Safety of the JAK and TNF inhibitors in rheumatoid arthritis: real world data from the Hong Kong Biologics Registry.

OBJECTIVES: To compare the incidence of major adverse cardiovascular events (MACEs), cancer and infective complications in RA patients using Janus kinase (JAKis) and TNF (TNFis) inhibitors. METHOD: A retrospective analysis of data from the Hong Kong Biologics Registry 2008-2021 was performed. RA patients who had ever used JAKis or TNFis were included. The incidence of MACEs, cancer and infections were compared between the two groups, with adjustment for confounding factors. RESULTS: A total of 2471 courses of JAKis (n = 551) and TNFis (n = 1920) were used in 1732 RA patients (83.7% women, age 53.8 [12.5] years; follow-up 6431 patient-years). JAKi users had significantly older age, more atherosclerotic risk factors and higher frequency of past malignancies. A total of 15 and 40 MACEs developed in the JAKi and TNFi users, respectively (incidence 1.34 vs 0.75 per 100 patient-years; P = 0.22). There was no significant difference in the incidence of cancers between the two groups (0.81 [JAKi] vs 0.85 [TNFi] per 100 patient-years; P = 0.25). The adjusted hazard ratios of MACE and cancer in the JAKi users were 1.36 (95% CI: 0.62, 2.96) (P = 0.44) and 0.87 (95% CI: 0.39, 1.95) (P = 0.74), respectively. Rates of infections were significantly higher in the JAKi than TNFi users (16.3 vs 9.9 per 100 patient-years; P = 0.02), particularly herpes zoster (3.49 vs 0.94 per 100 patient-years; P < 0.001). CONCLUSIONS: In a real-life setting, there is no increase in MACEs or cancers in users of JAKis compared with TNFis. However, the incidence of non-serious infections, including herpes zoster, was increased in users of JAKis.

A case report of rheumatoid neutrophilic dermatitis in a Chinese woman with seropositive rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory arthritis associated with a number of extra-articular manifestations. We report the case of a rare extra-articular manifestation of seropositive RA in a 48-year-old woman. She developed spontaneously remitting pustular rashes on the dorsum of both hands which recurred during periods of a high disease activity. Skin biopsy revealed rheumatoid neutrophilic dermatosis (RND), a rare skin manifestation of RA. Both RA and RND were controlled with rituximab therapy. Clinical presentations and differential diagnoses were discussed. Tight control of RA is pivotal in the management of RA and extra-articular manifestations.

Outcome and prognostic indicators of diffuse proliferative lupus glomerulonephritis treated with sequential oral cyclophosphamide and azathioprine.

OBJECTIVE: To study the outcome and prognostic indicators of diffuse proliferative glomerulonephritis (DPGN) in patients with systemic lupus erythematosus (SLE) treated with sequential oral cyclophosphamide (CYC) and azathioprine (AZA). METHODS: SLE patients with biopsy-proven DPGN treated with sequential oral CYC and AZA were studied. Those who achieved renal remission at 12 months were identified, and the clinical predictors of complete remission were evaluated by regression analysis. All patients were followed up until a relapse of the nephritis or a doubling of the serum creatinine level occurred. The timing and risk factors for flares and creatinine doubling were evaluated by Kaplan-Meier analysis and with the Cox proportional hazards model. RESULTS: We studied 55 patients (47 women, 8 men; mean +/- SD age at renal biopsy 31.1 +/- 10.4 years); 25 (46%) had a serum creatinine level >106 micromoles/liter, and 29 (53%) had nephrotic syndrome. At 12 months posttreatment, 37 (67%) had complete remission and 12 (22%) had partial remission. The initial serum creatinine level was an independent predictor of complete remission. Excluding the 4 patients who were treatment- resistant or died, 21 patients (41%) had renal flares during a median followup of 4 years. The cumulative risk of renal flare was 6% at 1 year, 21% at 3 years, and 32% at 5 years. The median time to relapse was 43 months. The histologic activity score and the mean daily dose of CYC were multivariate predictors of renal flare, by Cox regression. At the last followup visit, 9 of 54 patients (17%) had a doubling of the creatinine level, 6 of whom (11%) underwent dialysis. The cumulative risk of creatinine doubling was 8.4% at 5 years and 18.2% at 10 years. An increasing chronicity index at the time of initial renal biopsy was an independent predictor of deterioration in renal function. CONCLUSION: Sequential therapy with oral CYC followed by AZA appears to be an effective treatment regimen for DPGN in patients with SLE, with 89% of patients achieving complete or partial remission at 12 months, 62.8% remaining in remission after 5 years, and 81.8% having stable renal function after 10 years. Predictors of treatment resistance and relapse include increasing serum creatinine level, higher histologic activity scores, and a lower dose of CYC. Increasing chronicity indices predict a deterioration of renal function.