Biologics-treated Patients Research Articles

Risk of infections of biological and targeted drugs in patients with spondyloarthritis: meta-analysis of randomized clinical trials.

Background:Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).Methods:A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool.Results:In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07–1.26, P < 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26–2.17, P < 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04–1.32, P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10–1.42, P < 0.001), and Candida infection (Peto OR: 2.64, 95% CI: 1.48–4.71, P = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-a inhibitors (Peto OR: 1.38, 95% CI: 1.13–1.68, P = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08–2.22, P = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14–1.69, P = 0.001); higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26–9.55, P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38–2.91, P < 0.001); higher risk of URTI for TNF-a inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05–1.78, P = 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08–2.36, P = 0.018); higher risk of nasopharyngitis for TNF-a inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05–1.90, P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09–2.05, P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01–1.82, P = 0.044); higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03–4.62, P = 0.043); higher risk of Candida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31–4.84, P = 0.006).Conclusions:This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, and Candida infection, which should be paid attention to in our clinical practice.

Risk of Malignancy and Tuberculosis of Biological and Targeted Drug in Patients With Spondyloarthritis: Systematic Review and Meta-analysis of Randomized Controlled Trials.

Objective: Concerns exist regarding the potential development of malignancy and tuberculosis in patients with spondyloarthritis (SpA) treated with biologics. We assessed the extent to which biologic therapy may increase the risk of malignancy and tuberculosis in patients with SpA by meta-analysis to derive estimates of sparse harmful events occurring in Randomized Controlled Trials (RCTs). Methods: A systematic literature search was conducted in PubMed, EMbase, Web of Science, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating the risk of sparse harmful events of biologic therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto OR for malignancy and tuberculosis in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using Cochrane Risk of Bias tool. Results: In total, 63 studies were included in this meta-analysis, and 83 patients and 7 patients developed malignancy and tuberculosis, respectively. Overall, the risk of malignancy and tuberculosis was increased in SpA patients treated with biologics compared to placebo (malignancy: Peto OR: 2.49, 95%CI: 1.61–3.87, p < 0.001; tuberculosis: Peto OR: 5.98, 95%CI: 1.29–27.76, p = 0.022). Remarkably, compared to placebo, there was higher risk of malignancy for IL-17 inhibitors (Peto OR: 3.68, 95%CI: 1.20–11.30, p = 0.023) and small molecule targeted drugs (Peto OR: 3.08, 95%CI: 1.37–6.90, p = 0.043) in peripheral SpA, and for TNF receptor-Fc fusion protein in axial SpA (Peto OR: 7.18, 95%CI: 1.21–42.69, p = 0.030). Besides, the risk of tuberculosis was higher for anti-TNFα antibody in axial SpA (Peto OR: 6.17, 95%CI: 1.03–37.13, p = 0.046). Conclusion: This meta-analysis showed an elevated risk of malignancy in patients with peripheral SpA treated with biologics, especially for IL-17 inhibitors, and small molecule targeted drugs, a slightly increased risk of malignancy in TNF receptor-Fc fusion protein in axial SpA, and increased risk of tuberculosis in patients with axial SpA treated with anti-TNFα antibody. These findings need to be validated by studies with larger population and longer follow-up.

Gastrointestinal perforations in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs in Sweden: a nationwide cohort study

ObjectivesTo compare incidence rates of gastrointestinal (GI) perforations between patients with RA and the general population, and between patients treated with tumour necrosis factor inhibitors (TNFi) and non-TNFi biologics.MethodsIn this...

Risk of medical complications following total hip or knee arthroplasty in patients with rheumatoid arthritis: A register-based cohort study from Denmark

ObjectiveTo investigate the risk of medical complications following total hip and knee arthroplasty (THA/TKA) among rheumatoid arthritis (RA) compared with osteoarthritis (OA) patients; and, to assess the risk of complications among biologics-treated RA patients. MethodsIn a nationwide register-based study, patients with RA and OA with THA/TKA surgery between 2000 and 2015 were identified and followed up to 90 days after surgery for venous thromboembolism (VTE), myocardial infarction and stroke, and non-surgical infections, respectively. Information on treatment with biologics was obtained in the DANBIO rheumatology register to compare risks of complications with non-biologics treated. ResultsA total of 2899 and 112,571 patients with RA and OA had THA/TKA. RA was associated with a hazard ratio (HR) of 1.29 (1.03 to 1.61) for infection following THA/TKA, but a HR of 0.60 (0.26 to 0.98) for VTE following TKA. Biologics treated patients had a HR of 1.35 (0.65 to 2.80) for infection and 4.82 (1.67 to 13.90) for VTE compared with non-biologics treated RA patients. RA patients had no increased risk of post-surgical myocardial infarction and stroke (HR 1.16, 0.76 to 1.78) compared with OA, but a higher incidence proportion was observed in biologics treated compared with non-biologics treated (1.0% vs 0.6%); however, the number of events were too small to estimate a HR. ConclusionIn this study, RA was a risk factor for infection after THA/TKA, and RA patients treated with biologics had a slightly increased risk compared with non-biologics treated RA patients. Compared with OA, RA patients had a lower risk of VTE following THA/TKA, but our finding of increased incidences of VTE in biologics-treated patients warrants further studies.

Long-term use of biologic agents does not increase the risk of serious infections in elderly patients with rheumatoid arthritis

This study aimed to determine whether the long-term use of biologic agents increases serious infections in elderly patients with rheumatoid arthritis (RA) and to determine the risk factors of serious infections in biologics-treated elderly RA patients. We retrospectively analyzed the incidence rate of serious infections that required hospitalization between biologics-treated and non-biologic disease-modifying antirheumatic drug (DMARD)-treated elderly RA patients (aged over 65 years). We examined the risk factors for serious infections in biologics-treated elderly RA patients. We found that, during a 3-year observation period, the incidence rate of serious infections was not significantly different between biologics-treated and non-biologic DMARD-treated elderly RA patients [8.0 (95% CI 4.7–13.5) and 6.3 (95% CI 4.1–9.5) events per 100 person-years of follow-up, respectively, P = 0.78]. The time to the first serious infection did not significantly differ between the two groups by the analysis of the Kaplan–Meier curves, either (P = 0.46). We then found that prednisolone doses alone were significantly associated with serious infections in biologics-treated elderly RA patients. Furthermore, we found that prednisolone at 1–4 mg/day was associated with serious infections in biologics-treated patients, but not non-biologic DMARD-treated patients. On the other hand, prednisolone at greater than 5 mg/day was associated with serious infections in both biologics-treated and non-biologics-treated patients. We show that there is not a significant difference between the incidence of serious infections between biologics group and non-biologics group in elderly RA patients (≧65 years) and that even very low-dose glucocorticoid use (prednisolone 1–4 mg/day) is a risk factor for serious infections in biologics-treated elderly RA patients.

Characterizing patients with psoriasis on injectable biologics adalimumab, etanercept, and ustekinumab: A chart review study

Objective: This study examined plaque psoriasis (PsO) patient characteristics across injectable biologics. Methods: Data were collected from 400 US dermatologists randomly selecting five charts each for patients with PsO (patient n = 2000): adalimumab (ADA; n = 447), etanercept (ETA; 539), ustekinumab (UST) 45 mg (511) and UST 90 mg (503). Physicians had to have been in practice 2–30 years, managing 10+ patients (5 + with biologics for PsO). Generalized estimating equation models, weighted according to inverse probability of patient selection and accounting for patient correlation within physicians, examined patient measures as a function of treatment (UST 90 mg = reference). Results: Patients on UST 90 mg had higher odds of weighing >100 kg (adjusted mean = 34.4%) vs. ADA (10.9%), ETA (5.5%) or UST 45 mg (6.8%), greater body surface affected and higher odds of severe PsO prior to treatment and higher odds of prior biologics use. Mean prior biologics used was higher with UST 90 mg versus ADA or ETA. Number of comorbidities was higher with UST 90 mg versus ETA or UST 45 mg. Conclusions: Among biologics-treated patients with PsO, UST 90 mg appears to be used in patients with greater weight, baseline severity and prior biologics experience than ADA, ETA or UST 45 mg. UST 90 mg is used in patients with more comorbidities than other treatments except ADA.

Biologics are more potent than other treatment modalities for improvement of quality of life in psoriasis patients.

Although mental health is hampered in various skin disorders, few studies regarding anxiety in psoriasis patients are available, and specifically, no evaluation exists between mental health and psoriasis severity or the patients' quality of life. To examine the relation between mental health, psoriasis severity and patient's quality of life, 119 psoriasis vulgaris patients were assessed for anxiety using the General Health Questionnaire (GHQ)-30. Psoriasis area and severity index (PASI) and Dermatological Life Quality Index (DLQI) scores were also measured. The average total GHQ-30 score was significantly decreased from 4.41 to 2.11 (52.2% decrease) in biologics-treated patients. That of patients treated with other systemic agents decreased from 4.36 to 3.32 (23.9% decrease) and that of those treated with topical agents from 4.21 to 3.48 (17.3% decrease). In the biologics-treated group five of the six categories of GHQ-30, i.e., general illness, somatic symptoms, sleep disturbance, social dysfunction, and anxiety and dysphoria, were significantly decreased after the treatment. In contrast, in the other systemic treatment and topical treatment groups, three of the six categories, general illness, somatic symptoms, and sleep disturbance were significantly decreased. There was a significant correlation between GHQ-30 and DLQI, but not with PASI. The psoriasis patients show impaired mental health and among various treatment modalities biologics are superior to other systemic or topical treatments for improving the defective mental state.

AB1105 Epidemiological Assessment of Baseline Characteristics of the Abatacept-Treated Patients in Select Real-World Rheumatoid Arthritis Data Sources

BackgroundRegistries in North America and Europe have reported that patients with RA initiating abatacept are in poorer health, more likely to be previously exposed to several biologics and to have...

Listeriosis in patients receiving biologic therapies

The evolution of inflammatory diseases has radically changed since the introduction of biologic therapies, such as tumour necrosis factor alpha inhibitors (anti-TNFα). They, therefore, represent a widely used therapeutic modality. Nevertheless, post-marketing studies reveal an increased risk of infection in patients taking these drugs, especially granulomatous infections such as listeriosis. We aimed to evaluate the reported cases of listeriosis in patients treated with biologic treatments. We used the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) from 2004 to 2011. We also perform a literature review of previously reported cases of listeriosis in patients taking biologic therapies. We identified 266 cases of Listeria monocytogenes infection associated with biologic therapies. The majority of patients were receiving infliximab (77.1 %), followed by etanercept (11.7 %), adalimumab (9.8 %), rituximab (4.1 %), abatacept (0.4 %) and golimumab (0.4 %). Indications for the use of biologics were as follows: 47.7 % for rheumatologic diseases, 38 % for inflammatory bowel diseases, 3.4 % for haematological diseases and 10.5 % for other indications. Seventy-three percent of the patients were receiving concomitant immunosuppressant drugs, especially steroids (56 %) and methotrexate (31.6 %). The median time to the onset of infection was 184 days. Mortality rates range from 11.1 % in adalimumab-treated patients to 27.3 % in rituximab-treated patients (p = 0.7). Listeriosis is common in biologics-treated patients, especially related to infliximab use given concomitantly with other immunosuppressive therapies. Infections after treatment with biologics mostly occurred in the first year after initiating treatment.