Subcutaneous abatacept for the treatment of rheumatoid arthritis

Abstract

The efficacy, safety and tolerability of i.v. abatacept are well established in patients with active RA. A s.c. abatacept formulation is now available in some countries. Here, we review clinical data for s.c. abatacept. Six trials are presented (Phase II dose-finding study, ACQUIRE, ALLOW, ACCOMPANY, ATTUNE and AMPLE) and issues important to both patients and clinicians are addressed. The primary focus assesses whether the i.v. and s.c. abatacept formulations have similar efficacy, including whether the recommended fixed dose of s.c. abatacept is comparable to the weight-tiered i.v. dosing and whether efficacy is sustained with long-term treatment. Safety and immunogenicity are also discussed, including the short- and long-term safety of s.c. abatacept, and whether immunogenicity is increased following a switch from i.v. to s.c. abatacept, after withdrawal or reintroduction of s.c. abatacept or in the absence of MTX. Year 1 data from the AMPLE study, comparing s.c. abatacept with the TNF antagonist adalimumab, are discussed. Although fewer patient-years of exposure are available for s.c. compared with i.v. abatacept, observations suggest that s.c. abatacept has a similar long-term efficacy to the i.v. formulation, improving the signs, symptoms, disease activity and physical function in patients with RA. With continued treatment, these improvements are maintained over time with high retention rates, similar to i.v. abatacept. s.c. abatacept is associated with low immunogenicity and short- and long-term safety that is consistent with i.v. abatacept. In addition, s.c. abatacept demonstrates comparable efficacy, kinetics of response, safety and radiographic inhibition to adalimumab.

Keywords: abatacept; biologic therapy; rheumatoid arthritis; subcutaneous.

Figures

Fig. 1

Proportion of s.c. or i.v. abatacept-treated patients in the ACQUIRE study achieving ACR20, -50 or -70 responses (A) over 6 months for the per protocol (PP) population (n = 693 in the s.c. abatacept-treated group, n = 678 in the i.v. abatacept-treated group; non-responder analysis) [11] and (B) over 32 months for patients who entered the LTE (all patients received s.c. abatacept + MTX, n = 1372; as-observed analysis) [26]. Fig. 1b Copyright © 2011 by the American College of Rheumatology. Fig. 1b Copyright © 2012 by the American College of Rheumatology. The ACQUIRE study compared s.c. vs i.v. abatacept in MTX-IR patients. (A) The estimated difference between the s.c. and i.v. treatment groups for ACR20 at month 6 in the PP population (primary endpoint) was 0.3% (95% CI −4.2, 4.8). (B) Not all patients reached later time points at the time of data analysis. Data on eight patients were excluded from all efficacy analyses due to site non-compliance with study procedures. Error bars represent 95% CI.

Fig. 2

Mean change from baseline DAS28 (CRP) score in patients in the ACCOMPANY study (A) over 4 months for the ITT population [n = 49 in the s.c. abatacept monotherapy group, n = 51 in the s.c. abatacept combination (plus MTX) group] and (B) over 18 months for patients who entered the LTE (n = 43 in the monotherapy group, n = 47 in the combination group) (as-observed analysis). [15]. Copyright © 2012 by the American College of Rheumatology. The ACCOMPANY study compared s.c. abatacept with or without MTX in patients with an inadequate response to ≥1 DMARD (MTX-naïve or MTX-IR). Mean (s.d.) baseline DAS28 (CRP) was 5.4 (1.4). Error bars represent 95% CI.

Fig. 3

The proportions of patients in the AMPLE study meeting ACR20, -50, and -70 responses over 1 year for the ITT population (n = 318 in the s.c. abatacept group, n = 328 in the adalimumab group). [19]. Copyright © 2013 by the American College of Rheumatology. AMPLE is an ongoing study comparing s.c. abatacept vs adalimumab in biologic-naïve patients with background MTX. Error bars represent 95% CI.

Fig. 4

Cumulative probability plot showing the distribution of change in van der Heijde modified total Sharp scores from baseline to year 1 for patients in the AMPLE study. [19]. Copyright © 2013 by the American College of Rheumatology. AMPLE is an ongoing study comparing s.c. abatacept vs adalimumab in biologic-naïve patients with background MTX. Paired (baseline and year 1) radiographic images were available for 91.1% of patients in the abatacept group and 88.1% of patients in the adalimumab group.