Therapy Of Rheumatic Diseases Research Articles

Rheumatoid arthritis - medication dosage in chronic kidney disease.

Renal failure in the course of rheumatoid arthritis (RA) is a consequence of many factors, including drug-induced nephrotoxicity, comorbidities and chronic inflammation. Contemporary treatment strategies have reduced the incidence of renal failure in the population of RA patients. However, it remains a problem for approximately 25% of patients. Therefore, special attention should be paid to the potential need for dosage modifications of administered medications. Many drugs used in the therapy of rheumatic diseases have not been thoroughly studied for their safety in patients with reduced glomerular filtration, resulting in limited data in this area. The establishment of precise, transparent, and consistent dosage recommendations for antirheumatic drugs in chronic kidney disease would significantly facilitate the care of patients with RA. The following review provides a general summary of the available knowledge regarding the dosage of rheumatic medications in renal insufficiency and aims to highlight the need for further research in this area.

Changes in Arterial Stiffness Monitored Using the Cardio-Ankle Vascular Index in Patients with Rheumatic Disease Receiving Initial Glucocorticoid Therapy: A Clinical Pilot Study.

Systemic inflammatory rheumatic diseases predispose to premature birth, accelerated atherosclerosis, and increased cardiovascular disease (CVD). While glucocorticoids (GCs) are used in various rheumatic diseases, and the associations between GC excess and increased prevalence of CVD complications are well established, the mechanisms underlying GCs' role in atheroma development are unclear. We conducted an observational study to address GC therapy's effect on arterial stiffness using the cardio-ankle vascular index (CAVI) in patients with rheumatic diseases. Twenty-eight patients with rheumatic disease received initial GC therapy with prednisolone at doses ranging from 20 to 60 mg/d. CAVI was examined at baseline and 3 and 6 months after GC therapy. Changes in CAVI and inflammatory parameters were evaluated. GC therapy increased the mean CAVI after 3 months but decreased it to pretreatment levels after 6 months. The mean CAVI substantially decreased with GC treatment in patients <65 years but increased in patients ≥65 years. Alterations in CAVI during the 6-month GC treatment negatively correlated with the lymphocyte-to-monocyte ratio (LMR) at baseline. Conversely, no correlation was observed between alterations in CAVI values and conventional inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). Multivariate analysis of factors related to changes in CAVI highlighted young age, high prednisolone dosage, and LMR at baseline. GC temporarily exacerbates but eventually improves arterial stiffness in rheumatic diseases. Particularly in young patients, GC may improve arterial stiffness by reducing inflammation. Therefore, the LMR before GC therapy in rheumatic diseases may be a potential predictor of arterial stiffness.

Safety outcomes in patients with rheumatoid arthritis treated with abatacept: results from a multinational surveillance study across seven European registries

BackgroundPatients with rheumatoid arthritis (RA) have an increased risk of infection and malignancy compared with the general population. Infection risk is increased further with the use of disease-modifying antirheumatic drugs (DMARDs), whereas evidence on whether the use of biologic DMARDs increases cancer risk remains equivocal. This single-arm, post-marketing study estimated the incidence of prespecified infection and malignancy outcomes in patients with RA treated with intravenous or subcutaneous abatacept.MethodsData were included from seven European RA quality registries: ATTRA (Anti-TNF Therapy in Rheumatoid Arthritis [Czech Republic]), DANBIO (Danish Rheumatologic Database), ROB-FIN (National Registry of Antirheumatic and Biological Treatment in Finland), ORA (Orencia and Rheumatoid Arthritis [France]), GISEA (Italian Group for the Study of Early Arthritis), BIOBADASER (Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases), and the SCQM (Swiss Clinical Quality Management) system. Each registry is unique with respect to design, data collection, definition of the study cohort, reporting, and validation of outcomes. In general, registries defined the index date as the first day of abatacept treatment and reported data for infections requiring hospitalization and overall malignancies; data for other infection and malignancy outcomes were not available for every cohort. Abatacept exposure was measured in patient-years (p-y). Incidence rates (IRs) were calculated as the number of events per 1000 p-y of follow-up with 95% confidence intervals.ResultsOver 5000 patients with RA treated with abatacept were included. Most patients (78–85%) were female, and the mean age range was 52–58 years. Baseline characteristics were largely consistent across registries. Among patients treated with abatacept, IRs for infections requiring hospitalization across the registries ranged from 4 to 100 events per 1000 p-y, while IRs for overall malignancy ranged from 3 to 19 per 1000 p-y.ConclusionsDespite heterogeneity between registries in terms of design, data collection, and ascertainment of safety outcomes, as well as the possibility of under-reporting of adverse events in observational studies, the safety profile of abatacept reported here was largely consistent with previous findings in patients with RA treated with abatacept, with no new or increased risks of infection or malignancy.

Characteristics of Late-Onset Spondyloarthritis: Data from the Moroccan Registry of Biological Therapies in Rheumatic Diseases.

Introduction The Assessment of SpondyloArthritis InternationalSociety (ASAS) criteria for axial and peripheral spondyloarthritis (SpA) allow for the classification of patients with an age of onset of disease of less than 45 years. However, SpA can start after this age. This study aimed to assess the characteristics of late-onset SpA (SpA>45 years) in the Moroccan registry of biological therapies in rheumatic diseases (RBSMR). Methods A cross-sectional study was conducted using the baseline data of the RBSMR.The protocol for the original RBSMR study was reviewed and approved by the Ethics Committee for Biomedical Research Mohammed V University - Rabat, Faculty of Medicine and Pharmacy of Rabat (approval number for the study was 958/09/19, and the date of approval was September 11, 2019), and all patients had given their written consent. Patients who met the 2009 ASAS criteria for SpA were included. They were divided into two groups: early-onset SpA (≤ 45 years) and late-onset SpA (>45 years). Clinical, biological, radiological, and therapy data of the two groups were compared.Statistical analysis was performed using SPSS v25 software (IBM Corp. Armonk, NY).Parameters with a p-value ≤0.05 were considered significant. Results Our population consisted of 194 patients. Thirty-one patients (16%) had late-onset SpA. Comparison between patients with early-onset (≤45 years) and late-onset SpA(>45 years) revealed that late-onset SpA had a higher tender joint count (p=0.01), a higher swollen joint count (p=0.02), depression (p=0.00), fibromyalgia (p=0.001), hypercholesterolemia (p=0.01), and a lower frequency of coxitis (p=0.008). Logistic regression analysis confirmed that late-onset SpA was associated with a higher tender joint count (OR=0.93, CI 95%: 0.88-0.98), a higher swollen joint count (OR=0.92, CI 95%: 0.85-0.99), depression ( OR=0.19, CI 95%:0.04-0.38), fibromyalgia (OR=1.75, CI 95%: 1.74-17.85), and a lower frequency of coxitis ( OR=0.29,CI 95%: 0.11-0.75). Conclusion As life expectancy increases, late-onset SpA will become increasingly common. It is therefore imperative to determine its characteristics. In the RBSMR study, late-onset SpA was associated with a high number of tender and swollen joints, depression, fibromyalgia, and a lower frequency of coxitis.

6) Targeted Therapy in Rheumatic Diseases

6) Targeted Therapy in Rheumatic Diseases

Koebner’s phenomena observed in patient receiving adalimumab in psoriasis

Koebner’s phenomena, first described in 1877 as the appearance of psoriatic lesions in the uninvolved skin of psoriatic patients as a consequence of trauma. Koebner phenomena has been associated with the use of biological response modifiers. The development of the anti-TNF therapies is a milestone in the therapy of rheumatic diseases. As in all new treatment opportunities it is of concern whether all potential undesired side effects have been evaluated. We report a case involving a 31-year-old young male patient diagnosed with psoriasis and psoriatic arthritis (PsA) since a year, who received Adalimumab as part of his treatment and developed Koebner’s phenomena.

Evaluation of the effectiveness of intra-articular injections of glucocorticoids in knee synovitis in patients with rheumatic diseases in real clinical practice

Intra-articular injections of glucocorticoids are widely used in the complex therapy of rheumatic diseases (RD). However, there is insufficient data on their effectiveness and safety in real clinical practice.The aim of the study – to evaluate the effectiveness of intra-articular injections of glucocorticoids in rheumatic diseases in real clinical practice.Material and methods. The study group consisted of 290 patients with RD, mainly osteoarthritis (OA) and rheumatoid arthritis (RA) (69.0% – women; age – 55.6±12.6 years), who underwent intra-articular injections of glucocorticoids in the knee joint. Indications for intra-articular injections of glucocorticoids were determined by the attending physicians. The control group consisted of 112 patients with OA (71.4% – women; age 59.3±14.6 years) who underwent a course of intra-articular injections of hyaluronic acid. The result of treatment was evaluated in 2 weeks, 1 and 3 months according to a telephone survey.Result. After 2 weeks, 1 month and 3 months after the intra-articular injections of glucocorticoids, the severity of pain during movement decreased (numerical rating scale (NRS) 0–10; Me [25%; 75%]) from 6.0 [4.0; 8.0] to 1,0 [0; 2,0], 2,0 [1,0; 4,0] and 2.5 [1.0; 4.0] respectively (p&lt;0.001). After 3 months, the number of patients with no pain or mild pain (&lt;4 NRS) was 63.8%, with complete/almost complete absence of pain (≤1 NRS) – 30.3%. The effect of intraarticular injections of glucocorticoids was higher in RA than in OA: pain dynamics after 3 months –4.0 [–2.0; –6.0] and –2.0 [–1.0; –5.0] respectively (p=0.003). In OA, the effect of intra-articular injections of glucocorticoids and of hyaluronic acid did not differ: the dynamics of pain after 3 months was –2.0 [–1.0; –5.0] and –3.0 [–1.0; –5.0] respectively (p=0.869). No serious adverse reactions were noted at intra-articular injections of glucocorticoids.Conclusions. Intra-articular injections of glucocorticoids are an effective and fairly safe method of short-term treatment of synovitis in rheumatic diseases.

6) Targeted Therapy in Rheumatic Diseases

6) Targeted Therapy in Rheumatic Diseases

Urotoxicity and safety data of low-dose intravenous cyclophosphamide therapy for rheumatic diseases: A Single-Center retrospective cohort study

Despite its effectiveness in rheumatic diseases, cyclophosphamide (CYC) treatment should be used with caution due to its side effects. CYC is thought to pose a risk in the development of hemorrhagic cystitis and bladder cancer. This study aims to determine the incidence of hemorrhagic cystitis and bladder cancer with intravenous low-dose CYC therapy used in the treatment of rheumatic diseases. A total of 211 adult patients with rheumatic disease treated with intravenous CYC were evaluated in this retrospective study conducted between January 2006 and May 2021. Patient data including cumulative CYC dose, treatment frequency, duration of treatment, side effects, such as hemorrhagic cystitis and bladder cancer were acquired from medical archives. The mean follow-up period was 48.5 (3–180) months, and the mean cumulative CYC dose was 5g (2–19g). None of the patients received mesna therapy concurrent with CYC therapy. 11 patients developed hemorrhagic cystitis (5.2%). Hemorrhagic cystitis was found to be statistically significantly associated with the number of CYC cycles (p=0.04). All patients were asymptomatic. No statistically significant difference was observed between hemorrhagic cystitis, treatment duration, and cumulative dose for CYC therapy in rheumatic diseases. Malignancy developed in 12 patients (5.7%) after CYC treatment. Bladder cancer was observed in 1 patient. According to our findings, the only risk factor for hemorrhagic cystitis in patients receiving CYC was the number of CYC cycles. Intravenous CYC regimen did not cause symptomatic hemorrhagic cystitis. Low-dose IV CYC may be safe in terms of serious urotoxic side effects when used at the appropriate dose, duration and frequency.

Gut Microbiota-Medication Interaction in Rheumatic Diseases.

Besides its contribution to the development of rheumatic diseases, the gut microbiota interact with anti-rheumatic drugs. The intestinal microbiota can directly metabolize many drugs and indirectly change drug metabolism through a complex multi-dimensional interaction with the host, thus affecting individual response to drug therapy and adverse effects. The focus of the current review is to address recent advances and important progress in our understanding of how the gut microbiota interact with anti-rheumatic drugs and provide perspectives on promoting precision treatment, drug discovery, and better therapy for rheumatic diseases.

Cost-Effectiveness of Therapeutic Drug Monitoring-Guided Adalimumab Therapy in Rheumatic Diseases: A Prospective, Pragmatic Trial.

IntroductionTo assess the clinical and cost-effectiveness of therapeutic drug monitoring (TDM) based on serum adalimumab levels compared to standard of care in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. MethodsThis was a non-inferiority, multicentric, non-randomized, pragmatic trial including adult patients diagnosed with moderate-to-severe, clinically stable rheumatic diseases treated with adalimumab. Consecutive patients were assigned 1:2 to the control (CG) or the intervention group (IG), based on the site of inclusion, and followed up for 18 months. Adalimumab serum levels were measured at each study visit and released to the IG only to modify dosing strategy. Data on disease activity, healthcare resource utilization and health-related quality of life (HRQoL) measured through the EQ-5D-5L were collected. Number of persistent and overall flares, time to first flare, days experiencing high disease activity, total direct costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated.ResultsOf the 169 recruited patients, 150 were included in the analysis (52 and 98 patients in the CG and IG, respectively). The primary endpoint was not met as persistent flares were not significantly lower in the IG, although mean (SD) number of flares was numerically lower in the IG (0.67 [0.70] versus 0.90 [0.82], P = 0.073), respectively. Based on EQ-5D-5L utilities, HRQoL was significantly higher in the IG at 3 (P = 0.001) and 6 months (P = 0.035), which overall translated into 0.075 QALYs gained per patient for the IG at month 18. Overall, direct costs were significantly lower for the IG patients (€15,311.59 [4,870.04] versus €17,378.46 [6,556.51], P = 0.030), resulting in the intervention being dominant, leading to increased QALY at a lower overall costConclusionAdalimumab dose tapering based on TDM for rheumatic patients led to an increased quality of life and QALY gain and entailed lower costs, being a more cost-effective alternative than clinically guided management.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00345-5.

Uncharted waters: mesenchymal stem cell treatment for pediatric refractory rheumatic diseases; a single center case series

BackgroundWith the advent of innovative therapies including biologics and Janus kinase inhibitors, children with rheumatic diseases are more likely to have improved outcomes. Despite these advances, some children do not respond, or they, or their parents fear adverse events and seek other alternatives. Increasingly, private companies are offering mesenchymal stem cells (MSC) as an alternative, which are described as natural therapies for rheumatic diseases, often insinuating them as a cure. MSC have immunomodulatory properties, and transplantation of these stem cells have been used to successfully treat immunologic conditions like graft-versus-host disease. Lately, MSC research in adult lupus has been encouraging, but the clinical trials are still underway and in most, MSC therapy is not a standalone treatment. This retrospective case series will highlight three cases of pediatric refractory autoimmune disease whose parents sought out and received MSC therapy as a self-decision without first seeking medical advice from our specialty. The three families felt that their children were improved and in two believed that their child was cured. MSC have the potential of beneficial immunomodulation and may be a powerful tool in the therapy of rheumatic disease, but well controlled clinical trials are necessary and should be designed and monitored by experts in childhood rheumatic disease.Case presentationThree children with three different rheumatic diseases; systemic lupus erythematosus, mixed connective tissue disease and juvenile idiopathic arthritis were under the care of pediatric rheumatology at a large, tertiary-care, teaching institution. Multiple non-biologic and biologic disease-modifying anti-rheumatic drugs failed to significantly decrease disease activity, and as a result, the families chose to undergo MSC therapy. After transplantation, all children improved per patient and parent report and tapered off conventional immunosuppressive drugs. No serious adverse events occurred in these three patients.ConclusionThe three cases presented in this report reflect comparable beneficial outcomes and minimal risks published in adult studies. These were not controlled studies, however, and benefit was reported rather than documented. These cases suggest that MSC transplantation may prove a promising adjunctive treatment option; however, further research, development of standardized infusion therapy protocols, and well-designed monitored clinical trials are essential.

Inflammation-targeted therapies and cancer

To review and analyze the current knowledge on the risk of malignancy associated with inflammation-targeted therapies in rheumatic diseases. We performed a non-systematic literature review on PubMEd MEDLINE by screening randomized controlled trials, meta-analyses, reviews, and observational studies focusing on malignancies and inflammation-targeted therapies including TNF inhibitors, other biologics and JAK inhibitors in rheumatic diseases. Data from literature are reassuring regarding the overall risk of incident and recurrent cancer with TNF inhibitors. The risk of lymphoma is more difficult to analyze and data are controversial; however, in most of the studies, this risk does not seem to be significanlty increased. By contrast, there is probably an increased risk of non-melanoma skin cancer associated with TNF inhibitors, as with other immunosuppressants. There is no signal for an increased risk of malignancies with other biological DMARDs, but additional data are needed. A recent post-marketing surveillance study found out an increased risk of malignancies for tofacitinib compared with TNFi; additional data are, therefore, urgently needed to confirm or not these results. Data are presently reassuring regarding the overall risk of cancer, whatever the inflammation-targeted treatment. However, additional data are needed for non-TNF biologics and JAK-inhibitors.

Reduction of Pneumocystis jirovecii pneumonia and bloodstream infections by trimethoprim–sulfamethoxazole prophylaxis in patients with rheumatic diseases

Objective: Trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is routinely administered to patients with rheumatic diseases in Japan. The present study aimed to evaluate the effect of TMP/SMX prophylaxis on PJP and non-central line-associated bloodstream infections (BSIs) in patients receiving high-dose glucocorticoids for the treatment of rheumatic diseases. Method: This study enrolled patients who were admitted between 1 October 2003 and 31 March 2018 and began high-dose glucocorticoid therapy for rheumatic diseases during hospitalization. The observation period was 4 months from the commencement of high-dose glucocorticoid therapy. The effect of TMP/SMX prophylaxis on PJP and non-central line-associated BSI was analysed. Results: Of the 437 patients included in the study, 376 received TMP/SMX prophylaxis and 61 patients did not. During the observation period, TMP/SMX prophylaxis was discontinued in 76 patients (20.2%). Three PJP cases (0.7%) occurred. Among the 399 patients included in our analysis of non-central line-associated BSI, eight experienced non-central line-associated BSI (2.0%). Among the covariates, TMP/SMX prophylaxis was associated with reduced PJP and non-central line-associated BSI incidence [odds ratio (OR) 0, 95% confidence interval (CI) 0.00–0.38, and OR 0.08, 95% CI 0.01–0.42, respectively]. Conclusion: Routine TMP/SMX prophylaxis reduced the incidence of both PJP and BSI in patients with rheumatic diseases undergoing high-dose glucocorticoid therapy.

One-year direct costs of biological therapy in rheumatoid arthritis and its predictive factors: data from the Moroccan RBSMR registry.

The aim of the study was to estimate the annual direct costs of biological therapies in rheumatoid arthritis (RA), and to establish possible factors associated with those costs. The main data source was the Moroccan registry of biological therapies in rheumatic diseases (RBSMR Registry). We included patients with available 1-year data. Variables related to socio-economic status, disease and biological therapy were collected. Direct costs included prices of biologics, costs of infusions, and subcutaneous injections. Differences in costs across groups were tested by Mann-Whitney and Kruskal-Wallis tests. Correlations analysis was performed in search of factors associated with high costs. We included 197 rheumatoid arthritis patients. The mean age was 52.3 ± 11years, with female predominance 86.8%. Receiving one of the following therapies: rituximab (n = 132), tocilizumab (n = 37), or TNF-blockers (n = 28). Median one-year direct costs per patient were €1665 [€1472-€9879]. The total annual direct costs were € 978,494. Rituximab, constituted 25.7% of the total annual budget. TNF-blockers and tocilizumab represented 27.3% and 47% of this overall budget, respectively. Although the costs were not significantly different in terms of gender or level of study, the insurance type significantly affected the cost estimation. A positive correlation was found between the annual direct cost and body mass index (r = 0.15, p = 0.04). In Morocco, a developing country, the annual direct costs of biological therapy are high. Our results may contribute to the development of strategies for better governance of these costs.

The safety of nonsteroidal anti-inflammatory drugs in population-based studies: the benefits of aceclofenac

Effective pain relief in rheumatology practice is one of the most important criteria for the quality of medical care. Therefore, drugs with analgesic effects, primarily nonsteroidal anti-inflammatory drugs (NSAIDs), are among the most commonly used ones in the combination therapy of rheumatic diseases. All NSAIDs are capable of causing to one degree or another extent unwanted reactions that occur in the gastrointestinal tract (GIT), cardiovascular system (CVS), liver, kidneys, and allergic reactions. Considering the widespread use of NSAIDs, the problem of preventing these complications becomes not only medical, but also social. In 2008, the European Union launched the international project SOS (Safety Of non-Steroidal anti-inflammatory drugs) to study the safety of NSAIDs. The results of this project have shown that aceclofenac is one of the most successful drugs in combining the safety for GIT and CVS. Compared with other NSAIDs, this drug has a minimal risk for GI bleeding (relative risk (RR) 1.43; 95% confidence interval (CI), 0.65–3.15); it does not increase the risk of hospitalization for heart failure (RR, 1.03; 95% CI, 0.91–1.15) or the risk of developing myocardial infarction (RR 1.04; 95% CI, 0.90–1.19) either. The risk of ischemic stroke during aceclofenac therapy was slightly increased (RR, 1.17); but statistically insignificant (95% CI, 0.98–1.39). A large number of randomized clinical trials, meta-analyses, and observational programs have demonstrated that aceclofenac has pronounced analgesic and anti-inflammatory effects that are comparable to those of other NSAIDs and can be used in diseases accompanied by musculoskeletal pain, including that in older patients.

Problems of biological therapy for rheumatic diseases

Problems of biological therapy for rheumatic diseases

Cell technologies in the treatment of rheumatic diseases

Rheumatic diseases are caused by chronic autoimmune processes that require long-term therapy, which leads to the formation of resistance to the drugs used. The search for new approaches to their treatment in recent years has been enriched with the use of cell therapy methods. They are considered in this review of the literature and include the transplantation of hematopoietic stem cells, mesenchymal stem (stromal) cells, the induction or administration of T-regulatory cells, tolerogenic dendritic cells. The paper discusses methods of obtaining cell products, their safety and clinical use in patients with systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and other rheumatic diseases, and treatment complications. Based on the analysis, the authors give the comparative characteristics of various types of tolerogenic cell therapy for rheumatic diseases and point out their advantages, disadvantages, and the specific features of clinical application.

Cannabis-Based Medicines and Medical Cannabis in Rheumatic Diseases: A Treasure Chest or Pandora’s box

Interest in cannabinoids as a therapy in rheumatic diseases has grown exponentially. With legalization of medical and recreational cannabis in many jurisdictions worldwide, patients have easier access and opportunity to explore medicinal use. We report on the evidence for effect of cannabinoids in rheumatic diseases and critically address the current challenges surrounding use. Preclinical study of cannabinoids points to an effect on pain and inflammation, fundamental features of rheumatic diseases. The findings of the few randomized controlled trials (RCTSs) of cannabis-based medicines in rheumatic diseases are limited by short study duration, small study samples, and methodology flaws. There are no RCTs of medical cannabis in rheumatic diseases. Therefore, current guidelines mostly recommend against use of any cannabinoid product for rheumatology patients. Even with limited clinical evidence, patients are increasingly showing interest in cannabis. Rheumatologists must be diligent in exploring other established treatment options prior to a trial of cannabinoids in any form. Cannabis holds potential as a treasure chest for rheumatic disease treatment, but with true effect and risks largely unknown and requiring study. Governments’ move to legalize medical cannabis has bypassed the established procedures of drug approval and opened Pandora’s box.

Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors

The safety profile of interleukin (IL) inhibitors is not well established. To assess the risk of serious infections, opportunistic infections, and cancer in patients with rheumatologic diseases treated with IL inhibitors. Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations; Ovid MEDLINE Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus were searched (inception to November 30, 2018). Randomized, placebo-controlled trials that evaluated IL inhibitor therapies in rheumatic diseases and reported safety data were included in the analyses. This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Two investigators independently extracted study data and assessed risk of bias and certainty in the evidence. Fixed-effects meta-analysis was conducted to pool odds ratios (ORs) for serious infections, opportunistic infections, and cancers for IL inhibitors vs placebo. The outcomes of interest were the number of serious infections, opportunistic infections, and cancers in individuals receiving IL inhibitor therapies compared with placebo. In this meta-analysis, 74 studies comprising 29 214 patients (24 236 patients for serious infections, 9998 for opportunistic infections, and 21 065 for cancer [number of patients overlaps for each outcome]) were included. Patients receiving IL inhibitors had a higher risk of serious infections (OR, 1.97; 95% CI, 1.58-2.44; P < .001, I2 = 0%; high certainty), opportunistic infections (OR, 2.35; 95% CI, 1.09-5.05; P = .03, I2 = 0%; moderate certainty), and cancer (OR, 1.52; 95% CI, 1.05-2.19; P = .03, I2 = 11%; moderate certainty). The risk of serious infections, opportunistic infections, and cancer appears to be increased in patients with rheumatologic diseases who are treated with IL inhibitors compared with placebo.