Certolizumab Pegol for Fatigue in Chronic Inflammatory Rheumatic Diseases: A Meta-Analysis

Yesim Ozguler¹, Sinem Nihal Esatoglu¹, Guzin Karatemiz¹, Ali Ugur Unal², Gul Guzelant¹, Elif Dincses³, Mustafa Erdogan¹, Sema Kaymaz Tahra² and Gulen Hatemi¹, ¹Istanbul University, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey, ²Departement of Internal Medicine, Division of Rheumatology, Marmara University, Istanbul, Turkey, ³Istanbul University, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Rheumatology, İstanbul, Turkey

Meeting: ACR/ARHP Annual Meeting 2017

Date of first publication: September 18, 2017

Keywords: certolizumab pegol, Fatigue, meta-analysis, rheumatoid arthritis (RA) and spondylarthritis

Session Information

Date: Sunday, November 5, 2017

Title: Rheumatoid Arthritis – Clinical Aspects Poster I: Treatment Patterns and Response

Session Type: ACR Poster Session A

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

Background/Purpose: Fatigue is an important problem that impairs life quality in patients with rheumatic diseases. Although fatigue is often associated with disease activity, only a modest effect of anti-TNFs on fatigue was observed in patients with RA (1). We aimed to determine the efficacy of different doses of certolizumab pegol (CZP) in chronic inflammatory rheumatic diseases by a meta-analysis of randomized controlled trials.

Methods: A systematic literature search including patients with rheumatic diseases who received CZP was performed. We searched PubMed for all randomized controlled trials with CZP up to May 2017 without any restrictions. Studies that assessed fatigue in any rheumatic disease using the fatigue assessment scale (FAS) and reported the FAS score and/or the proportion of patients who met the minimum clinically important difference (MCID) for FAS score were included. The MCID for FAS is 1 over a scale of 0 to 10 where higher scores show increased severity of fatigue. The CZP 200 mg and CZP 400 mg arms of trials were pooled for comparison with the placebo arms.

Results: The literature search yielded 68 articles. 55 articles were excluded after evaluating the title and abstract, 5 were excluded after reading the full-text. Among the 8 RCTs that were selected , the study population was RA in 6 RCTs, and psoriatic arthritis and axial spondyloarthritis in 1 RCT each. Overall, there were 2964 patients treated with CZP and 1056 with placebo. Table summarizes the included studies.

An improvement in the FAS score and an increase in the proportion of patients who met the MCID for FAS were observed in all the included trials regardless of the underlying disease (Figure-1, 2). The pooled results showed that CZP significantly improved fatigue compared to placebo (FAS: MD = -1.50, 95% CI:-1.71- -1.29, p <0.0001, MCID: RR=2.53, 95% CI: 1.74-3.68).

Conclusion: This meta-analysis showed that CZP may be an effective treatment modality for fatigue in rheumatic diseases.

Reference:

1) Druce KL, Bhattacharya Y, Jones GT, Macfarlane GJ, Basu N. Most patients who reach disease remission following anti-TNF therapy continue to report fatigue: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Rheumatology (Oxford). 2016 Oct;55(10):1786-90

Table 1. Characteristics of randomized controlled studies included in the meta-analysis
First author, year	Disease state	Inclusion criteria	Intervention arm	Comparator arm	Number of patients (M/W)			Study duration (weeks)
First author, year	Disease state	Inclusion criteria	Intervention arm	Comparator arm	CZP 400	CZP 200	Placebo
Fleischman, 2017	RA	Active disease despite ≥1 DMARD	CZP 400	Placebo every 4 weeks	111 (24/87)	NA	109 (12/97)	24
Furst, 2015	RA	Active disease despite MTX	CZP 400 CZP 200	Placebo every 2 weeks	70 (12/58)	70 (23/49)	69 (14/56)	34
Pope, 2015	RA	Active disease despite ≥1 DMARD	CZP 200	Placebo every 2 weeks	NA	851 (NR)	221 (NR)	12
Smolen, 2017	RA	Low/moderate active despite ≥1 DMARD	CZP 200	Placebo every 2 weeks	NA	96 (15/81)	98 (23/75)	24
Strand, 2009	RA	Active disease despite MTX	CZP 400 CZP 200	Placebo every 2 weeks	390 (64/326)	393 (69/324)	199 (32/167)	52
Strand, 2011	RA	Active disease despite MTX	CZP 400 CZP 200	Placebo every 2 weeks	246 (54/192)	246 (42/206)	127 (20/107)	24
Gladman, 2014	pSA	Active disease despite ≥1 DMARD*	CZP 400 CZP 200	Placebo every 2 weeks	135 (62/73)	138 (64/74)	136 (57/79)	24
Sieper, 2015	axial SpA	Active disease despite ≥1 NSAID*	CZP 400 CZP 200	Placebo every 2 weeks	107 (68/39)	111 (67/44)	107 (65/43)	24
*An history of an anti-TNF failure was not an exclusion criterion DMARD: disease modifying anti-rheumatic drug; pSA; psoriatic arthritis; SpA: spondyloarthritis; MTX methotrexate, NSAID: non-steroidal anti-inflammatory drugs; CZP: certolizumab pegol; NA: not applicable; NR: not reported

Disclosure: Y. Ozguler, None; S. N. Esatoglu, None; G. Karatemiz, None; A. U. Unal, None; G. Guzelant, None; E. Dincses, None; M. Erdogan, None; S. Kaymaz Tahra, None; G. Hatemi, None.

To cite this abstract in AMA style:

Ozguler Y, Esatoglu SN, Karatemiz G, Unal AU, Guzelant G, Dincses E, Erdogan M, Kaymaz Tahra S, Hatemi G. Certolizumab Pegol for Fatigue in Chronic Inflammatory Rheumatic Diseases: A Meta-Analysis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/certolizumab-pegol-for-fatigue-in-chronic-inflammatory-rheumatic-diseases-a-meta-analysis/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/certolizumab-pegol-for-fatigue-in-chronic-inflammatory-rheumatic-diseases-a-meta-analysis/