Background/Purpose: Tofacitinib is a novel, oral Janus kinase inhibitor investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis (RA). The efficacy and safety of tofacitinib over 6 months (Mo) in RA patients (pts) with an inadequate response (IR) to TNF inhibitors (TNFi) was reported previously.¹ This is an analysis of TNFi IR populations pooled across Phase 2, Phase 3, and open-label long-term extension (LTE) RA studies providing additional longer-term data and effects of tofacitinib by number of prior failed TNFi.

Methods: Demographic and baseline disease characteristics of TNFi IR pts in Phase 2, Phase 3, and LTE studies were similar, which supports the pooling of these data. ACR20 responses and mean change in HAQ-DI were assessed at 3 Mo in pooled data from pts receiving tofacitinib 5 or 10 mg twice daily (BID) or placebo in 9 randomized Phase 2 and 3 studies ≥3 Mo in duration (monotherapy: NCT00550446, NCT00687193, NCT00814307; background DMARD: NCT00413660, NCT00603512, NCT00960440, NCT00847613, NCT00856544, NCT00853385). Data are reported by number of prior failed TNFi. Long-term efficacy in reducing signs and symptoms (ACR20/50/70, DAS28-4(ESR), DAS28-4[ESR] ≤3.2 and <2.6) and improving physical function (HAQ-DI) over 24 Mo was assessed in pooled data from 2 LTE studies (NCT00413699, NCT00661661).

Results: In an analysis of 614 Phase 2 and Phase 3 pts, tofacitinib demonstrated consistent efficacy in reducing signs and symptoms of RA and improving physical function, as measured by ACR20 and HAQ-DI, respectively, compared with placebo, with similar response irrespective of IR to 1 or 2 prior TNFi (Table 1). Tofacitinib also demonstrated sustained improvements in signs and symptoms and physical function over 24 Mo in LTE, as measured by ACR20/50/70 and DAS-assessments and HAQ-DI, respectively (510 pts included in the analysis) (Table 2).

Conclusion:  Tofacitinib was efficacious regardless of inadequate response to 1 or 2 prior TNFi in improving signs and symptoms of RA and physical function in TNFi IR pts pooled across the RA clinical development program with maintained response demonstrated over 24 Mo in LTE.

¹Burmester et al. Arthritis Rheum 2011;63(Suppl 10):S279

Table 1	Phase 2 and Phase 3
Efficacy (Month 3)	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
% (n/N); p-value vs placebo	ACR20 (%)
All	43.7 (97/222); p<0.0001	50.0 (108/216); p<0.0001	24.0 (41/171)
1 failed TNFi	46.2 (67/145); p<0.01	50.0 (77/154); p=0.0001	27.4 (31/113)
2 failed TNFi	40.6 (26/64); p<0.01	53.1 (26/49); p<0.0001	15.6 (7/45)
≥3 failed TNFi	30.8 (4/13); NS	38.5 (5/13); NS	23.1 (3/13)
	Mean change HAQ-DI (N); p-value vs placebo
All	-0.30 (203); p<0.0001	-0.42 (198); p<0.0001	-0.08 (150)
1 failed TNFi	-0.30 (133); p<0.001	-0.46 (142); p<0.0001	-0.09 (99)
2 failed TNFi	-0.39 (58); p<0.01	-0.41 (44); p<0.01	-0.10 (39)
≥3 failed TNFi	-0.18 (12); NS	-0.06 (12); NS	0.04 (12)
NS, not significant

 

Table 2	LTE
Efficacy	Tofacitinib all (Month 1)	Tofacitinib all (Month 24)
ACR20, % (n/N)	70.1 (354/505)	74.6 (50/67)
ACR50, % (n/N)	46.5 (235/505)	49.3 (33/67)
ACR70, % (n/N)	24.0 (121/505)	32.8 (22/67)
Mean change HAQ-DI (N)	-0.51 (490)	-0.67 (64)
Mean change DAS28-4(ESR) (N)	-2.43 (472)	-2.58 (61)
DAS28-4(ESR) ≤3.2, % (n/N)	34.4 (168/488)	32.8 (22/67)
DAS28-4(ESR) <2.6, % (n/N)	18.9 (92/488)	17.9 (12/67)

 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/short-and-long-term-efficacy-of-tofacitinib-an-oral-janus-kinase-inhibitor-in-the-treatment-of-patients-with-rheumatoid-arthritis-and-an-inadequate-response-to-tnf-inhibitors-analyses-of-pooled-ph/