Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis

Abstract

Objectives: To assess the impact of baseline RF level on drug concentrations and efficacy of certolizumab pegol [CZP; TNF inhibitor (TNFi) without a crystallizable fragment (Fc)] and adalimumab (ADA; Fc-containing TNFi) in patients with RA.

Methods: The phase 4 EXXELERATE study (NCT01500278) was a 104-week, randomized, single-blind (double-blind until week 12; investigator-blind thereafter), head-to-head study of CZP vs ADA in patients with RA. In this post hoc analysis, we report drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3).

Results: Baseline data by RF quartiles were available for 453 CZP-randomized and 454 ADA-randomized patients (≤Q3: ≤204 IU/ml; >Q3: >204 IU/ml). From week 12, the area under the curve (AUC) of ADA concentration was lower in patients with RF >204 IU/ml vs patients with RF ≤204 IU/ml; the AUC of CZP concentration was similar in patients with RF ≤204 IU/ml and >204 IU/ml. For patients with RF ≤204 IU/ml, disease activity score (DAS28)-CRP was similar between CZP- and ADA-treated patients through week 104. For patients with RF >204 IU/ml, mean DAS28-CRP was lower in CZP- vs ADA-treated patients at week 104. The proportion of patients with RF >204 IU/ml achieving DAS28-CRP low disease activity at week 104 was greater in CZP- vs ADA-treated patients.

Conclusion: CZP was associated with maintained drug concentration and efficacy in patients with RA and high RF and may therefore be a more suitable therapeutic option than TNFis with an Fc fragment in these patients.

Trial registration: Clinicaltrials.gov, http://clinicaltrials.gov, NCT01500278.

Keywords: RA; RF; TNF inhibitor.

Figure 1.

Mean drug plasma concentrations of (A) CZP and (B) ADA to week 104, stratified by RF quartile at baseline (OC). Full analysis set to week 12; week 12 full analysis set from week 18. Data reported according to the treatment patients were on at the time of measurement (i.e. any patients who had switched TNFi at week 12 were subsequently included in the arm for their new treatment, rather than the arm they were initially randomized to). ADA: adalimumab; CZP: certolizumab pegol; OC: observed case; Q3: third quartile; TNFi: TNF inhibitor

Figure 2.

Response to CZP and ADA to week 104 measured by (A) DAS28-CRP and (B) DAS28-CRP LDA, stratified by RF quartile at baseline (OC; NRI). Full analysis set to week 12; week 12 full analysis set from week 18. Data reported according to the treatment patients were on at the time of measurement (i.e. any patients who had switched TNFi at week 12 were subsequently included in the arm for their new treatment, rather than the arm they were initially randomized to). N is for OC data. (a) Defined as DAS28-CRP ≤2.7. (b) N at week 2. ADA: adalimumab; CZP: certolizumab pegol; DAS28: Disease Activity Score-28 joint count; LDA: low disease activity; NRI: non-responder imputation; OC: observed case; Q3: third quartile; TNFi: TNF inhibitor

Figure 3.

Response to CZP and ADA to week 104 measured by (A) CDAI and (B) CDAI LDA, stratified by RF quartile at baseline (OC). Full analysis set to week 12; week 12 full analysis set from week 18. Data reported according to the treatment patients were on at the time of measurement (i.e. any patients who had switched TNFi at week 12 were subsequently included in the arm for their new treatment, rather than the arm they were initially randomized to). (a) Defined as CDAI ≤10. (b) N at week 2. ADA: adalimumab; CDAI: Clinical Disease Activity Index; CZP: certolizumab pegol; OC: observed case; Q3: third quartile; TNFi: TNF inhibitor

Figure 4.

Response to CZP and ADA to week 104 measured by (A) DAS28-CRP and (B) DAS28-ESR, stratified by ACPA level at baseline (OC). Full analysis set to week 12; week 12 full analysis set from week 18. Data reported according to the treatment patients were on at the time of measurement (i.e. any patients who had switched TNFi at week 12 were subsequently included in the arm for their new treatment, rather than the arm they were initially randomized to). ACPA: anti-citrullinated protein antibody; ADA: adalimumab; CZP: certolizumab pegol; DAS28: Disease Activity Score-28 joint count; OC: observed case; Q3: third quartile; TNFi: TNF inhibitor