ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 597

Characteristics of Patients and Predictors of Composite Disease Activity Scores for Switching to Monotherapy Vs Continuing TNF Inhibitor and Methotrexate Combination Therapy in RA: A Retrospective Analysis of the Brigham and Women’s Rheumatoid Arthritis Sequential Study Registry

Nancy A. Shadick1, Michael E Weinblatt1, Christine K Iannaccone2, Michelle Frits3, Tigwa Davis4, Christopher Young4, David H. Collier5, Mahdi Gharaibeh5 and Bradley S. Stolshek6, 1Brigham and Women's Hospital, Boston, MA, 2Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 3Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 4Health Analytics, LLC, Columbia, MD, 5Amgen Inc., Thousand Oaks, CA, 6Amgen, Inc., Thousand Oaks, CA

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , , , ,

Session Information

Date: Sunday, October 21, 2018

Title: Rheumatoid Arthritis – Treatments Poster I: Strategy and Epidemiology

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Biologics in combination with methotrexate (MTX) are being incorporated earlier in rheumatoid arthritis (RA) therapy to prevent long-term damage and maintain patient function. While some patients transition off TNF inhibitor (TNFi) + MTX combination therapy (Combo) to monotherapy (TNFi mono or MTX mono), differences in patient characteristics and attainment of disease control for the Combo and monotherapy groups are unclear.

Methods: Data were obtained from a prospectively collected cohort at a single academic medical center from 2003 to 2016. At study visits every 6 months, a range of patient and treatment variables were recorded. This analysis included patients who received Combo while in the cohort and were followed; patients were categorized into three groups: continued Combo, switched to TNFi mono, or switched to MTX mono. Baseline was the date of first recorded use of Combo at or following entry to the cohort. Index was the date a patient switched to monotherapy, or for continuing Combo patients, baseline + 24 months (based on average time to switch in monotherapy groups). Predictors of disease activity scores at index were analyzed with ANCOVA.

Results: TNFi + MTX was used by 341 patients, with 46% remaining on Combo and 31% and 23% switching to TNFi mono or MTX mono, respectively. Half (51%) of the switches to monotherapy occurred in the first year after baseline, with an average time to switch of 23.4 months. Patient characteristics at index were significantly different across groups for mean age (older for switch to MTX mono) and biologic initiation era (less in late era for switch to MTX mono); nonsignificant trends were seen for gender and disease status (Table 1). Disease Activity Score 28-joint with C-reactive protein (DAS) at index was predicted by early TNFi initiation era (p=0.0072), longer disease duration (p<0.0001), and higher baseline DAS score (p<0.0001), but not by treatment group (Table 2). Other disease activity measures had similar predictors at index, except Rheumatoid Arthritis Disease Activity Index (RADAI), which was predicted by higher baseline RADAI score (p=0.0004) and marginally by treatment group (p=0.0503) (Table 2).

Conclusion: Over half the patients on Combo transitioned to TNFi mono or MTX mono, a majority during the first year of combo therapy on study. Patients switching to MTX mono were older than patients continuing Combo or switching to TNFi mono, but not much different in disease activity or time on therapy. Disease duration and baseline disease activity had the greatest influence on disease activity at the time of medication change.

Table 1. Demographic and Disease Characteristics at Index (Date of the Switch)

Characteristic at index*

Continued
Combo
TNFi + MTX
(n = 157)

Switched
to TNFi
Mono
(n = 105)

Switched
to MTX
Mono
(n = 79)

p†

Age (years)

61.17 ± 11.83

59.36 ± 15.07

64.9 ± 12.92

0.0256

Female

140 (89.2%)

85 (81.0%)

63 (79.7%)

0.0831

White

144 (87.8%)

99 (90.0%)

76 (88.4%)

0.3099

Disease status by DAS

(n = 123)

(n = 84)

(n = 60)

 

 

Remission (DAS < 1.6)

39 (31.7%)

21 (25.0%)

13 (21.6%)

0.4748‡

 

Low (1.6 ≤ DAS ≤ 2.4)

32 (26.0%)

28 (33.3%)

15 (25.0%)

 

 

Moderate (2.4 < DAS ≤ 3.7)

29 (23.6%)

22 (26.2%)

15 (25.0%)

 

 

High (DAS > 3.7)

23 (18.7%)

13 (15.5%)

17 (28.3%)

 

Biologic initiation era

 

 

 

 

 

Late (2012-2016)

32 (20.4%)

13 (12.4%)

5 (6.3%)

0.0153‡

 

Intermediate (2006-2011)

27 (17.2%)

11 (10.5%)

13 (16.5%)

 

 

Early (2003-2005)

98 (62.4%)

81 (77.1%)

61 (77.2%)

 

Time from baseline to switch, months

–

23.4 ± 24.5

23.5 ± 22.2

0.9357

 

<1 year

–

56 (53.3%)

38 (48.1%)

 

 

1-2 years

–

23 (22.0%)

13 (16.4%)

 

 

2-3 years

–

7 (6.6%)

16 (20.3%)

 

 

3-4 years

–

9 (8.6%)

4 (5.1%)

 

 

>4 years

–

10 (9.5%)

8 (10.1%)

 

Treatment duration, months

 

 

 

 

 

Time on TNFi before index

28.2 ± 20.5

29.7 ± 28.4

24.6 ± 23.2

0.3350

 

Time on MTX before index

34.3 ± 25.0

28.6 ± 27.1

35.2 ± 29.2

0.1541

Data are presented as mean ± SD or n (%)

Abbreviations: DAS, Disease Activity Score 28-joint count with C-reactive Protein; MTX, methotrexate; TNFi, tumor necrosis factor inhibitor

*For each patient who continued combination therapy, the index date was calculated as their baseline date plus 24 months (the average time to switch in the other groups)

†Significant values (p < 0.05) are bolded; p by ANOVA for means (F-tests) and Chi-square for frequency counts

‡P-value across all categories

 

Table 2. Predictors of Disease Activity Scores at Index

 

 

DAS

(N = 251)

RAPID3

(N = 211)

SDAI

(N = 227)

CDAI

(N = 245)

RADAI

(N = 113)

Est*

p*

Est*

p*

Est*

p*

Est*

p*

Est*

p*

Treatment

 

 

 

 

 

 

 

 

 

 

 

Switch to TNFi mono

-0.01

.9741

0.09

.9164

0.11

.9451

0.25

.8697

-0.77

.0503

 

Switch to MTX mono

0.20

.2986

-0.95

.3032

1.99

.2865

2.66

.1218

-0.70

.1479

 

Continued combo

..

 

..

 

..

 

..

 

..

 

Age (per 10y)

0.0008

.8955

0.040

.1913

-0.002

.9772

-0.02

.7715

0.00

.8103

Gender

 

Male

-0.04

.8462

1.01

.3110

-0.80

.6865

0.04

.9831

-0.23

.6231

 

Female

..

..

..

..

..

College graduate

 

Yes

0.09

.5947

0.49

.5184

1.06

.5049

-0.16

.9141

-0.30

.4422

 

No

..

..

..

..

..

Marital status

 

Married

0.09

.5622

-0.50

.5111

0.28

.8574

-2.36

.0930

-0.09

.8068

 

Other

..

..

..

..

..

Biologic era

 

Early†

0.65

.0072

2.10

.0941

6.08

.0112

5.58

.0115

0.65

.1889

 

Intermediate†

0.26

.3528

2.01

.1549

3.30

.2199

1.60

.5137

0.67

.1962

 

Late†

..

..

..

..

..

Disease duration

0.03

<.0001

0.09

.0063

0.30

<.0001

0.30

<.0001

0.03

.1274

Steroid use

 

No

-0.16

.3172

-0.67

.3634

-1.05

.4888

-0.70

.6183

-0.48

.2133

 

Yes

..

..

..

..

..

Narcotic use

 

No

0.47

.1030

-0.01

.9902

5.24

.0707

5.41

.0361

-0.08

.9105

 

Yes

..

..

..

..

..

Baseline score

0.32

<.0001

0.46

<.0001

0.32

<.0001

0.31

<.0001

0.34

.0004

Positive values are higher/worse disease activity, negative values are lower/better disease activity

Abbreviations: CDAI, Clinical Disease Activity Index; DAS, Disease Activity Score 28-joint count with C-reactive protein; MTX, methotrexate; RADAI, Rheumatoid Arthritis Disease Activity Index; RAPID3, Routine Assessment of Patient Data 3; SDAI, Simplified Disease Activity Index; TNFi, tumor necrosis factor inhibitor

*Significant values (p < 0.05) are bolded; estimate (Est) and p by analysis of covariance

†Era of biologic initiation: early (2003-2005), intermediate (2006-2011), or late (2012-2016)

 

Disclosure: N. A. Shadick, Bristol-Myers Squibb, 5,Amgen Inc., 2,Mallinckrodt, 2,UCB, Inc., 2,Crescendo Biosciences, 2,Sanofi, 2,Bristol-Myers Squibb, 2,DxTerity, 2; M. E. Weinblatt, Amgen Inc., 5,Bristol-Myers Squibb, 5,Crescendo Bioscience, 5,UCB, Inc., 5,Amgen Inc., 2,Bristol-Myers Squibb, 2,Crescendo Bioscience, 2,Sanofi/Regeneron, 2; C. K. Iannaccone, None; M. Frits, None; T. Davis, Health Analytics, 3; C. Young, Health Analytics, 3; D. H. Collier, Amgen Inc., 3,Amgen Inc., 1; M. Gharaibeh, Amgen Inc., 3,Amgen Inc., 1; B. S. Stolshek, Amgen Inc., 3,Amgen Inc., 1.

To cite this abstract in AMA style:

Shadick NA, Weinblatt ME, Iannaccone CK, Frits M, Davis T, Young C, Collier DH, Gharaibeh M, Stolshek BS. Characteristics of Patients and Predictors of Composite Disease Activity Scores for Switching to Monotherapy Vs Continuing TNF Inhibitor and Methotrexate Combination Therapy in RA: A Retrospective Analysis of the Brigham and Women’s Rheumatoid Arthritis Sequential Study Registry [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/characteristics-of-patients-and-predictors-of-composite-disease-activity-scores-for-switching-to-monotherapy-vs-continuing-tnf-inhibitor-and-methotrexate-combination-therapy-in-ra-a-retrospective-ana/. Accessed .

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