Background/Purpose: Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The clinical development program for tofacitinib in RA enrolled ˃500 patients (pts) aged ≥65 years (yrs). Rates of infection and other conditions seen in pts with RA typically increase with age. This analysis evaluated the efficacy and safety of tofacitinib in older (≥65 yrs) and younger pts (<65 yrs).

Methods: Efficacy was evaluated in a post-hoc, pooled analysis of four Phase (P) 2 and five P3 studies (ORAL Solo, ORAL Sync, ORAL Scan, ORAL Standard and ORAL Step). Efficacy results for rates of ACR20/50/70 and improvement from baseline in HAQ-DI ≥0.22 were reported as probability ratios (PRs; proportion of responders in tofacitinib group divided by placebo [PBO] at Month 3) with 95% confidence intervals. Pts randomized to PBO advanced to tofacitinib beginning at Month 3. Safety was evaluated in a post-hoc pooled analysis of five P3 studies (Month 0-12) and a pooled analysis of two ongoing long-term extension (LTE) studies. Incidence rates for safety endpoints were compared in older vs younger pts.

Results: A total of 3439 pts received tofacitinib 5 mg, tofacitinib 10 mg, or PBO, twice daily (BID), and 520 were aged ≥ 65 years. PRs for rates of ACR20/50/70 and HAQ-DI improvement in older pts treated with tofacitinib 5 mg BID (N=196) vs PBO (N=122) were 1.86 (1.42-2.42), 2.84 (1.72-4.70), 3.32 (1.49-7.42) and 1.23 (1.02-1.50) respectively, which were similar to, or slightly lower than, the PRs for other age groups (not shown). PRs for tofacitinib 10 mg BID vs PBO were numerically slightly higher for all outcomes. The rate of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) was generally higher in older than in younger pts irrespective of treatment group. The rate of serious infection events (SIE) was greater by 6.2/100 pt yrs in older pts who received tofacitinib vs PBO; the corresponding rate difference in younger pts was 0.9/100 pt yrs (Table). Herpes zoster (HZ) rates were higher in tofacitinib pts vs PBO, and HZ rates for tofacitinib-treated pts were similar irrespective of age. MACE, or malignancies, did not occur in older pts receiving PBO in any of the P3 studies and were infrequent in both age groups of tofacitinib-treated pts (Table). Safety results for older and younger pts in LTE studies were generally consistent with P3 study results.

Conclusion: Older pts (≥65 yrs) treated with tofacitinib were observed to be at increased risk of SIEs vs older pts treated with PBO, consistent with reports from multiple RA pt databases of biologic DMARDs (Listing et al 2013). Older pts generally were at increased risk of SAEs and discontinuations due to AEs vs younger pts (<65 yrs). The benefit-risk profile of tofacitinib must be taken into account when considering treatment of older pts with RA.

Table. Incidence rates for key safety endpoints by age group and treatment in five tofacitinib Phase 3 studies

Age group (yrs)	Younger pts (<65)			Older pts (≥65)
Treatment group	PBO	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	PBO	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of patients	580	1026	1030	101	190	184
Serious adverse events
N	23	76	67	7	28	20
Exposure (pt-yrs)	171.4	748.2	766.4	28.3	124.4	124.8
Incidence rate /100 pt yrs (CI)	13.4 (8.9-20.2)	10.1 (8.1-12.7)	8.7 (6.9-11.1)	24.7 (11.8-51.9)	22.5 (15.5-32.5)	16.0 (10.4-25.0)
Discontinuations due to adverse events
N	21	76	74	4	19	25
Exposure (pt-yrs)	172.7	767.3	778.8	28.8	130.6	126.6
Incidence rate /100 pt yrs (CI)	12.2 (7.9-18.6)	9.9 (7.9-12.4)	9.5 (7.6-11.9)	13.9 (5.2-37.0)	14.5 (9.3-22.8)	19.7 (13.3-29.2)
Serious infections
N	3	19	21	0	10	6
Exposure (pt-yrs)	173.6	769.9	781.7	28.9	131.0	127.3
Incidence rate /100 pt yrs (CI)	1.7 (0.6-5.4)	2.5 (1.6-3.9)	2.7 (1.8-4.1)	0	7.6 (4.1-14.2)	4.7 (2.1-10.5)
Herpes zoster
N	3	35	31	0	4	7
Exposure (pt-yrs)	172.8	756.0	768.7	28.9	129.7	126.6
Incidence rate /100 pt yrs (CI)	1.7 (0.6-5.4)	4.6 (3.3-6.4)	4.0 (2.8-5.7)	0	3.1 (1.2-8.2)	5.5 (2.6-11.6)
Opportunistic infections
N	0	2	7	0	1	3
MACE
N	2	2	2	0	2	4
All malignancies (excluding NMSC)
N	0	3	7	0	2	1
BID, twice daily; CI, 95% confidence interval; MACE, major adverse cardiovascular events; N, number of cases; NMSC, non-melanoma skin cancer; PBO, placebo; pt, patient; yrs, years

 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-tofacitinib-in-older-and-younger-patients-with-rheumatoid-arthritis/