Rheumatoid arthritis (RA) is a chronic, debilitating disease characterized by synovial inflammation and joint erosion. In Mexico, RA has an estimated prevalence rate of 1.6%1 and its prevalence among the working population represents a significant economic burden.2 As tuberculosis is endemic to Mexico, the global practice of screening for tuberculosis prior to initiating biologic disease-modifying antirheumatic drugs (bDMARDs) is particularly important in Mexico.3 In Mexico, RA is most commonly treated with conventional synthetic DMARDs (csDMARDs) and non-steroidal anti-inflammatory drugs.4 Only 6% of patients are treated with bDMARDs.4 Mexican College of Rheumatology (CMR) guidelines3 recommend csDMARD therapy immediately following RA diagnosis, with methotrexate as first choice, unless contraindicated. For patients with an inadequate response to csDMARDs, treatment with tumor necrosis factor inhibitors (TNFi) is suggested; tofacitinib is recommended following failed biologic treatment.3

Globally 30–40% of patients do not respond to csDMARDs, and 20–30% of patients treated with bDMARDs still have active disease,5 highlighting the need for alternative therapies to address issues of tolerability and inadequate response.

Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The efficacy and safety of tofacitinib as monotherapy or in combination with csDMARDs have been reported in global Phase 36–11 and long-term extension (LTE)12 studies and in the overall Latin American (LA) subpopulation.13

Here we assessed tofacitinib efficacy and safety in Mexican patients with RA from global Phase 3 and LTE studies.

In this analysis of Mexican patients from the tofacitinib global RA program, tofacitinib reduced the signs and symptoms of RA and improved physical function, when administered as monotherapy or in combination with csDMARDs up to 12 Months in Phase 3, and up to 36 Months in the LTE study. Although formal statistical comparisons were not conducted, tofacitinib efficacy in Mexican patients was generally consistent with that observed in the global7,8,10–12 and LA13 Phase 3 and LTE analyses; however, a greater proportion of Mexican patients were female and Mexican patients were typically younger. The small sample sizes in the subpopulations precluded statistical comparison between treatment groups and formal conclusions being drawn regarding the efficacy and safety of tofacitinib. These factors should be considered in interpreting outcomes.

The safety profile of tofacitinib in Mexican patients was generally similar with respect to the Phase 3 and LTE global7,8,10–12 and LA analyses,13 including low and comparable IRs of opportunistic infections (excluding tuberculosis), tuberculosis, malignancies (excluding NMSC), and MACE in LTE study analyses. As in the global LTE study,12 there were increases in hemoglobin levels and decreases in absolute neutrophil and lymphocyte counts in the Mexican LTE study population.

Patients with RA have a greater risk of infections, including tuberculosis, that increases with use of immunosuppressive agents and bDMARDs.15 In LA, registry data on the use of bDMARDs16,17 also indicated increased risk of infections and tuberculosis with therapy. In this analysis, no SIEs or tuberculosis occurred during Phase 3 studies and there were no opportunistic infections and only two cases of tuberculosis reported during the LTE study. However, it should be acknowledged that the Mexican subpopulation is small, and patients participating in tofacitinib Phase 3 and LTE studies were screened for active or latent tuberculosis.

In the global RA program, IRs for HZ were generally higher with tofacitinib versus placebo and bDMARDs18; the overall HZ risk was particularly increased in Japanese and Korean patients. The IRs (unique patients with events/100 patient-years) of HZ in Mexican tofacitinib-treated patients in the LTE analysis presented here were numerically lower with tofacitinib 5mg BID and similar with 10mg BID compared with the global LTE analysis (4.2 [95% CI 3.5, 5.0] and 4.5 [3.8, 5.4] for tofacitinib 5 and 10mg BID, respectively),12 but higher than those reported in analyses of registry data for bDMARD-treated patients with RA in the UK19 (1.6 events/100 patient-years), US20 (1.2 events/100 patient-years) and Germany21 (1.1 events/100 patient-years). In interpreting the rate of HZ observed in these analyses, it should be noted that patients with history of recurrent HZ, disseminated HZ or herpes simplex were not permitted to be enrolled in these studies.

In light of CMR recommendations,3 tofacitinib's oral administration route may be of benefit in reducing the number of clinic visits required by patients. Moreover, unlike bDMARDs, which are administered via injection and with which patients may lose response owing to acquired drug resistance,22 tofacitinib is an oral small molecule therapy and patients with RA may prefer treatment in the form of a tablet over injectable therapies.23 Accordingly, tofacitinib offers an alternative for Mexican patients with RA who failed treatment with csDMARDs. A further potential benefit of a small molecule therapy for RA in the Mexican healthcare setting may be a reduction in administrative costs owing to fewer required patient visits to the clinic and independence from temperature-controlled supply chains. However, an evaluation of the pharmacoeconomic impact of tofacitinib for RA therapy was not included in this study, and additional studies should be performed to assess this.

Compared to the tofacitinib global study population, the number of patients, tofacitinib exposure and treatment duration were lower in these subpopulation analyses which may explain the lower rates of long-latency AEs such as MACE and malignancies. Interpretation of the Phase 3 data in this analysis was limited by pooling of data from studies with different patient populations, study designs, and methodologies. Fewer patients were enrolled in the placebo groups of Phase 3 studies and consequently patient exposure was lower. In interpreting the Phase 3 efficacy analyses, it should also be noted that patients remaining in the placebo group at Month 6 were those from ORAL Scan, Sync, and Standard who had at least 20% improvement in both tender/painful and swollen joint counts at Month 3 and this may explain the relatively high response rate observed for some efficacy endpoints (e.g. ACR20/50) in the placebo group at Month 6. Interpretation of the data from the LTE study was limited by its observational nature. Furthermore, the tolerability and efficacy of tofacitinib have already been demonstrated in patients enrolling in the LTE study through their index study participation. Dose adjustments were also permitted in the LTE, limiting comparison between tofacitinib doses. Nonetheless, due scarce long-term real-life data, LTE data and real-world data studies24 are important in evaluating tofacitinib in the Mexican subpopulation.

Tofacitinib 5mg BID and 10mg BID showed improvement in efficacy endpoints which were sustained with long-term therapy up to 36 months post-index study. The safety profile of tofacitinib in Mexican patients with RA was consistent with that of the LA and global populations.

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  Sustained efficacy in reducing signs and symptoms of RA was observed up to 36 months in Mexican patients treated with tofacitinib in the LTE study.

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  The safety profile of tofacitinib in the Mexican subpopulation was consistent with that observed in the global and overall Latin American Phase 3 and LTE study populations.

R Burgos-Vargas has received research grants, consultancy fees, and/or speakers’ fees from AbbVie, Janssen, Lilly, Novartis, Pfizer Inc., and UCB.

MH Cardiel has received research grants, consultancy fees, and speakers’ fees from AbbVie, Astellas, Astra Zeneca, Bristol-Myers Squibb, Infinity, Janssen, Lilly, Merck-Serono, Pfizer Inc, Roche, and UCB.

D Xibillé has received consultancy fees from Pfizer Inc. and payment for clinical studies from AstraZeneca, Bristol-Myers Squibb, Janssen, Pfizer Inc., and UCB.

C Pacheco-Tena has received payment for clinical studies, consultancy fees, or speaker fees from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Lilly, Merck-Serono, Novo Nordisk, Pfizer Inc, Roche, Sanofi, UCB, and Vertex.

V Pascual-Ramos has nothing to disclose.

C Abud-Mendoza has received consultancy fees and speaker fees from Bristol-Myers Squibb, Pfizer Inc, and Roche and speaker fees from Merck-Serono and UCB.

EY Mahgoub, H Fan, R Rojo, and K Santana are employees and shareholders of Pfizer Inc. MU Rahman and EG García were employees and shareholders of Pfizer Inc at the time the analyses were conducted.