Skip to main content

Table 2 Included references and results

From: The pharmacological and clinical aspects behind dose loading of biological disease modifying anti-rheumatic drugs (bDMARDs) in auto-immune rheumatic diseases (AIRDs): rationale and systematic narrative review of clinical evidence

Reference

Patient population

Study design

Drug

Groups and dosing regimens

Numbers of patients

Primary outcome

Results primary outcome

Relevant secondary outcomes

Results secondary outcomes

Mease et al., 2011 [12]

Psoriatic Arthritis

Randomized, double-blind, placebo-controlled Phase II trial

Abatacept

Group 1: 3 mg/kg at days 1, 15, and 29, every 4 weeks thereafter

Group 2: 10 mg/kg at days 1, 15, and 29, every 4 weeks thereafter

Group 3: 30 mg/kg at days 1 and 15, 10 mg/kg at day 29 and every 4 weeks thereaftera

Group 1: 43

Group 2: 40

Group 3: 45

ACR20 at 6 months

ACR20

Group 1: 33%

Group 2: 48%

Group 3: 42%

No significant differences reported between the groups (especially groups 2 and 3)

HAQ-DI

SF-36

ACR50

ACR70

Damage of joints on MRI

AE’s

No significant differences reported between the groups (especially groups 2 and 3)

Schiff et al., ACR meeting 2012 [11]

Rheumatoid Arthritis

Randomized study; post-hoc analysis on data from the ACQUIRE and AMPLE studies

Abatacept

Group 1: s.c. 125 mg/week (ACQUIRE)

Group 2: s.c. 125 mg/week, plus i.v. loading dose 10 mg/kg on day 1 (AMPLE)

Group 1: 736 (ACQUIRE)

Group 2: 318 (AMPLE)

ACR20 at weeks 2, 4, 8, 12, 16, 20, 24.

ACR20 at weeks 2, 4, 8, 12, 16, 20, 24

Group 1: 27.4, 42.5, 58.5, 60.1, 66.0, 70.1, 66.0%

Group 2:24.6, 44.5, 58.0, 66.6, 69.3, 72.4, 74.8%

No significant difference between the groups

HAQ-DI at weeks 2, 4, 8, 12, 16, 20, 24

Changes in DAS28 CRP from baseline over 6 months

No significant difference between the groups

Takeuchi et al., Mod Rheumatol 2016 [10]

Rheumatoid Arthritis

Open label extension study; post hoc analysis of the J-RAPID and HIKARI trials

Certolizumab pegol (CZP)

Group 1: 400 mg loading dose at weeks 0, 2, and 4, then 200 mg Q2W thereafter

Group 2: 200 mg Q2W

Group 1: 198

Group 2: 160

ACR20 at weeks 4, 8, 12, 16, 20, 24% Low disease activity

ACR20 at week 4

Group 1: 62.2 and 67.2%

Group 2: 57.1 and 49.5%

ACR20 at week 8

Group 1: 82.9 and 71.6%

Group 2: 69.6 and 61.1%

Absolute values for week 12, 16, 20, and 24 were not provided; graphical presentation only.

No statistical data providedb

Not well defined in methods section, but reported for: ACR50,70 responses

% Low disease activity (LDA) at weeks 12 and 24

Plasma concentrations of CZP and antibodies against CZP

Adverse Events rates

Loading dose groups showed faster ACR responses followed by sustained ACR responses up to 24 weeks compared to patients who did not receive loading dose.

Higher levels of antibodies in group without loading dose.

Similar adverse event rates.

No statistical data provided♠

Mease et al., Ann Rheum Dis, 2018 [13]

Psoriatic Arthritis

Randomised double-blind phase III FUTURE 5 study

Secukinumab

Group 1:

150 mg s.c. with loading dose, at weeks 0, 1, 2, 3 and 4, then every 4 weeks thereafter

Group 2: 150 mg s.c. without loading dose, at weeks 0, (at 1, 2, 3 placebo) and 4, then every 4 weeks thereaftera

Group 1: 222

Group 2: 220

ACR20 at week 16

ACR20 response at week 16

Group 1: 55.5%

Group 2: 59.5%

No statistical difference between loading versus no loading

Radiographic progression at week 24 (van der Heijde-modified total Sharp score)

HAQ-DI

DAS28-CRP

ACR50/70 response

Proportion of patients achieving MDA at week 16

AE’s and SAE’s

No statistical difference between loading versus no loading

Kivitz et al., Rheumatol Ther, 2018 [14]

Ankylosing Spondylitis

Randomized placebo controlled trial

MEASURE 4 study

Secukinumab

Group 1: 150 mg at week 0 and every 4 weeks thereafter, with loading dose 150 mg at weeks 1, 2, and 3

Group 2: 150 mg at week 0 and every 4 weeks thereafter, with placebo at weeks 1, 2, and 3

Group 1: 116

Group 2: 117

ASAS20 at 16 weeks

ASAS20 at 16 weeks

Group 1: 59.5%

Group 2: 61.5%

No significant difference.

ASAS20 at 52, and 104 weeks

ASAS40 at 16 weeks

% achieving ASAS20 and ASAS40

Change from baseline in BASDAI % AEs, % SAEs

No significant difference

  1. a Placebo groups were removed from the table [12, 13]
  2. b Exact patient numbers in each group at each time point could not be extracted from the manuscript for post hoc statistical analysis
  3. Abbreviations:
  4. ACR American College of Rheumatology (ACR20 means 20% improvementin tender or swollen joint counts as well as 20% improvement in three of the other five criteria; ACR50 70 analogous)
  5. HAQ-DI Health Assessment Questionnaire, Disability Index
  6. SF36 Short Form 36
  7. ASAS Assessment in Spondyloarthritis International Society
  8. Q2W Every two weeks
  9. DAS28 CRP Disease Activity Score based on 28 joints and C-reactive protein
  10. BASDAI Bath Ankylosing Spondylitis Disease Activity Index
  11. MDA Minimal Disease Activity
  12. (S)AE (Serious) Adverse Events
  13. CZP Certolizumab pegol