Approaches and outcomes of adalimumab discontinuation in patients with well-controlled inflammatory arthritis: a systematic search and review

Balay-Dustrude, Erin; Fennell, Jessica; Baszis, Kevin; Goh, Y. Ingrid; Horton, Daniel B.; Lee, Tzielan; Rotman, Chloe; Sutton, Anna; Twilt, Marinka; Halyabar, Olha

doi:10.1186/s12969-024-01046-3

Pediatric Rheumatology

Table 1 Adult rheumatoid arthritis randomized controlled trial literature evaluating Adalimumab discontinuation, flare rates, recapture method and success rates

From: Approaches and outcomes of adalimumab discontinuation in patients with well-controlled inflammatory arthritis: a systematic search and review

First Author	Tascilar	VanMulligen	Emery	Bouman
Year	2021	2020	2020	2017
Study Design	RCT	RCT	RCT	RCT
Trial Name	(RETRO)	(TARA 2Y)	(PREDICTRA)	(DRESS 3Y)
Sites	14	12	54	2
Enrolled (N)	299	189	122	180
ADA specific taper^a	24 (13%)	40 (42%)	122 100%	42 (35%)
Tapering method	Dose reduction and abrupt stop	Dose reduction and prolonged dosing interval	Abrupt stop and prolonged dosing interval	Prolonged dosing interval
Population RF/CCP prevalence	RF 57% CCP 56%	RF 58% CCP 68%	NA	RF 80% CCP 73%
Study Duration (months)	12	24	9	36
CID/LDA definition	DAS28-ESR < 2.6 for 6 months	DAS ≤ 2.4 and SJC ≤ 1 at 2 time points within 3 months	DAS28-ESR/CRP < 2.6 for ≥ 6 months and DAS28-ESR < 2.6 at screening	LDA at 2 visits, determined by rheumatologist and DAS28-CRP
Patient reported assessments	PtGA, HAQ	HAQ-DI, SF-36, EQ-5D	HAQ-DI, PtGA, Rapid-3, SF-36, FACIT-fatigue	HAQ-QI, EQ5D
Background therapy	NA	100% csDMARDs in TNFi taper group	80% MTX	50% MTX
Flare Rates	Taper:43% (40/93)	TNFi 1st: 62%	Taper:36% (37/102)	Taper:
	Abrupt stop:55% (53/96)	csDMARD 1st: 61%	Abrupt stop:45% (9/20)	Major flare:17% (20/115)
	Continue:16/93 (17%)	(p = 0.84)		Minor flare:83% (96/115)
	No ADA specific data			Continue:14% (8/57)
Recapture method	Restart previous medication	Restart previous medication	ADA standard dosing	Restart previous medication
Recapture results	Taper: 62% (21/34)	46% at wk 12	38% (15/37) by wk 16	NA
	Abrupt stop: 76% (35/46)	67% at wk 24	Taper: 38% (11/29)
			Abrupt stop: 50% (4/8)
Factors associated with successful discontinuation	Autoantibody negativity, male gender, shorter disease duration, lower baseline DAS28	NA	Deep remission prior to medication discontinuation	NA
Evidence quality	1	1	1	1
First Author	El Miedany	Fautrel	Chatzidionysiou	Smolen
Year	2016	2016	2016	2014
Study Design	RCT	RCT	RCT	RCT
Trial Name	NA	(STRASS)	(ADMIRE)	(OPTIMA)
Sites	1	23	8	161
Enrolled (N)	157	138	31	207
ADA specific taper^a	46 (37%)	29 (45%)	15 (100%)	102 (100%)
Tapering method	Abrupt stop and prolonged dosing interval	Prolonged dosing interval	Abrupt stop	Abrupt stop
Population RF/CCP prevalence	RF 50% CCP 60%	RF 68% CCP 80%	RF 58% CCP 66%	RF 95% CCP 90%
Study Duration (months)	12	18	12	12
CID/LDA definition	DAS28 < 2.6-ESR for 6 months, 3 visits	DAS28 < 2.6 for ≥ 6 months	DAS < 2.6 for 3 months at baseline and one more occasion 3–6 months prior	Stable LDA: DAS28-CRP < 3.2 at 22 or 26 weeks of treatment
Patient reported assessments	PROMS questionnaire	HAQ score	HAQ score	PtGA, Patient pain VAS, HAQ-DI
Background therapy	79% MTX	75% MTX or leflunomide	100% MTX	100% MTX
	21% other csDMARDs
Flare Rates	Overall: 62% (77/125)	Taper:77% (49/64)	Abrupt stop:87% (13/15)	Abrupt stop: -DAS28 > 2.6: 33% (34/101) -DAS28 > 3.2: 18% (19/101)
	Tapered: 51% (32/63)	Continue:47% (34/74)	Continue:19% (3/16)	Continue: -DAS28 > 2.6: 14% (15/105) -DAS28 > 3.2: 8.5% (9/105)
	Abrupt stop: 73% (45/62)	(p = 0.0004)
	Continue: 6.5% (2/32)
Recapture method	Restart previous medication	Restart previous medication	ADA standard dosing	ADA standard dosing
Recapture results	100% (77/77) by week 16	41% (20/49) CID	90% (8/9) wk 12	NA
		39% (19/49) LDA	100% (9/9) wk 52^a
		8% (4/49) Moderate DA
Factors associated with successful discontinuation	Lower DAS-28 score and better remission quality, Anti-CCP negativity, improving functional disability over 12 weeks, lower ultrasound greyscale and power doppler scores at 12 weeks	Spacing strategy, baseline HAQ score, RF negativity	Shorter disease duration, earlier ADA treatment start,, lower baseline DAS28 score	NA
Evidence quality	1	2	2	1

After data extraction, a study by Bouman et al. replaced Van Herwaarden et al., as both studies were from the DRESS trial, and Bouman reported longer follow up time
RCT randomized controlled trial, ADA Adalimumab, CCP cyclic citrullinated protein, RF Rheumatoid Factor, TNFi TNF inhibitor, MTX methotrexate, csDMARD conventional synthetic disease modifying antirheumatic drug, VAS visual analog scale, PtGA patient global assessment, NA not available, Wk week, CID clinically inactive disease, LDA low disease activity, DA disease activity, SF-36 short form-36, SJC swollen joint count, EQ5D European Quality of Life-5 Dimensions, HAQ-DI Health Assessment Questionnaire
Disability Index. CRP C-reactive protein, ESR erythrocyte sedimentation rate
Recapture results reflect reported information only
Evidence quality was determined using the Oxford Centre for Evidence-Based Medicine: levels of Evidence (2009) guidance
^aADA specific indicates the number of patients who specifically tapered adalimumab

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ISSN: 1546-0096

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