Tocilizumab Had Acceptable Retention Rate in Both Randomized Controlled Trials and Observational Studies: Systematic Review of Rheumatoid Arthritis

Levent Kilic¹, Orhan Kucuksahin², Zeynep Ozbalkan³, Cemal Bes⁴, Veli Yazisiz⁵, Ayten Yazici⁶, Dilek Solmaz⁷, Timucin Kasifoglu⁸ and Umut Kalyoncu⁹, ¹Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey, ²Rheumatology, Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey, ³Rheumatology, Ankara Numune Education and Research Hospital, Ankara, Turkey, ⁴Rheumatology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey, ⁵Rheumatology, Akdeniz University Faculty of Medicine, Ankara, Turkey, ⁶Department of Rheumatology, Kocaeli University, Faculty of Medicine, Kocaeli, Turkey, ⁷Rheumatology, Katip Çelebi University Faculty of Medicine, İzmir, Turkey, ⁸Rheumatology, Eskisehir Osmangazi University Faculty of Medicine, Eskişehir, Turkey, ⁹Department of Internal Medicine, Divison of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: rheumatoid arthritis (RA) and tocilizumab

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: In general, retention rate in biological DMARDs represent both efficacy and safety. Tocilizumab (TOC) is a humanized monoclonal antibody that binds to the interleukin-6 receptor. So far, TOC was used in randomized controlled trials (RCTs) and longitudinal observational studies (LOSs), as well. The aim of this study was to assess the retention rate of TOC for the treatment of RA patients in RCTs and LOS.

Methods: In January 2017, a systematic Review (SR) was performed in PUBMED MEDLINE. Publications were identified using the MeSH terms: (‘‘rheumatoid arthritis and Tocilizumab’’) with a limitation to ‘‘humans’’, ‘‘all adults: 19+ years’’, ‘‘English’’ and ‘‘clinical trials’’. All available studies describing the retention rate of TOC were recruited to SR. Retention rate of TOC were calculated according to route (SC or IV), dosage (4 mg/kg vs 8 mg/kg), monotherapy or combination with methotrexate. Of the 662 publications identified by the literature search, 42 were recruited in the analysis. Retention rates of TOC at 12-16 weeks, 24-32 weeks, 48-52 weeks, 2. Years, 3. Years and 5. years were analyzed. Open label extension period of RCTs included to LOS. The causes of withdrawals of TOC were recorded as inefficacy, adverse event, and others.

Results: Of the 42 studies, 11 (26.2%) were RCTs and 31 (73.8%) were LOSs. Totally 20590 patients (15574 (75.6%) female) were pooled to analysis that 4817 patients (23.4%) were from RCTs. The mean age was 56.2 years and mean disease duration was 10.1 years. Seropositivity was 75.0% for rheumatoid factor and 76.5% for ACPA. Overall, 8934 (44.4%) of patients were biologic-naïve. TOC was used as monotherapy (5111/16323, 31.3%), or concomitant with methotrexate (11976/19522, 61.4%). Available baseline DAS-28 score, CDAI, SDAI, and HAQ-DI score were 5.8, 30.4, 32.5, and 1.46 respectively. Retention rates of TOC intravenous 8 mg/kg at 48-52 weeks, 2. year, 3. year and 5. year were 75.5 – 85.2%, 48.4 – 76.1%, 69.9%, 66.2%, respectively. Retention rate and causes of withdrawal of TOC according to study type were shown in Table 1.

Conclusion: Both RCTs and LOSs, withdrawal of TOC was particularly well known in 24-32. weeks. TOC intravenous 8 mg/kg also had satisfactory retention rate in 48-52 weeks, 2. year, 3. year and 5. year. Moreover, retention rate of TOC in LOSs was comparable with other biologic DMARDs, as well.

Table 1: Retention Rate of Tocilizumab in Randomized Controlled Trials and Observational Studies

Durations (weeks)	Study Type	Patients number	Route and dosage	Continue of TOC (%)	Causes of Withdrawals (%)
					Inefficacy	Adverse event	Others
12-16 w	RCTs	102	iv, 8 mg/kg	85.3	20.0	53.3	26.7
	RCTs	103	iv, 4 mg/kg	82.5	33.3	50.0	16.7
	LOS	551	iv, 8 mg/kg	88.0	27.5	31.4	41.2
24-32 w	RCTs	3198	iv, 8 mg/kg	92.7	13.8	67.7	25.2
		377	iv, 4 mg/kg	85.9	NA	NA	NA
		1242	sc, 162 mg	92.2	19.7	46.5	33.8
	LOS	12488	iv, 8 mg/kg	83.3	29.0	44.1	27.0
48-52 w	RCTs	209	iv, 8 mg/kg	85.2	25.8	38.7	35.5
48-52 w	LOS	3761	iv, 8 mg/kg	74.5	34.4	31.5	34.1
2. years	RCTs	209	iv, 8 mg/kg	76.1	26.0	38.0	38.0
2. years	LOS	649	iv, 8 mg/kg	48.4	–	–	–
3. years	LOS	114	iv, 8 mg/kg	69.9	20.0	10.0	40.0
5. years	LOS	240	iv, 8 mg/kg	66.2	7.4	61.7	30.9
TOC:Tocilizumab, RCT: Randomized Controlled Trials, LOS: Long Observational Studies, iv: intravenous, sc:subcutaneous

Disclosure: L. Kilic, Roche Pharmaceuticals, 5; O. Kucuksahin, Roche Pharmaceuticals, 5; Z. Ozbalkan, Roche Pharmaceuticals, 5; C. Bes, Roche Pharmaceuticals, 5; V. Yazisiz, Roche Pharmaceuticals, 5; A. Yazici, Roche Pharmaceuticals, 5; D. Solmaz, Roche Pharmaceuticals, 5; T. Kasifoglu, Roche Pharmaceuticals, 5; U. Kalyoncu, Roche Pharmaceuticals, 5.

To cite this abstract in AMA style:

Kilic L, Kucuksahin O, Ozbalkan Z, Bes C, Yazisiz V, Yazici A, Solmaz D, Kasifoglu T, Kalyoncu U. Tocilizumab Had Acceptable Retention Rate in Both Randomized Controlled Trials and Observational Studies: Systematic Review of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/tocilizumab-had-acceptable-retention-rate-in-both-randomized-controlled-trials-and-observational-studies-systematic-review-of-rheumatoid-arthritis/. Accessed .

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