Session Information
Date: Sunday, October 21, 2018
Session Title: Rheumatoid Arthritis – Treatments Poster I: Strategy and Epidemiology
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
Co-medication with conventional synthetic DMARDs (csDMARDs) is currently recommended with all targeted therapies (bDMARDs and tsDMARDs) for the management of rheumatoid arthritis (RA). However, targeted DMARDs are often used as monotherapy,
primarily because of intolerance to methotrexate and other csDMARDs. Our aim was to analyze the impact of comedication with csDMARDs on the effectiveness of tofacitinib (TOFA), Tumor Necrosis Factor inhibitors (TNFi) and biologic agents with an alternative mode of action (OMA, abatacept or tocilizumab) in a large cohort of patients with RA.
Methods:
In an observational cohort study (SCQM), we included all RA patients initiating a new therapy with TOFA, TNFi, or OMA between August 2013 and March 2018, who had at least one follow-up visit. We analyzed whether the effectiveness of TOFA, TNFi and OMA was modified by concomitant csDMARDs therapy at baseline (COMBI) compared to monotherapy (MONO). The primary outcome was drug maintenance, defined as the time from initiation to discontinuation of treatment. A secondary outcome was low disease activity (LDA) state based on the CDAI at 12 months.
We used Kaplan Meier curves to display drug maintenance and Cox proportional hazard models to analyze the hazard for treatment discontinuation. We adjusted for potential confounders (gender, age, disease duration, seropositivity, BMI, smoking, baseline CDAI number of distinct previous bDMARDs). We applied multiple imputation to account for missing baseline covariate data.
Results:
A total of 2503 treatment courses were included, 436 on TOFA, 1244 on TNFi, and 823 on OMA. On average, patients on TNFi were younger, less prior bDMARD and received more COMBI. MTX was by far the most commonly prescribed COMBI with all three targeted therapies (88%-90%).(Table)
In multivariable adjusted models, TOFA maintenance was not different in MONO- compared to COMBI-therapy (Hazard Ratio (HR)-MONO: 1.05 (95%CI: 0.77 – 1.45)), nor was OMA maintenance (HR-MONO: 1.04 (95%CI: 0.84 – 1.30)). On the contrary, TNFi maintenance was significantly decreased in MONO (HR-MONO: 1.28 (95%CI: 1.07 – 1.53)).
Low disease activity (LDA) at 12 months was achieved in 47%, 44% and 40% of patients treated respectively with TOFA, OMA or TNFi. The likelihood of reaching LDA with TOFA or with OMA was not significantly modified by MONO (OR-MONO: 1.13 (95%CI: 0.70 – 1.83), OR-MONO: 1.04 (95%CI: 0.84 – 1.30), respectively), while the likelihood of LDA was significantly reduced for TNFi in MONO (OR-MONO: 0.66 (95% CI: 0.49 – 0.89)).
Conclusion:
In this ‘real world’ cohort, combination therapy with csDMARDs did not improve drug-maintenance and effectiveness of TOFA or OMA, whereas TNFi appeared to require comedication for optimal treatment results. Our results suggest that usefulness of concomitant csDMARDs varies according to the type of targeted therapy.
Table – Patient and disease characteristics at treatment initiation
|
|
TOFA |
TNFi |
OMA |
p value |
|
Female sex [%] |
80 |
75 |
76 |
NS |
|
Age [yrs] |
59 |
54 |
59 |
< 0.001 |
|
Tobacco Smoking ever [%] |
31 |
30 |
27 |
NS |
|
BMI [kg/m2] |
26.5 |
26 |
26.3 |
NS |
|
Seropositivity [%] |
69 |
66 |
75 |
< 0.001 |
|
Disease duration [yrs] |
12 |
9 |
11 |
< 0.001 |
|
CDAI (bl) |
22 |
21 |
21 |
NS |
|
Concomitant csDMARDs (@ bl) – None [%] (= MONO) – Including MTX [%] – Other csDMARDs [%] |
45 49 6 |
29 64 7 |
40 53 7 |
<0.001 |
|
Concomitant csDMARDs (@ 1 yr) – None [%] (= MONO) – Including MTX [%] – Other csDMARDs [%] |
49 42 9 |
29 64 7 |
44 49 6 |
<0.001 |
|
Prior bDMARD use – None [%] (= Bio-naive) – 1 prior bDMARD [%] – ≥ 2 prior bDMARDs [%] |
33 26 41 |
60 25 15 |
38 32 30 |
<0.001 |
To cite this abstract in AMA style:
Finckh A, Tellenbach C, Scherer A, Moeller B, Ciurea A, von Mühlenen I, Gabay C, Kyburz D, Mueller R, Hasler P, Zufferey P. The Impact of Comedication with Conventional Synthetic Dmards on Drug Retention and Clinical Effectiveness of Tofacitinib, Anti–Tumor Necrosis Factor Therapy and Biologics with an Alternative Mode of Action in Patients with Rheumatoid Arthritis. a Cohort Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/the-impact-of-comedication-with-conventional-synthetic-dmards-on-drug-retention-and-clinical-effectiveness-of-tofacitinib-anti-tumor-necrosis-factor-therapy-and-biologics-with-an-alternative/. Accessed July 5, 2020.« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-impact-of-comedication-with-conventional-synthetic-dmards-on-drug-retention-and-clinical-effectiveness-of-tofacitinib-anti-tumor-necrosis-factor-therapy-and-biologics-with-an-alternative/