Abstract
BackgroundRheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients with RA are at increased risk of malignancy, however, it remains unclear whether the combination therapy is associated with a higher risk.ObjectiveTo assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone.MethodsPubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel–Haenszel random-effect method.Results659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found.ConclusionThe adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA.
Highlights
Rheumatoid arthritis (RA) is a systemic autoimmune disease, estimated to affect approximately 0.5% to 1% of population [1]
The adjunction of Janus kinase inhibitor (JAKi) to MTX is not associated with an increased risk of malignancy when compared to MTX alone
ACRAmerican college of rheumatology, CRP C-reactive protein, CDAI clinical disease activity index, DAS28 disease activity score 28, ESR erythrocyte sedimentation rate, EULAR European League Against Rheumatism, FACIT-F functional assessment of chronic illness therapy fatigue scale, HAQ-DI health assessment questionnaire disability index, IR inadequate response, LDA low disease activity, MCID minimum clinically important difference, MTX methotrexate, NA not available, PCS physical component score, PGA physician’s global assessment of disease activity, PRO patient reported outcomes, RA rheumatoid Arthritis, SF-36 short-form 36, SDAI simplified disease activity index, SJC swollen joint count, TNF-alpha tumor necrosis factor-alpha, TJC total joint count, vdH-mTSS van der Heijde-modified total sharp score in serious adverse events (SAE) (Fig. 6) and Risk ratio (RR) = 1.99 in deaths (Fig. 7)
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease, estimated to affect approximately 0.5% to 1% of population [1]. Patients with RA are predisposed to an increased risk for malignancy, especially malignant lymphomas [2–7], lung cancers [5, 6] and non-melanoma skin cancer [7]. Solipuram et al Autoimmun Highlights (2021) 12:8 with the presence of cancer, varied by stage of malignancy [8]. Persistent inflammation triggers the development and progression of cancer [9, 10]. It has been well-established that severity of inflammation in RA is positively correlated with the risk of lymphoma [11]. Taking the inflammation into control may reduce the risk of developing malignancy. Rheumatoid arthritis (RA) is a systemic autoimmune disease. Patients with RA are at increased risk of malignancy, it remains unclear whether the combination therapy is associated with a higher risk
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