The Relationship Between Efficacy and Toxicity in Patients with Rheumatoid Arthritis Receiving Methotrexate in Combination with Adalimumab

Gerd Burmester¹, Gurjit S. Kaeley², Arthur Kavanaugh³, Cem Gabay⁴, Daryl MacCarter⁵, Peter Nash⁶, Tsutomu Takeuchi⁷, Anabela Cardoso⁸, Shufang Liu⁹, Hartmut Kupper¹⁰ and Jasmina Kalabic¹¹, ¹Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany, ²University of Florida, Jacksonville, FL, ³University of California, San Diego School of Medicine, LaJolla, CA, ⁴Rheumatology, Geneva University Hospital, Geneva, Switzerland, ⁵Coeur d'Alene Arthritis Clinic, Coeur d'Alene, ID, ⁶Department of Medicine, University of Queensland, Brisbane, Australia, ⁷Keio University School of Medicine, Tokyo, Japan, ⁸Torre Oriente, AbbVie, Lisboa, Portugal, ⁹Immunology Development, AbbVie, North Chicago, IL, ¹⁰AbbVie Deutschland GmBH & Co. KG, Ludwigshafen, Germany, ¹¹AbbVie, North Chicago, IL

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Adalimumab, Adverse events, combination therapies, methotrexate (MTX) and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Combination
treatment of rheumatoid arthritis (RA) with methotrexate (MTX)+adalimumab
(ADA) has been shown to be more effective than ADA monotherapy. However, MTX is
associated with known toxicity. Here we
assessed the relationship between MTX-related toxicity and achieved efficacy of
ADA+MTX treatment.

Methods: Data were from 2 randomized controlled
trials. In CONCERTO¹, early RA patients (pts) initiated ADA + 2.5,
5, 10 or 20 mg/week (wk) MTX for 26 wks. In MUSICA², pts with
moderate-severe RA and an inadequate response to MTX initiated ADA + 7.5 or 20
mg/wk MTX for 24 wks. Efficacy was assessed by ACR50. MTX toxicity was assessed
by collecting information from pts at each visit on 18 pre-specified MTX-
related adverse events (AE) reported in the MTX product label: abnormal hair
loss or sweating, chronic dry cough, conjunctivitis, dizziness, excessive
fatigue/malaise, fever and/or chills, infection, nausea and/or vomiting, oral ulcers,
skin pigment changes, rash/hives, stomach discomfort, tinnitus, unexplained
visual changes/diarrhea or weight loss. The observed efficacy of initiated
ADA+concomitant MTX, and MTX-related AE are reported.

Results: In CONCERTO, pts were MTX–naïve. During
the study, the mean duration of MTX exposure was 174.6
days. Overall, 113/395 pts (28.6%) reported 345 MTX-related AEs, including 1
serious AE (SAE, excessive fatigue and/or malaise); 10 events (in 2 pts) led to
discontinuation. Pts in the 10/20 mg MTX groups reported the most AE. Pts in
the 20 mg MTX group had both, the highest ACR response rate, and MTX-related AE.
For each MTX dosage group, AE rates remained steady, whereas ACR50 response
rates to ADA + MTX increased over time (Fig 1A). At Wk 26, the ACR50 response rates
ranged from 54- 68%; MTX-related AE rates ranged from 2.4-17.8%. In MUSICA, the mean duration of prior
MTX exposure was 1.5 yrs; mean prior MTX dosage was 17.3 mg/wk. During the study, the mean duration of MTX exposure was 157.5
days. Overall, 71/309 pts
(23%) reported 185 MTX-related AEs; including 5 SAEs (4 infections and 1 fever
and/or chills); 6 events (in 4 pts) led to discontinuation. MTX-related AE were
reported at similar rates for both MTX dosage groups and peaked at Wk 4, whereas
ACR50 response rates increased with time for both groups (Fig 1B). At Wk 24,
the ACR50 response rates were 32.3% and 37.5% while the MTX-related AE rate was
6.5%.

Conclusion: In pts with early and established RA
initiating ADA in combination with MTX, treatment efficacy was achieved despite
reported MTX-related toxicity. Most MTX-related AE were mild and led to study
discontinuation in 0.5% and 1.3% pts in CONCERTO and MUSICA respectively. While
rates of MTX -related AE remained steady, efficacy of ADA+MTX increased during
both trials.

Ref: 1) Burmester GR et al. ARD
2014; 0:1-8. 2) Kaeley GS
et al. ACR 2013 Ann Meeting, Boston, MA, USA: S1147

Disclosure: G. Burmester, Abbvie, Pfizer, UCB, Roche, 2,Abbvie, Bristol-Myers Squibb, Pfizer, Merck, MedImmune, UCB, Roche, 5,Abbvie, Bristol-Myers Squibb, Pfizer, Merck, UCB, Roche, 8; G. S. Kaeley, AbbVie, 5; A. Kavanaugh, AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, 9; C. Gabay, AbbVie, Amgen, BMS, MSD, Pfizer, Roche, Celgene, Sanofi, Regeneron, 9; D. MacCarter, AbbVie, 9; P. Nash, Abbvie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli-Lilly, Novartis, Celgene, 9; T. Takeuchi, Chugai Pharmaceutical Co,. Ltd., 2; A. Cardoso, AbbVie, 9; S. Liu, AbbVie, 9; H. Kupper, AbbVie, 9; J. Kalabic, AbbVie, 9.

To cite this abstract in AMA style:

Burmester G, Kaeley GS, Kavanaugh A, Gabay C, MacCarter D, Nash P, Takeuchi T, Cardoso A, Liu S, Kupper H, Kalabic J. The Relationship Between Efficacy and Toxicity in Patients with Rheumatoid Arthritis Receiving Methotrexate in Combination with Adalimumab [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-relationship-between-efficacy-and-toxicity-in-patients-with-rheumatoid-arthritis-receiving-methotrexate-in-combination-with-adalimumab/. Accessed .

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-relationship-between-efficacy-and-toxicity-in-patients-with-rheumatoid-arthritis-receiving-methotrexate-in-combination-with-adalimumab/