Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial

Genovese, Mark C.; Pacheco‐Tena, César; Covarrubias, A.; Léon, G.; Mysler, Eduardo; Keiserman, Mauro Waldemar; Valente, R.; Nash, Peter; Campos, Jesus Abraham Simón; Box, Jane; Legerton, Clarence W.; Nasonov, E.; Durez, Patrick; Elegbe, A.; Wong, Robert; Li, Xiaohui; Banerjee, Subhashis; Alten, Rieke

doi:10.3899/jrheum.170344

Cited by 29 publications

(17 citation statements)

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“…An integrated analysis of safety data from the double-blind and open-label periods of 5 clinical trials including a total of 1879 RA refractory patients with 4214.6 patient-years of exposure, showed that treatment with SC ABA was associated with a low incidence of serious infections, malignancies, autoimmune events, and injection-site reactions [ 39 ]. Our data regarding the safety profile of SC ABA are similar to the 5-year extension period of the ACQUIRE study [ 40 ], and RWD from the ACTION study [ 13 ]. In addition, similar results have been found in Argentine patients with respect to the security profile when exposed to IV ABA administration [ 20 ].…”

Section: Discussionmentioning

confidence: 62%

Subcutaneous abatacept in rheumatoid arthritis: A real-life experience

Sarmiento-Monroy

Parada-Arias

Rodríguez-López

et al. 2019

Journal of Translational Autoimmunity

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Objectives To assess the effectiveness, safety, and drug survival of subcutaneous (SC) abatacept (ABA) in a cohort of rheumatoid arthritis (RA) patients in a real-world setting. Methods This was a retrospective cohort study from 2014 to 2018 in which patients with RA (1987 ACR criteria) were included. Patients were evaluated at a single rheumatology outpatient center in Bogotá, Colombia. The patients were classified according to their treatment background: biological-naïve (n = 65), switched from IV to SC ABA administration (125 mg-wk) (n = 32), and inadequate response to biological DMARD (n = 62). The primary endpoint was a change in DAS28-CRP and RAPID3 from baseline to 12 months. A linear mixed effect model was used to correlate repeated measures. Adverse events were assessed and recorded during each visit to the rheumatology center. Several Cox proportional hazard regression models were used to test if there were any differences in drug survival curves based on seropositivity for rheumatoid factor (RF), and anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP). Statistical analysis was done using software R version 3.4.4. Results A total of 159 patients were included. Baseline characteristics of patients were as follows: female gender 84%, median age of 54 years (IQR 16), median disease duration 10 years (11), RF positive 96%, anti-CCP positive 89%, erosive disease 55%, median DAS28-CRP 5.0 (2), and median RAPID3 17 (10). Concomitant use of methotrexate and SC ABA monotherapy were reported at 52% and 30% respectively. Demographics and disease characteristics were similar for all groups, except for baseline DAS28-CRP, and RAPID3 in the group that switched route of administration. The interaction between time and group was significant (p = 0.0073) for RAPID3. Infections, constitutional symptoms, and headaches were the most frequent AEs. Retention rate corresponded to 60% at 48 months. The most frequent reason for drug suspension was loss of efficacy. Median time of treatment for SC ABA was 31 months (IQR 30). The only association that reached statistical significance was anti-CCP concentration [Q1–Q4] (p = 0.005). According to the Cox proportional hazard regression model, there were significant differences between survival curves for Q1 (HR 0.15; 0.03–0.64 95% CI; p = 0.0096), and Q2 (HR 0.28; 0.08–0.92 95% CI; p = 0.0363) compared to the seronegative group. Conclusions The results showed an improvement in RA disease activity and physical function in patients under SC ABA treatment. Patients switching from IV to SC administration of ABA had lower activity and functional impairment at baseline. SC ABA demonstrated a good safety profile consistent with previously published data. Patients with baseline levels of anti-CCP antibody concentrations had better drug survival than seronegative patients.

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Section: Discussionmentioning

confidence: 62%

Subcutaneous abatacept in rheumatoid arthritis: A real-life experience

Sarmiento-Monroy

Parada-Arias

Rodríguez-López

et al. 2019

Journal of Translational Autoimmunity

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“…In support of the consistencies noted above, safety data from LTE studies and meta-analyses of biologic and targeted synthetic DMARDs are comparable with those reported for tofacitinib. Considering discontinuation from biologic DMARDs, 62% of patients discontinued by year 10 of treatment in an LTE study of adalimumab (23% due to AEs and 12% due to lack of efficacy/disease progression) [27]; and 31% of patients discontinued by year 5 in an LTE study of subcutaneous abatacept (31% due to AEs and 7% due to lack of efficacy) [28]. Considering safety events of special interest, previous LTE studies have reported IRs for serious infections of 3.1 and 1.7 events for adalimumab (across 10 years of treatment) and subcutaneous abatacept (across 5 years of treatment), respectively [27, 28].…”

Section: Discussionmentioning

confidence: 99%

“…Considering discontinuation from biologic DMARDs, 62% of patients discontinued by year 10 of treatment in an LTE study of adalimumab (23% due to AEs and 12% due to lack of efficacy/disease progression) [27]; and 31% of patients discontinued by year 5 in an LTE study of subcutaneous abatacept (31% due to AEs and 7% due to lack of efficacy) [28]. Considering safety events of special interest, previous LTE studies have reported IRs for serious infections of 3.1 and 1.7 events for adalimumab (across 10 years of treatment) and subcutaneous abatacept (across 5 years of treatment), respectively [27, 28]. In the integrated analysis of safety data for baricitinib, event IRs were reported for serious infections (3.0), herpes zoster (3.3), tuberculosis (0.1), MACE (0.5), DVT (0.4), PE (0.2), malignancies excluding NMSC (0.8), lymphoma (0.08), NMSC (0.4), and gastrointestinal perforation (0.04) [29, 30].…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study

et al. 2019

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Background Final data are presented for the ORAL Sequel long-term extension (LTE) study evaluating the safety and efficacy of tofacitinib 5 mg and 10 mg twice daily (BID) for up to 9.5 years in patients with rheumatoid arthritis (RA). Methods Eligible patients had previously completed a phase 1, 2, or 3 qualifying index study of tofacitinib and received open-label tofacitinib 5 mg or 10 mg BID. Stable background therapy, including csDMARDs, was continued; adjustments to tofacitinib or background therapy were permitted at investigators’ discretion. Assignment to dose groups (5 mg or 10 mg BID) was based on patients’ average total daily dose. The primary objective was to determine the long-term safety and tolerability of tofacitinib 5 mg and 10 mg BID; the key secondary objective was to evaluate the long-term persistence of efficacy. Results Between February 5, 2007, and November 30, 2016, 4481 patients were enrolled. Total tofacitinib exposure was 16,291 patient-years. Safety data are reported up to month 114 for all tofacitinib; efficacy data are reported up to month 96 for tofacitinib 5 mg BID and month 72 for 10 mg BID (with low patient numbers limiting interpretation beyond these time points). Overall, 52% of patients discontinued (24% due to adverse events [AEs] and 4% due to insufficient clinical response); the safety profile remained consistent with that observed in prior phase 1, 2, 3, or LTE studies. The incidence rate (IR; number of patients with events per 100 patient-years) for AEs leading to discontinuation was 6.8. For all-cause AEs of special interest, IRs were 3.4 for herpes zoster, 2.4 for serious infections, 0.8 for malignancies excluding non-melanoma skin cancer, 0.4 for major adverse cardiovascular events, and 0.3 for all-cause mortality. Clinically meaningful improvements in the signs and symptoms of RA and physical functioning, which were observed in the index studies, were maintained. Conclusions Tofacitinib 5 mg and 10 mg BID demonstrated a consistent safety profile (as monotherapy or combination therapy) and sustained efficacy in this open-label LTE study of patients with RA. Safety data are reported up to 9.5 years, and efficacy data up to 8 years, based on adequate patient numbers to support conclusions. Trial registration NCT00413699 , funded by Pfizer Inc (date of trial registration: December 20, 2006) Electronic supplementary material The online version of this article (10.1186/s13075-019-1866-2) contains supplementary material, which is available to authorized users.

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“…5 The long-term safety of SC abatacept showed a low incidence of serious infections, malignancies, autoimmune events, and injectionsite reactions. 6,12,[17][18][19][20][21][22][23][24][25][26] Due to the limited budget, we had only four vials of SC abatacept and to decrease the risk of side effects, we extended the intervals between doses using the frequency of initial IV abatacept doses, biweekly for three doses (i.e. a dose at weeks zero, two, and four) and the fourth dose administered at week eight.…”

Section: Discussionmentioning

confidence: 99%

Does Abatacept Induce Testicular Toxicity?

Al-Mogairen

2020

Arch Rheumatol

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Objectives: This study aims to demonstrate the effect of subcutaneous injections of abatacept on the histology of testes in mice. Materials and methods: The study included 20 male BALB/c mice (average weight, 25 g; aged 12-14 weeks). Ten mice received subcutaneous (SC) injections of abatacept (0.25 mg per 25 g body weight per 0.03 mL normal saline [NS]) at zero, two, four and eight weeks. As the control group, 10 mice received SC injections of NS (0.03 mL). At the post-injection 10 th week, the mice were sacrificed, and histopathological studies were conducted. Results: The results showed that 3/10 mice died of the abatacept-treated group. Testicular histology for the abatacept-treated group showed that 7/7 displayed no histopathological changes. Conclusion: To our knowledge, this is the first control-blinded study of BALB/c mice suggesting that abatacept may not have testicular toxicity. Further fertility and testicular toxicology evaluations including semen analysis and gonadal hormones should be performed to clarify our findings.

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Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial

Cited by 29 publications

References 17 publications

Subcutaneous abatacept in rheumatoid arthritis: A real-life experience

Subcutaneous abatacept in rheumatoid arthritis: A real-life experience

Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study

Does Abatacept Induce Testicular Toxicity?

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