Evaluation of abatacept administered subcutaneously in adults with active rheumatoid arthritis: impact of withdrawal and reintroduction on immunogenicity, efficacy and safety (phase Iiib ALLOW study)

Kaine, Jeffrey; Gladstein, Geoffrey; Strusberg, Ingrid; Robles, Manuel; Louw, Ingrid; Gujrathi, Sheila; Pappu, R.; Delaet, Ingrid; Pans, Miranda; Ludivico, Charles

doi:10.1136/annrheumdis-2011-200344

Cited by 60 publications

(72 citation statements)

References 14 publications

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“…This is consistent with previous clinical trial reports of SC ABA use, and further demonstrates that the frequency of SC injection-site reactions is reduced with increasing treatment time 8,9 .…”

Section: Rheumatologysupporting

confidence: 81%

“…Further, immunogenicity did not appear to affect the safety or efficacy of SC ABA. Comparisons of data from this study with other ABA studies are problematic given immunogenicity has previously been evaluated using ELISA, rather than ECL 7,8,9,10,11,18 . There are a number of differences between the 2 assay types; notably, ECL has a greatly increased sensitivity compared to ELISA (12.2 ng/ml vs 275 µg/ml).…”

Section: Rheumatologymentioning

confidence: 93%

“…A subcutaneous (SC) formulation of ABA is also available. Four phase II or III trials have investigated the tolerability and clinical effectiveness of a weekly fixed dose of 125 mg SC ABA, demonstrating low immunogenicity with safety and efficacy similar to that of the IV formulation 7,8,9,10,11 .…”

mentioning

confidence: 99%

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Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

Genovese

Pacheco‐Tena²,

Covarrubias³

et al. 2014

J Rheumatol

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Objective.Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA).Methods.The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported.Results.Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8–44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA.Conclusion.These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).

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Section: Rheumatologysupporting

confidence: 81%

Section: Rheumatologymentioning

confidence: 93%

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Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

Genovese

Pacheco‐Tena²,

Covarrubias³

et al. 2014

J Rheumatol

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“…However, no increase in autoimmune disorders was observed with ABA treatment over the 5-year LTE period. As previously reported, the rate of immunogenic response was low for ABA, with no increase observed with continued dosing over the study period 18 . Importantly, there was no association between development of anti-ABA antibodies and ABA safety or efficacy over the 5-year period, or pharmacokinetics over the tested period through Day 729.…”

Section: Rheumatologysupporting

confidence: 50%

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

Genovese

Pacheco‐Tena²,

Covarrubias³

et al. 2018

J Rheumatol

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Objective.To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA).Methods.The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported.Results.Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96–8.58), infection 38.60 (36.24–41.12), serious infection 1.68 (1.35–2.07), malignancies 1.09 (0.84–1.42), and autoimmune disorders 1.33 (1.05–1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study.Conclusion.These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

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“…The expressions of antibodies to TCZ may reduce efficacy and systemic reactions to injections of anti‐TNF inhibitors would occasionally cause lack of efficacy due to the expression of antidrug antibodies 16, 17, 18, 19. In a previous study, we found the anti‐TCZ antibody frequency to be increased in TCZ‐SC patients as compared to TCZ‐IV patients in the double‐blind setting 9.…”

Section: Discussionmentioning

confidence: 84%

Sustainable Efficacy of Switching From Intravenous to Subcutaneous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis

Ogata

Atsumi

Fukuda

et al. 2015

Arthritis Care & Research

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ObjectiveTo evaluate the efficacy and safety of switching from intravenous (IV) tocilizumab (TCZ) to subcutaneous (SC) TCZ monotherapy in rheumatoid arthritis patients.MethodsPatients who had completed 24 weeks of TCZ‐SC (162 mg/2 weeks) or TCZ‐IV (8 mg/kg/4 weeks) monotherapy in the double‐blind period of the MUSASHI study were enrolled in an 84‐week open‐label extension period. All received TCZ‐SC (162 mg/2 weeks) monotherapy. Effects of the IV to SC switch were evaluated at week 36 (12 weeks after switching).ResultsOverall, 319 patients received ≥1 dose of TCZ‐SC during the open‐label extension period; 160 switched from TCZ‐IV to TCZ‐SC (TCZ IV/SC) and 159 continued TCZ‐SC (TCZ SC/SC). Disease Activity Score in 28 joints using the erythrocyte sedimentation rate clinical remission rates were 62.5% (100 of 160) for TCZ IV/SC and 50.0% (79 of 158) for TCZ SC/SC at week 24, and were maintained at 62.5% (100 of 160) and 57.0% (90 of 158), respectively, at week 36. In the TCZ IV/SC group, 9% of patients (9 of 100) who had achieved remission at week 24 could not maintain remission at week 36. In TCZ IV/SC patients weighing ≥70 kg, the percentage with a sufficient serum TCZ concentration (≥1 μg/ml) decreased from 90.9% (10 of 11) at week 24 to 45.5% (5 of 11) at week 36. Overall safety profiles were similar in TCZ IV/SC and TCZ SC/SC except for mild injection site reactions in TCZ IV/SC.ConclusionEfficacy is adequately maintained in most patients switching from TCZ‐IV (8 mg/kg/4 weeks) to TCZ‐SC (162 mg/2 weeks) monotherapy. Patients receiving TCZ‐IV can switch to TCZ‐SC without serious safety concerns. Clinical efficacy may be reduced after switching in some patients with high body weight.

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Evaluation of abatacept administered subcutaneously in adults with active rheumatoid arthritis: impact of withdrawal and reintroduction on immunogenicity, efficacy and safety (phase Iiib ALLOW study)

Cited by 60 publications

References 14 publications

Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

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

Sustainable Efficacy of Switching From Intravenous to Subcutaneous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis

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