Background/Purpose: EULAR recommendations advocate Methotrexate (MTX) as first line therapy. For patients (pts) who fail to attain remission or low disease activity (LDA) after 6 months of MTX treatment, TNF inhibitors should be added to the therapeutic regimen in pts with high risk of bad outcome. This post hocanalysis examined outcomes following open label (OL) adalimumab (ADA) +MTX in rheumatoid arthritis (RA) pts who did not achieve a stable LDA target at 22 and 26 weeks (wks) either from ADA+MTX or MTX monotherapy. Consequences of optimizing or not optimizing therapy were assessed.

Methods: OPTIMA was a 78 wk, randomized, double-blind, double-treatment period study designed to compare safety and efficacy of ADA+MTX with placebo (PBO) +MTX in early RA pts. Following ADA+MTX or PBO+MTX treatment for 26 wks (Period 1), non-responders (NR) were defined as pts failing to achieve a stable LDA target of DAS28(CRP) <3.2 at wks 22 and 26 and given OL ADA+MTX for an additional 52 wks, (Period 2) (OL ADA Carry On and Rescue ADA arms, respectively). Period 2 responders were defined as those achieving LDA at wk78 following OL ADA+MTX therapy. Logistic regression analysis was conducted with baseline and wk26 disease characteristics as variables.

Results: Compared with responders, Period 1 NR began the study with higher overall disease activity. Among these, 78/259 (30%) OL ADA Carry On and 157/348 (45%) Rescue ADA pts achieved DAS28(CRP) <3.2 following 26 wks of OL ADA+MTX therapy; 33/259 (13%) and 49/348 (14%) OL ADA Carry On and Rescue ADA pts, respectively, had DAS28(CRP) ≥3.2 at wk52 and achieved DAS28(CRP) <3.2 at wk78. Mean values of responders’ clinical, radiographic, and functional outcomes were much lower than those of NR and were similar to those seen for pts who achieved the treatment target within the first period. This indicates that starting with MTX followed by ADA in insufficient responders to MTX is an appropriate strategy; a small subset of pts responds more slowly to MTX/ADA combination from start (Table). ACR20/50/70 scores for the Rescue ADA arm from wk26 to wk78 were sizeable (51%, 34%, and 19%, respectively). OL ADA Carry On arm achieved ACR20/50/70 from wk26 baseline in 27%, 15%, and 8% of pts, respectively, at wk78. Age, patient and physician’s global assessment of disease, and tender/swollen joint counts were all predictors of achieving DAS28(CRP) <3.2 at wk78.

 

Table. Period 2 Responder vs. Non-Responder Outcomes
	DAS28(CRP)				mTSS				HAQ-DI
	Responders		Non-Responders		Responders		Non-Responders		Responders		Non-Responders
	COa	RESb	COa	RESb	COa	RESb	COa	RESb	COa	RESb	COa	RESb
	n=106	n=175	n=121	n=142	n=106	n=175	n=120	n=142	n=106	n=175	n=121	n=142
Baseline	6.13c	5.98d	6.32e	6.34f	10.16c	11.15	11.98	13.44	1.75c	1.59g	1.71	1.73
Week 26	3.73	4.13	4.41	4.88	10.34	12.75	12.27	14.14	0.82	0.94	1.10	1.20
Week 52	2.38	2.29	4.34	4.25	10.38	12.76	12.32	14.18	0.62	0.53	1.10	1.02
Week 78	2.71	2.28	4.02	3.81	10.66	12.65	12.41	14.51	0.60	0.50	1.08	1.01
aADA Carry On arm; bRescue ADA arm; cn=105; dn=169; en=118; fn=141; gn=174; DAS28(CRP), 28-joint disease activity score with C-reactive protein; mTSS, modified total Sharp score; HAQ-DI, disability index of the health assessment questionnaire.

Conclusion: When advanced to OL ADA+MTX therapy, pts initially not achieving stable LDA target at wk26 following MTX monotherapy demonstrated improvements in clinical and functional outcomes at wk52 and wk78. In addition, structural progression was minimal. Some improvement was also seen among pts who did not yet attain stable LDA at wk26 on ADA+MTX but continued this treatment; however, it remains unknown whether pts who were not in LDA at wk78 might have benefited from earlier treatment adjustment in an attempt to further improve outcomes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-adalimumab-plus-methotrexate-therapy-in-rheumatoid-arthritis-non-responders-receiving-methotrexate-monotherapy-or-adalimumab-combination-therapy-results-from-the-optima-trial/