Mease, Gladman, Papp, W. Xu, Mack, Rahman, Z. Xu, Beutler.

Acquisition of data. Kavanaugh, Mease, Gladman, Gómez-Reino, Papp, Baratelle, W. Xu, Zrubek.

Analysis and interpretation of data. Kavanaugh, van der Heijde, McInnes, Mease, Krueger, Gladman, Gómez-Reino, Papp, Baratelle, W. Xu, Mudivarthy, Mack, Rahman, Z. Xu, Zrubek, Beutler.

ROLE OF THE STUDY SPONSOR

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgements
  9. REFERENCES
  10. Supporting Information

Janssen Research & Development, LLC (Spring House, PA) and Merck/Schering-Plough (Kenilworth, NJ) provided funding. The steering committee (AK, IBM, PM, GGK, and DDG) supervised the study and assisted with study design. Clinical data were collected by the investigators and entered into a Janssen database. Radiographic data were collected by Perceptive, Inc. (Waltham, MA) and centrally processed by BioClinica (Newtown, PA). The images were scored by independent readers in a process arranged by BioClinica. Janssen statisticians and programmers conducted the analyses, and steering committee members, with medical writing assistance, prepared the manuscript. All authors reviewed and approved the manuscript before submission and agreed to submit the final version. Richard Cook, PhD (University of Waterloo, Waterloo, Ontario, Canada) evaluated the analyses and content of the manuscript as an independent statistician.

Acknowledgements

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgements
  9. REFERENCES
  10. Supporting Information

The authors thank Michelle Perate, MS, and Mary Whitman, PhD (Janssen Services, LLC) for their writing and editorial support. A complete list of study investigators was previously reported (6).

REFERENCES

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgements
  9. REFERENCES
  10. Supporting Information
  • 1
    Kay J, Matteson EL, Dasgupta B, Nash P, Durez P, Hall S, et al. Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study [published erratum appears in Arthritis Rheum 2010;62:3518]. Arthritis Rheum 2008; 58: 96475.
  • 2
    Emery P, Fleischmann RM, Moreland LW, Hsia EC, Strusberg I, Durez P, et al. Golimumab, a human anti–tumor necrosis factor α monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four–week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis [published erratum appears in Arthritis Rheum 2010;62:3005]. Arthritis Rheum 2009; 60: 227283.
  • 3
    Keystone EC, Genovese MC, Klareskog L, Hsia EC, Hall ST, Miranda PC, et al. Golimumab, a human antibody to tumour necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study [published erratum appears in Ann Rheum Dis 2011;70:238]. Ann Rheum Dis 2009; 68: 78996.
  • 4
    Inman RD, Davis JC Jr, van der Heijde D, Diekman L, Sieper J, Kim SI, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum 2008; 58: 340212.
  • 5
    Smolen JS, Kay J, Doyle MK, Landewe R, Matteson EL, Wollenhaupt J, et al, for the GO-AFTER study investigators. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor α inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial [published erratum appears in Lancet 2009;374:1422]. Lancet 2009; 374: 21021.
  • 6
    Kavanaugh A, McInnes I, Mease P, Krueger GG, Gladman D, Gomez-Reino J, et al. Golimumab, a new human tumor necrosis factor α antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty-four–week efficacy and safety results of a randomized, placebo-controlled study [published erratum appears in Arthritis Rheum 2010;62:2555]. Arthritis Rheum 2009; 60: 97686.
  • 7
    Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995; 38: 72735.
  • 8
    Van der Heijde DM, van Leeuwen MA, van Riel PL, Koster AM, van 't Hof MA, van Rijswijk MH, et al. Biannual radiographic assessments of hands and feet in a three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum 1992; 35: 2634.
  • 9
    Van der Heijde D, Sharp J, Wassenberg S, Gladman DD. Psoriatic arthritis imaging: a review of scoring methods. Ann Rheum Dis 2005; 64 Suppl II: ii614.
  • 10
    Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight–joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38: 448.
  • 11
    Wells G, Becker JC, Teng J, Dougados M, Schiff M, Smolen J, et al. Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis 2009; 68: 95460.
  • 12
    Fredriksson T, Pettersson U. Severe psoriasis—oral therapy with a new retinoid. Dermatologica 1978; 157: 23844.
  • 13
    Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum 1980; 23: 13745.
  • 14
    Ware JE Jr, Sherbourne CD. The MOS 36-item Short-Form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: 47383.
  • 15
    Mease PJ, Ganguly R, Wanke L, Yu E, Singh A. How much improvement in functional status is considered important by patients with active psoriatic arthritis: applying the outcome measures in rheumatoid arthritis clinical trials (OMERACT) group guidelines. Ann Rheum Dis 2004; 63 Suppl I: i391.
  • 16
    Rich P, Scher RK. Nail Psoriasis Severity Index: a useful tool for evaluation of nail psoriasis. J Am Acad Dermatol 2003; 49: 20612.
  • 17
    Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, Landewe R, van der Tempel H, Mielants H, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis 2003; 62: 12732.
  • 18
    International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH): the extent of population exposure to assess clinical safety for drugs intended for long-term treatment of non-life-threatening conditions, E1. Fed Regist 1995; 60: 11270.
  • 19
    Van der Heijde D, Kavanaugh A, Gladman DD, Antoni C, Krueger GG, Guzzo C, et al, for the IMPACT 2 Study Group. Infliximab inhibits progression of radiographic damage in patients with active psoriatic arthritis through one year of treatment: results from the Induction and Maintenance Psoriatic Arthritis Clinical Trial 2. Arthritis Rheum 2007; 56: 2698707.
  • 20
    Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB, Ory P, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum 2004; 50: 226472.
  • 21
    Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, Choy EH, et al, for the Adalimumab Effectiveness in Psoriatic Arthritis Trial Study Group. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2005; 52: 327989.
  • 22
    Gladman DD, Mease PJ, Ritchlin CT, Choy EH, Sharp JT, Ory PA, et al. Adalimumab for long-term treatment of psoriatic arthritis: forty-eight week data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial. Arthritis Rheum 2007; 56: 47688.
  • 23
    Kavanaugh A, Krueger GG, Beutler A, Guzzo C, Zhou B, Dooley LT, et al, for the IMPACT 2 Study Group. Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial. Ann Rheum Dis 2007; 66: 498505.

Supporting Information

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgements
  9. REFERENCES
  10. Supporting Information

Additional Supporting Information may be found in the online version of this article.

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ART_34436_sm_suppltable1.doc49KSupplementary Table 1

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