ABSTRACT
Abstract Background To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). Methods This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. Results Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. Conclusions Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.
ABSTRACT
Objective:To investigate the efficacy and safety of tofacitinib (TOF) in the treatment of psoriatic arthritis (PsA).Methods:The clinical data of 5 patients with PsA from September 2018 to December 2020 in People's Hospital of Xinjiang Uygur Autonomous Region were collected. Five patients were treated with a variety of disease-modifying anti-rheumatic drugs (DMARDs), two of them had ever been treated with biologic disease-modifying antirheumatic drugs (bDMARDs) [recombinant human tumor necrosis factor-alphareceptor Ⅱ: IgG Fc (rhTNFR: Fc, Adalimumab], but failed to show efficacy or relapse after drug withdrawal. Multiple joints were involved in 2 patients. These five patients were treated with tofacitinib. Their data were collected and analyzed 3-month and 6-month after treatment respectively, including the changes of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), severity of pain measured by visual analogue scale (VAS), joint pain count (TCJ), joint swelling count (SCJ), health assessment questionnaire (HAQ), 28 joint disease activity score (DAS28 CRP), psoriasis area and severity index (PASI), and PsA disease activity index (DAPSA). Adverse reactions were observed and analyzed.Results:These 5 cases were treated with TOF 5 mg twice daily. Three months after treatment, swelling joints count and psoriatic rash were significantly improved, and pain was significantly relieved in 4 cases. Six months after treatment, the ESR, CRP, VAS, TCJ, SCJ, HAQ, DAS28 CRP, PASI, and DAPSA decreased further. According to DSA28-CRP score, peri-pheral joints involvement of 3 cases were improved, and 2 cases reached low disease activity state. The overall effective of PASI were observed in 4 cases. According to the DAPSA score, 1 case reached the PsA disease remission state and 4 cases reached the PsA low disease activity state. No remarkable adverse reactions occurred.Conclusion:With good therapeutic effect and less adverse reactions, TOF is a potential treatment option for PsA.
ABSTRACT
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate, a synthetic disease-modifying antirheumatic drug (DMARD), and biologic DMARD has revolutionized treatment of RA. Clinical remission is now realistic targets, achieved by a large proportion of RA patients, and rapid and appropriate induction of remission by intensive treatment with biological DMARD and methotrexate is prerequisite to halt joint damage and functional disabilities. However, biological DMARD is limited to intravenous or subcutaneous uses and orally available small but strong molecules have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active patients with methotrexatenaive, inadequately responsive to methotrexate or tumor necrosis factor (TNF)-inhibitors. The efficacy was rapid and as strong as adalimumab, a TNF-inhibitor. Meanwhile, association of tofacitinib on carcinogenicity and malignancy is under debate and further investigation on post-marketing survey would be warranted. On the other hand, discontinuation of a biological DMARD without disease flare is our next goal and desirable from the standpoint of risk reduction and cost effectiveness, especially for patients with clinical remission. Recent reports indicate that more than half of early RA patients could discontinue TNF-targeted biological DMARD without clinical flare and functional impairment after obtaining clinical remission. Contrarily, for established RA, fewer patients sustained remission after the discontinuation of biological DMARD and "deep remission" at the discontinuation was a key factor to keep the treatment holiday of biological DMARD.