Clinical and economic analysis of outcomes of dose tapering or withdrawal of tumor necrosis factor-α inhibitors upon achieving stable disease activity in rheumatoid arthritis patients

Figures & data

Figure 1 Markov model structure.

Notes: Patients entering the model in disease control withdraw from all treatment, reduce treatment dose, or maintain treatment. In each monthly cycle, disease control may be lost, at which point they will resume treatment and then potentially regain disease control.
Abbreviations: ADA, adalimumab; DAS28, 28-joint count Disease Activity Score; ETA, etanercept; IFX, infliximab; LDA, low disease activity.

Table 1 Characteristics of studies included within the efficacy meta-analytic regression

Study	Anti-TNF	RA patient type	Model entry criterion	Strategies	Loss of disease control data (follow-up mo: no/total)	Reinduction data (mo: no with control/total)
OPTIMA^Citation13	ADA	Early	DAS28-CRP < 3.2 for 1 mo	Withdrawal Maintain	12: 19/101 12: 9/105	–
Chatzidionysiou et al^Citation14	ADA	Established	DAS28 < 2.6 for ≥ 3 mo	Withdrawal Maintain	7: 10/15 7: 1/16	–
HONOR^Citation15,Citation16	ADA	Established	DAS28 < 2.6 for 6 mo	Withdrawal Maintain	6: 21/50 12: 27/52 12: 4/23	6: 2/6
Tanaka et al^Citation2	ADA	Established	DAS28 < 2.6 for ≥ 6 mo	Withdrawal	6: 13/30, 12: 6/16	–
PRESERVE^Citation17	ETA	Established	DAS28 < 3.2 at a single time-point	Withdrawal Taper Maintain	12: 113/197 12: 42/201 12: 35/201	–
PRIZE^Citation18	ETA	Early	DAS28 < 2.6 at 12 mo	Withdrawal Withdrawala Taper	9: 50/65 9: 40/65 9: 23/63	–
DOSERA^Citation19	ETA	Established	DAS28 ≤ 3.2 for ≥ 11 mo	Withdrawal Taper Maintain	12: 20/23 12: 15/27 12: 11/23	24: 19/20 24: 13/15 24: 10/11
ENCOURAGE^Citation20	ETA	Early	DAS28 < 2.6 for 6 mo	Withdrawal Maintain	6: 10/28, 12: 13/28 6: 3/32, 12: 4/32	–
CORRONA^Citation21	ETA	Established	DAS28 < 2.6 DAS28 < 2.6 DAS28 < 3.2 DAS28 < 3.2	Taper Maintain Taper Maintain	6: 7/44, 12: 22/39 6: 42/218, 12: 89/186 6: 11/88, 12: 45/76 6: 59/519, 12: 133/418	–
Campbell et al^Citation22	ETA	Established	DAS28 < 3.2b	Taper	6: 6/15	–
Kamiya et al^Citation23	ETA	Established	DAS28 < 2.6 for ≥ 6 mo	Withdrawal	6: 13/20	–
Urata et al^Citation24	ETA	Established	DAS28 < 2.6 (duration unknown)	Withdrawal	24: 14/23	–
RRR^Citation25	IFX	Established	DAS28 < 3.2 for 24 wk	Withdrawal	12: 46/102	–
Brocq^Citation26	ADA, ETA, IFX	Established	DAS28 < 2.6 for ≥ 6 mo	Withdrawal	Individual patient data (n = 13)	Individual patient data (n = 10)

Notes:

a Patients continued with methotrexate therapy, but not anti-TNF.

b On 2 assessments at least 1 mo apart.

Abbreviations: ADA, adalimumab; anti-TNF, tumor necrosis factor-α inhibitor; CRP, C-reactive protein; DAS28, 28-joint count Disease Activity Score; ETA, etanercept; IFX, infliximab; mo, month(s); RA, rheumatoid arthritis; wk, weeks.

Figure 2 Mean number of months until loss of disease control for each drug and treatment strategy.

Abbreviations: ADA, adalimumab; DAS, Disease Activity Score; ETA, etanercept; IFX, infliximab; LDA, low disease activity; RA, rheumatoid arthritis.

Table 2 Meta-analysis results estimating the risk of flare

Covariate	Hazard ratio	95% credible intervala
Strategy
Withdrawal	Referenceb
Tapering	0.45	0.36–0.54
Maintenance	0.33	0.28–0.38
RA patient type
Early	Reference
Established	1.77	1.53–2.03
Model entry criterion
DAS28 < 3.2	Reference
DAS28 < 2.6	1.47	1.21–1.77
Treatment
ADA	Reference
ETA	2.07	1.67–2.55
IFX	1.31	0.89–1.85

Notes: The analysis is adjusted for treatment strategy, anti-TNF, and RA patient type, and model entry criterion.

a Credible intervals represent the range in which the estimate will fall with 95% probability. Estimates with credible intervals not including 1 are considered to be statistically significant.

b Reference hazard = 0.025.

Abbreviations: ADA, adalimumab; anti-TNF, tumor necrosis factor-α inhibitor; DAS28, 28-joint count Disease Activity Score; ETA, etanercept; IFX, infliximab; RA, rheumatoid arthritis.

Figure 3 Total 5-year direct costs of withdrawal, tapering, and maintenance after a period of sustained remission or LDA.

Notes: Black and white portions of bars indicate mean medical and anti-TNF costs, respectively (left axis). Values within each bar indicate total costs (top, in thousands of Euros) and the proportion of costs due to anti-TNFs (bottom, in %).
Abbreviations: ADA, adalimumab; anti-TNF, tumor necrosis factor-α inhibitor; ETA, etanercept; IFX, infliximab; LDA, low disease activity; RA, rheumatoid arthritis.

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