Tofacitinib is the first oral JAK inhibitor approved for treating rheumatoid arthritis (RA). To enhance our understanding of tofacitinib drug response, we used hierarchical clustering to analyse the profiles of patient who responded to the treatment in a real-world setting. Patients who commenced on tofacitinib treatment were selected from 12 major rheumatology centres in Malaysia. The aim was to assess their response to tofacitinib defined as achieving DAS28-CRP/ESR ≤ 3.2 and DAS28 improvement > 1.2 at 12 weeks. A hierarchical clustering analysis was performed using sociodemographic and clinical parameters at baseline. All 163 RA patients were divided into three clusters (Clusters 1, 2 and 3) based on specific clinical factors at baseline including bone erosion, antibody positivity, disease activity and anaemia status. Cluster 1 consisted of RA patients without bone erosion, antibody negative, low baseline disease activity measure and absence of anaemia. Cluster 2 comprised of patients without bone erosion, RF positivity, anti-CCP negativity, moderate to high baseline disease activity score and absence of anaemia. Cluster 3 patients had bone erosion, antibody positivity, high baseline disease activity and anaemia. The response rates to tofacitinib varied among the clusters: Cluster 1 had a 79% response rate, Cluster 2 had a 66% response rate, and Cluster 3 had a 36% response rate. The differences in response rates between the three clusters were found to be statistically significant. This cluster analysis study indicates that patients who are seronegative and have low disease activity, absence of bone erosion and no signs of anaemia may have a higher likelihood of benefiting from tofacitinib therapy. By identifying clinical profiles that respond to tofacitinib treatment, we can improve treatment stratification yielding significant benefits and better health outcomes for individuals with RA.