Tofacitinib Monotherapy in Rheumatoid Arthritis: Clinical Trials and Real-World Data Contextualization of Patients, Efficacy, and Treatment Retention

Figures & data

Table 1 Demographics and Baseline Disease Characteristics for Patients Receiving Tofacitinib Monotherapy in Clinical Trials and Available RWD Sources

	Clinical Trial Data			RWD
				Harnett et al^Citation14		Reed et al^Citation15 (N=238)	Bird et al^Citation16 (N=282)
	Group 1^a (N=627)	Group 2^b (N=373)	Group 3^c (N=498)	Truven Market-Scan^® (N=176)	Optum^® Clinformatics^® (N=60)
Age, years
Median (range)	52.0 (21.0–81.0)	52.0 (18.0–76.0)	56.0 (19.0–82.0)	-	-	-	-
Median (IQR)	-	-	-	-	-	59 (52–68)	-
Mean (SD)	50.7 (12.0)	50.3 (12.2)	54.7 (11.5)	55.7 (11.7)	55.8 (13.3)	-	62.0 (12.2)
Female, n (%)	526 (83.9)	286 (76.7)	424 (85.1)	141 (80.1)	46 (76.7)	193 (81.1)	226 (80.1)
Race, n (%)
White	449 (71.6)	239 (64.1)	232 (46.6)	-	-	197 (82.8)	-
Asian	82 (13.1)	68 (18.2)	216 (43.4)	-	-	-	-
Black	23 (3.7)	13 (3.5)	5 (1.0)	-	-	-	-
Other	73 (11.6)	53 (14.2)	45 (9.0)	-	-	-	-
Disease duration
Median (range), years	5.8 (0.2–42.3)	0.8 (0.0–44.0)	5.5 (0.0–38.0)	-	-	-	-
Median (IQR), years	-	-	-	-	-	10 (5–16)	-
Median, months	-	-	-	-	-	-	138.5
Mean (SD), years	8.3 (7.9)	2.9 (5.4)	7.7 (7.6)	2.9 (1.3)	3.0 (1.3)	-
CDAI
Median (range)	38.5 (10.7–75.3)	37.5 (11.5–74.3)	33.6 (11.8–71.9)	-	-	-	-
Median (IQR)	-	-	-	-	-	17.9 (9.8–27.0)	-
Joint count, mean (SD)
TJC	16.0 (6.6)	15.3 (6.6)	12.9 (6.6)	-	-	-	7.3 (7.7)
SJC	11.3 (5.4)	11.7 (5.6)	10.5 (5.0)	-	-	-	6.9 (7.6)
Concomitant glucocorticoids, n (%)	358 (57.1)	175 (46.9)	277 (55.6)	156 (88.6)	54 (90.0)	65 (27.3)^d	-
Glucocorticoid dose, mean (SD), mg/day	4.3 (9.1)	3.6 (5.7)	6.2 (3.4)	-	-	4.4 (1.0)^d	-
csDMARD use, n (%)	-	-	-	116 (65.9)	36 (60.0)	-	-
Prior MTX use, n (%)	593 (94.6)	24 (6.4)	44 (8.8)	-	-	-	-
Prior non-MTX csDMARD use, n (%)	279 (44.5)	138 (37.0)	33 (6.6)	-	-	-	-
Prior bDMARD use, n (%)	-	-	-	149 (84.7)	43 (71.7)	215 (90.3)^e	-
Prior TNFi use	25 (4.0)	0	1 (0.2)	-	-	-	-
Prior non-TNFi bDMARD use	31 (4.9)	0	2 (0.4)	-	-	-	-

Notes: All patients included in the clinical trial groups received tofacitinib 5 mg BID monotherapy; only patients who received tofacitinib 5 mg BID monotherapy throughout the LTE studies were included in Group 3. Patients in Group 3 enrolled in the LTE studies from any index study (ie not limited to ORAL Solo, ORAL Strategy, or ORAL Start) and could have received index dosages other than tofacitinib 5 mg BID. N may vary for specific endpoints. - represents where the variable of interest was not reported. ^aORAL Solo (NCT00814307) and ORAL Strategy (NCT02187055). ^bORAL Start (NCT01039688). ^cORAL Sequel (NCT00413699) and Japanese study (NCT00661661). ^dConcomitant glucocorticoids were prednisone. ^eValue calculated based on bDMARD-naïve patients without taking into account any potentially missing patients.

Abbreviations: RWD, real-world data; N, total number of patients; IQR, interquartile range; SD, standard deviation; n, number of patients with characteristic; CDAI, Clinical Disease Activity Index; TJC, tender joint count; SJC, swollen joint count; csDMARD, conventional synthetic disease-modifying antirheumatic drug; MTX, methotrexate; bDMARD, biologic disease-modifying antirheumatic drug; TNFi, tumor necrosis factor inhibitor; BID, twice daily; LTE, long-term extension.

Figure 1 Rates of achieving (A) CDAI-defined LDA (≤10), (B) CDAI-defined remission (≤2.8), (C) DAS28-4(ESR)-defined LDA (≤3.2), and (D) DAS28-4(ESR)-defined remission (<2.6) in patients receiving tofacitinib monotherapy in clinical trials^a and available RWD sources.

Notes: ^aAll patients included in the clinical trial groups received tofacitinib 5 mg BID monotherapy; only patients who received tofacitinib 5 mg BID monotherapy throughout the long-term extension studies were included in Group 3. Patients in Group 3 enrolled from any index study (ie not limited to ORAL Solo, ORAL Strategy, or ORAL Start), and they could have received index dosages other than 5 mg BID. ^bORAL Solo (NCT00814307) and ORAL Strategy (NCT02187055). ^cORAL Start (NCT01039688). ^dUS CorEvitas registry.^{15 e}RWD data are observed values (ie no imputation) with no available SE. ^fORAL Sequel (NCT00413699) and Japanese study A3921041 (NCT00661661). BID, twice daily; CDAI, Clinical Disease Activity Index; DAS28-4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; LDA, low disease activity; n, number of patients achieving outcome; N, total number of patients; RWD, real-world data; SE, standard error.

Figure 2 Rates of achieving (A) DAS28-4(CRP)-defined LDA (≤3.2)^a and (B) DAS28-4(CRP)-defined remission (<2.6)^a in patients receiving tofacitinib monotherapy in clinical trials^b and available RWD sources.

Notes: ^aLDA and remission values for DAS28-4(CRP) (≤3.2 and <2.6, respectively) have not been validated but are commonly used in rheumatology. ^bAll patients included in the clinical trial groups received tofacitinib 5 mg BID monotherapy; only patients who received tofacitinib 5 mg BID monotherapy throughout the long-term extension studies were included in Group 3. Patients in Group 3 enrolled from any index study (ie not limited to ORAL Solo, ORAL Strategy, or ORAL Start), and they could have received index dosages other than 5 mg BID. ^cORAL Solo (NCT00814307) and ORAL Strategy (NCT02187055). ^dORAL Start (NCT01039688). ^eORAL Sequel (NCT00413699) and Japanese study A3921041 (NCT00661661). ^fOPAL dataset.^{16 g}RWD data are observed values (ie no imputation) with no n/N numbers and SE available. BID, twice daily; DAS28-4(CRP), Disease Activity Score in 28 joints, C-reactive protein; LDA, low disease activity; n, number of patients achieving outcome; N, total number of patients; OPAL, Optimizing Patient outcomes in Australian rheumatoLogy; RWD, real-world data; SE, standard error.

Figure 3 Kaplan–Meier plots of time to discontinuation of tofacitinib 5 mg Bid monotherapy due to lack of efficacy or adverse events in clinical trials^a: (A) Group 1, (B) Group 2, and (C) Group 3.

Notes: ^aAll patients included in the clinical trial groups received tofacitinib 5 mg BID monotherapy; only patients who received tofacitinib 5 mg BID monotherapy throughout the long-term extension studies were included in Group 3. Patients in Group 3 enrolled from any index study (ie not limited to ORAL Solo, ORAL Strategy, or ORAL Start), and they could have received index dosages other than tofacitinib 5 mg BID.^bORAL Solo (NCT00814307) and ORAL Strategy (NCT02187055). ^cORAL Start (NCT01039688). ^dORAL Sequel (NCT00413699) and Japanese study A3921041 (NCT00661661). BID, twice daily.

Harnett J, Curtis JR, Gerber R, Gruben D, Koenig A. Initial experience with tofacitinib in clinical practice: treatment patterns and costs of tofacitinib administered as monotherapy or in combination with conventional synthetic DMARDs in 2 US health care claims databases. Clin Ther. 2016;38(6):1451–1463. doi:10.1016/j.clinthera.2016.03.038

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Reed GW, Gerber RA, Shan Y, et al. Real-world comparative effectiveness of tofacitinib and tumor necrosis factor inhibitors as monotherapy and combination therapy for treatment of rheumatoid arthritis. Rheumatol Ther. 2019;6(4):573–586. doi:10.1007/s40744-019-00177-4

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Bird P, Littlejohn G, Butcher B, et al. Real-world evaluation of effectiveness, persistence, and usage patterns of monotherapy and combination therapy tofacitinib in treatment of rheumatoid arthritis in Australia. Clin Rheumatol. 2022;41(1):53–62. doi:10.1007/s10067-021-05853-x

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Data Sharing Statement

Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.