Effectiveness of Certolizumab-Pegol in Rheumatoid Arthritis, Spondyloarthritis, and Psoriatic Arthritis Based on the BIOPURE Registry: Can Early Response Predict Late Outcomes?

BACKGROUND: Identification of predictors of clinical response to certolizumab-pegol (certolizumab) may aid the decision-making process for treating patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). OBJECTIVE: The aim of our study was to evaluate the effectiveness of certolizumab and identify any predictors of favorable outcome in patients with RA, PsA, or SpA. METHODS: We studied 355 RA, SpA, and PsA patients starting treatment with certolizumab. Endpoints of the study were drug survival and identification of predictors of clinical outcome. Drug retention was analyzed via the Kaplan-Meier method, and hazard ratios (HRs) were estimated using Cox regression models. RESULTS: Of 355 certolizumab initiators, 178 had RA, 94 had PsA, and 83 had SpA. Biologic-naïve RA patients had significantly higher survival rates (73.3%) than switchers taking certolizumab as a second-line (49.0%) or third- or next-line biologic agent (51.2%; p = 0.0001). Instead, PsA and SpA patients showed similar drug retention rates regardless of the line of treatment. A significant clinical improvement from baseline was seen at 3 months for RA (28 joint-Disease Activity Score [DAS28]; p = 0.001), PsA (Disease Activity Index for PsA [DAPSA]; p = 0.001), and SpA (Bath Ankylosing Disease Index; p = 0.01). Biologic-naïve patients had the lowest HR (0.31; p = 0.001) of discontinuing certolizumab for RA, and the highest HR (7.94; p = 0.01) of achieving minimal disease activity (MDA) for PsA. For PsA, a predictor of late MDA was the achievement of low/remission DAPSA at 3 months, and 3-month low/remission DAS28 predicted late remission for RA. CONCLUSIONS: Our study revealed that the best predictor of certolizumab effectiveness in unselected patients with RA, PsA, or SpA was a biologic-naïve status and achievement of an early response within 3 months.

Correction to: Drug survival and effectiveness of ustekinumab in patients with psoriatic arthritis. Real-life data from the biologic Apulian registry (BIOPURE).

In Fig. 1 - paned D, incorrect image was published. This is now presented correctly in this article.

Drug survival and effectiveness of ustekinumab in patients with psoriatic arthritis. Real-life data from the biologic Apulian registry (BIOPURE).

This study aims to evaluate the drug survival and effectiveness of ustekinumab in psoriatic arthritis (PsA) patients naïve to biologics or inadequate responders to tumor necrosis factor (TNF-IR) inhibitors in real life. PsA patients starting ustekinumab were enrolled from 2014 to 2016. Joint involvement, peripheral or axial, Psoriatic Area Severity Index, Disease Activity Psoriatic Arthritis (DAPSA), Lee Enthesitis Index, Health Assessment Questionnaire, body mass index, comorbidities, co-therapies, mechanism of action, and causes of discontinuation of prior TNFi were collected at baseline, and 6 and 12 months. Twelve-month drug survival was evaluated by Kaplan-Meier curves. Hazard ratios (HRs) of drug discontinuation adjusted for baseline factors were estimated by multiple Cox regression analysis. Percentages of DAPSA-based remission, as crude value and adjusted for drug retention (LUNDEX index), were compared by χ2 test. Mean differences of DAPSA from baseline to 6 and 12 months were compared between naïve and TNF-IR patients by ANOVA. Of 160 PsA patients starting ustekinumab, 54 were naïve and 106 were TNF-IR. Twelve-month drug survival was significantly higher in naïve (87%) than in TNF-IR (68%, p = 0.01). Baseline co-therapy with methotrexate did not increase the persistence on ustekinumab. Naïve patients had the lowest risk of ustekinumab discontinuation (HR 0.27, p = 0.01), and the highest DAPSA-based remission (34%, LUNDEX 26%). Mean differences from baseline of DAPSA was significantly greater in naïve than in TNF-IR patients at 12 months (- 14.4 ± 10 vs. - 4.1 ± 17, p = 0.01). Our data showed that ustekinumab has a good effectiveness in real life and the best outcomes are achieved in biologic-naïve PsA patients.

Effective tumour necrosis factor-blocking therapy reduces reactive oxygen metabolite level in rheumatoid arthritis.

OBJECTIVE: To assess circulating levels of derived reactive oxygen metabolites (ROMs) in patients with active rheumatoid arthritis (RA), before and during antitumour necrosis factor (TNF)-α therapy. METHODS: Patients with active RA and failed previous treatment with disease-modifying antirheumatic drugs received subcutaneous anti-TNF-α for 52 weeks. Circulating hydrogen peroxide was quantified as a marker of oxidative stress at baseline and at 24 and 52 weeks. RESULTS: The study included 40 patients. Circulating dROM levels were significantly reduced compared with baseline after 24 and 52 weeks' of anti-TNF-α treatment (33.2 ± 10.0 mgH2O2/dl, 29.5 ± 7.0 mgH2O2/dl and 29.3 ± 9.0 mgH2O2/dl, respectively). There was a significant direct correlation between disease activity score and ROM levels. CONCLUSION: TNF-α inhibition can control disease activity and reduce circulating levels of reactive oxygen species in patients with RA.

Leflunomide treatment in elderly patients with rheumatoid or psoriatic arthritis: retrospective analysis of safety and adherence to treatment.

BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) play a crucial role in the treatment of persistent chronic synovitis, such as active rheumatoid arthritis (RA) and spondyloarthritis, by inducing or maintaining disease remission, reducing the frequency of flares or relapses, and allowing corticosteroids to be tapered while maintaining disease control. OBJECTIVE: The aim of this retrospective study was to evaluate the safety of, and adherence to treatment with, leflunomide in elderly RA and psoriatic arthritis patients compared with younger patients. METHODS: A total of 90 Italian patients (80 with active RA and 10 with psoriatic arthritis) were retrospectively examined at entry and after 24 months' follow-up. Patients were divided into two groups according to age: those aged 65 years (n = 40). Each patient was analysed for clinical, demographic and laboratory parameters in order to evaluate liver, renal and haematological toxicity. Disease Activity Score including a 28-joint count (DAS28) and physician global assessment of disease activity (MD global) were measured to define disease activity. RESULTS: During the 24-month follow-up period, 30 patients (33.3%) discontinued leflunomide: 17 patients (34.0%) in the group of patients aged 65 years. There were no differences in treatment withdrawal between the two groups. Overall, 10 patients (11.1%) in the entire study population discontinued leflunomide for lack of efficacy, while 21 (23.3%) discontinued the drug because of adverse effects (one patient withdrew because of both inefficacy and adverse effects). There were no significant differences in efficacy or adverse effects between patients aged 65 years. There was also no significant difference in survival rates of leflunomide treatment when patients aged 65 years (p = 0.94). There were no significant differences in withdrawal rates in the overall population when leflunomide monotherapy was compared with leflunomide combination therapy. There were also no significant differences in the types of adverse effects associated with monotherapy or combination therapy when the two age groups were compared. CONCLUSIONS: Leflunomide is a useful and well tolerated DMARD for the treatment of RA and psoriatic arthritis in the elderly. The safety profile of, and adherence to, leflunomide is not different in older patients with chronic inflammatory joint diseases such as RA or psoriatic arthritis to that observed in younger patients.