Predictors of Long Term Survival of Low-Dose Etanercept: An Observational Study

Francesca Ometto¹, Bernd Raffeiner^2,3, Costantino Botsios², Davide Astorri⁴, Lara Friso², Livio Bernardi⁵, Leonardo Punzi⁶ and Andrea Doria², ¹Rheumatology Unit, Department of Medicine - DIMED, University of Padova, PADOVA, Italy, ²Rheumatology Unit, Department of Medicine - DIMED, University of Padova, Padova, Italy, ³Rheumatology Unit, Internal Medicine, General Hospital of Bolzano, Bolzano, Italy, ⁴Rheumatology Unit, Department of Medicine - DIMED, University of Padova, padova, Italy, ⁵Rheumatology Unit, Department of Medicine -DIMED, University of Padova, PADOVA, Italy, ⁶Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Biologic drugs, etanercept, remission, rheumatoid arthritis (RA) and treatment options

Session Information

Date: Tuesday, November 15, 2016

Title: Rheumatoid Arthritis – Clinical Aspects - Poster III: Treatment – Monitoring, Outcomes, Adverse Events

Session Type: ACR Poster Session C

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

Background/Purpose: The objective of the study was to investigate long-term survival of low-dose etanercept (ETN) (25 mg weekly) and possible predictors of survival.

Methods: We collected retrospectively data of RA patients starting full-dose ETN (25 mg twice a week) between April 2001 and September 2014 who tapered ETN and maintained low-dose ETN for at least 12 months. Patients were evaluated every 3 months with a treat-to-target approach. Patients who achieved and maintained remission (DAS28 <2.6) for at least 6 months with full-dose ETN, tapered ETN. If remission was lost in two consecutive visits the patient returned to full-dose. We recorded the time to achieve remission with full-dose ETN (TTR). We considered two different cut-offs of TTR: <=6 months and <=12 months. We then evaluated survival of low-dose ETN treatment and possible predictors. Variables collected are reported in Table I. Survival was analysed with Cox-regression. Covariates included were those achieving a p<0.20 in univariate analysis. A separate Cox regression analysis was run with TTR<=6 months and TTR<=12 months.

Results: Among 532 patients, 276 were excluded because of missing data or because they were lost to follow-up leaving 256 patients eligible. After 11.28±4.05 years, 50/256 (19.5%) returned to full dose because of disease relapse, 55/256 (21.5%) stopped the treatment with ETN, and 151/256 (59.0%) maintained low-dose. TTR<=6 months and TTR<=12 months resulted significant predictors of low-dose survival (OR 1.93, 95% C.I. 1.31-2.85, p=0.001 and OR 3.11, 95% C.I. 2.06-4.68; p<0.001, respectively) together with a lower mean prednisone daily dose (Table II, Figure 1).

Conclusion: A shorter TTR and a lower mean prednisone daily dose are predictors of long-term survival of low-dose ETN. TTR<=6 months and TTR<=12 months are associated with a 2-fold and 3-fold increased probability of low-dose ETN survival respectively.

Table I. Characteristics of the patents according to the maintenance of half-dose etanercept.
		Univariate Analysis
	All patients	Low-dose survival	Low-dose failure	p value
Number	256	151	105
Patients who stopped etanercept t, n (%)	55 (21.5)	–	55 (52.4)	–
Patients who returned to full-dose etanercept, n (%)	50 (19.5)	–	50 (47.6)	–
Age, median (IQR), years	59.00 (49.00;67.00)	60.00 (50.00;68.00)	58.00 (47.00;66.50)	0.266
Females, n (%)	217 (84.8)	126 (83.4)	91 (86.7)	0.301
Positive RF orACPA, n (%)	164 (64.6)	101 (67.3)	63 (60.6)	0.165
Disease duration, median (IQR), years	15.00 (9.25;21.00)	14.00 (9.00;21.00)	15.00 (10.00;22.00)	0.510
Etanercept treatment duration, median (IQR), years	8.00 (5.00;10.00)	8.00 (5.00;10.00)	7.00 (5.00;10.00)	0.177
Low-dose etanercept treatment duration, median (IQR), years	4.00 (1.27;8.00)	7.00 (4.00;9.00)	1.75 (0.58;3.00)	<0.001
Mean prednisone daily dose, median (IQR), mg	2.50 (0.00;5.00)	2.50 (0.00;5.00)	5.00 (2.50;5.00)	0.011
Combination with methotrexate or leflunomide, n (%)	129 (50.4)	78 (51.7)	51 (48.6)	0.360
Baseline DAS28, median (IQR)	5.17 (4.50;5.53)	5.20 (4.48;5.47)	5.08 (4.68;5.65)	0.646
Baseline C-reactive protein, median (IQR), mg/L	12.00 (6.00;25.00)	12.00 (6.00;22.00)	12.65 (5.00;31.50)	0.491
Time to remission, median (IQR), years	0.50 (0.08;1.56)	0.25 (0.08;0.83)	1.17 (0.08;2.88)	<0.001
Time to remission <=6 months, n (%)	167 (65.2)	110 (72.8)	57 (52.3)	0.002
Time to remission <=12 months, n (%)	200 (78.1)	134 (88.7)	66 (62.9)	<0.001

Table II. Survival of low-dose etanercept according to time to remission: results of Cox regression analysis.
		Model I		Model II
		Time to remission ² 6 months		Time to remission ² 12 months
		OR (95% CI)	p value	OR (95% CI)	p value
Positive RF or ACPA		0.84 (0.56;1.25)	0.382	0.92 (0.62;1.37)	0.677
Mean prednisone daily dose	per milligram increase	1.13 (1.04;1.23)	0.004	1.12 (1.03;1.21)	0.010
Time to remission <=6 months		1.93 (1.31;2.85)	0.001	–	–
Time to remission <=12 months		–	–	3.11 (2.06;4.68)	<0.001

Figure 1. Low-dose etanercept survival according to time to remission.

Disclosure: F. Ometto, None; B. Raffeiner, None; C. Botsios, None; D. Astorri, None; L. Friso, None; L. Bernardi, None; L. Punzi, None; A. Doria, None.

To cite this abstract in AMA style:

Ometto F, Raffeiner B, Botsios C, Astorri D, Friso L, Bernardi L, Punzi L, Doria A. Predictors of Long Term Survival of Low-Dose Etanercept: An Observational Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/predictors-of-long-term-survival-of-low-dose-etanercept-an-observational-study/. Accessed .

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