Tumor-induced osteomalacia: A systematic literature review.

Introduction: Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor. Material and methods: We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online. Results: We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively. Conclusion: TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.

Gaps between research and recommendations in rheumatoid arthritis.

OBJECTIVES: To identify recommendations on the diagnosis and management of rheumatoid arthritis (RA) supported by low recommendation grades, to study the causes of this low grading, and to propose solutions. METHODS: A group of six rheumatologists, with extensive experience in the development of systematic reviews, reviewed national and international RA recommendations and practice guidelines. They identified all recommendations with a low level of evidence or recommendation grade (levels equivalent to 4, 5, or grades C or D of the Oxford Levels of Evidence), classified them by areas (diagnosis, follow-up, treatment, others), and analyzed plausible causes of low graduation. A Delphi was used to select 10 recommendations where it was most important to obtain quality evidence to support them. Subsequently, actions were proposed to improve evidence and recommendation grading. RESULTS: Fourteen documents were analyzed, in which 192 recommendations with low evidence/grade of recommendation were identified, most of which were on treatment. The two most frequent causes of this low level are the absence of studies and the discrepancy between the wording of the recommendation and the evidence used. Finally, the proposed solution to the critical recommendations is a list of unanswered research questions and possible designs to answer them. CONCLUSIONS: We propose to design and promote research that truly supports or rectifies clinical practice and, thus, bridges the gap between existing evidence and critical recommendations.

Risks of malignancies related to tofacitinib and biological drugs in rheumatoid arthritis: Systematic review, meta-analysis, and network meta-analysis.

OBJECTIVE: To summarize and compare the risks of malignancies accompanying biologic DMARDs (b-DMARDs) and tofacitinib in rheumatoid arthritis (RA) in randomized clinical trials (RCTs) and long-term extension studies (LTEs). METHODS: Articles in Medline, Embase, Cochrane Library, and the Web of Science dated from 2000 to February 2015. Selection criteria were as follows: (1) focus on RCTs or LTEs in RA; (2) treatment with b-DMARDs or tofacitinib; (3) data on malignancies; and (4) a minimum follow-up of 12 weeks. Data included publication details, study design, risk of bias, number and types of malignancies, and patient characteristics and treatments. DATA SYNTHESIS: Of 113 articles and one updated report that were meta-analyzed, overall malignancies in RCTs showed odds ratio (95% confidence intervals) of 1.01 (0.72, 1.42) for all TNF antagonists, 1.12 (0.33, 3.81) for abatacept, 0.54 (0.20, 1.50) for rituximab, 0.70 (0.20, 2.41) for tocilizumab, and 2.39 (0.50, 11.5) for tofacitinib. Network meta-analysis of overall malignancies showed odds ratio (95% predictive intervals) of 1.68 (0.48-5.92) for infliximab, 0.79 (0.44-1.40) for etanercept, 0.93 (0.43-2.03) for adalimumab, 0.87 (0.28-2.75) for certolizumab, 0.87 (0.39-1.95) for golimumab, 1.04 (0.32-3.32) for abatacept, 0.58 (0.21-1.56) for rituximab, 0.60 (0.16-2.28) for tocilizumab, and 1.15 (0.24-5.47) for tofacitinib. Marginal numerical differences in the incidence rate of solid and hematological malignancies and non-melanoma skin cancers appeared in LTEs. CONCLUSIONS: In RCTs, treatment of RA with b-DMARDs or tofacitinib does not increase the risk for malignancies. Generalizability of the differences in the rate of specific malignancies encountered in LTEs requires continuous pharmacovigilance of real-world patients.

Impact of treatment with TNF antagonists on total cholesterol in patients with ankylosing spondylitis and psoriatic arthritis.

The objective of the study was to analyze the impact of TNF antagonists (TNFa) on the total cholesterol and triglycerides on ankylosing spondylitis (AS) and psoriatic arthritis (PsA). In this single-centre observational study of AS and PsA patients, differences in triglyceride and total cholesterol levels and frequency of hypertriglyceridemia and hypercholesterolemia at 3 and 6 months were analysed in patients treated and not treated with TNFa. General estimation equations and linear regression analysis were used to investigate associations between disease activity and lipid levels and to identify predictors of change. One hundred fifty-seven patients treated, and 157 not treated with TNFa, were included in the study. A transient increase in cholesterol level from baseline to 3 months in TNFa-treated patients was the only statistically significant effect (P < 0.001). Persistent percentages of hypertriglyceridemia and hypercholesterolemia from baseline were significantly higher in not treated than in TNFa-treated patients (P = 0.009 and P = 0.001, respectively). Inverse associations between changes in cholesterol level and Bath Ankylosing Spondylitis Disease Activity Index (P = 0.011) and CRP (P < 0.001), but not Disease Activity Score in 28 Joints (P = 0.095) were found in the whole group. In AS and PsA patients treated with TNFa, mild and transient changes in cholesterol but not in triglyceride levels were associated with changes in disease activity.

Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases.

OBJECTIVES: To assess the proportion of RA patients who discontinued biologics in world registries and health care databases and to identify causes and predictors of discontinuation. METHODS: Medline, Embase, Cochrane Library and Web of Science electronic databases and ACR and EULAR meeting abstracts were used. The selection of studies from world registries and health care databases including RA patients treated with biologics was independently performed. Data extracted from articles and abstracts were combined using a random effects model. Meta-analyses of percentages and hazard ratios were used to assess discontinuation. RESULTS: Ninety-eight studies with >200 000 patients from 11 242 articles and 119 abstracts met the inclusion criteria. Overall discontinuation rates of TNF inhibitors at 0.5, 1, 2, 3 and 4 years were 21, 27, 37, 44 and 52%, respectively. Discontinuation of etanercept was significantly lower at 3 and 4 years (35% and 41%, respectively) than infliximab and adalimumab (46% and 52%, respectively). Predictors of time to discontinuation were etanercept [hazard ratios (HRs) 0.58 and 0.77 versus infliximab and adalimumab, respectively), concomitant use of DMARDs (HR 0.77), disease duration (HR 1.01) and female sex (HR 1.18). Studies from registries conducted after 2005 and from countries with lower biologics access showed higher percentages of discontinuation. Relevant data on abatacept and tocilizumab were missing. CONCLUSION: In RA, treatment with etanercept has a lower percentage of discontinuation than infliximab and adalimumab. Concomitant use of DMARDs, disease duration before treatment with a biologic and female sex predict time to discontinuation.

Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis.

OBJECTIVE: To identify predictors of response to tumor necrosis factor (TNF) antagonists in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: Systematic review and meta-analysis of clinical trials and observational studies based on a systematic search. Meta-analyses of similar observations were performed using random effects computing summary OR. Heterogeneity was tested using I(2), and risks of bias using funnel plots and the Egger test. Meta-regression was used to explore causes of heterogeneity. RESULTS: The electronic search captured 1340 references and 217 abstracts. 17 additional articles were identified after searching by hand. A total of 59 articles meet the purpose of the study and were reviewed. 37 articles (33 studies) included 6736 patients with AS and 23 articles (22 studies) included 4034 patients with PsA. 1 article included data on AS and PsA. Age (OR (95% CI) 0.91 (0.84 to 0.99), I(2)=84.1%), gender (1.57 (1.10 to 2.25), I(2)=0.0%), baseline BASDAI (1.31 (1.09 to 1.57), I(2)=0.0%), baseline BASFI (0.86 (0.79 to 0.93), I(2)=24.9%), baseline dichotomous C reactive protein (CRP) (2.14 (1.71 to 2.68), I(2)=22.3%) and human leucocyte antigen B27 (HLA-B27) (1.81 (1.35 to 2.42), I(2)=0.0%) predict BASDAI50 response in AS. No factor was identified as a source of heterogeneity. Only meta-analysis of baseline BASFI showed risk of publication bias (Egger test, p=0.004). Similar results were found for ASAS criteria response. No predictors of response were identified in PsA. CONCLUSIONS: Young age, male sex, high baseline BASDAI, low baseline BASFI, high baseline CRP and HLA-B27 predict better response to TNF antagonists in AS but not in PsA.

Predictors of response to TNF antagonists.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that involves synovial tissue and leads to joint destruction. There are currently 5 tumor necrosis factor (TNF) antagonists licensed for the treatment of RA. This review summarizes the predictors of response to TNF antagonists in RA. Demographic variables were found to predict response, although not consistently. The variables associated with poor clinical response were presence of radiographic joint erosions at baseline, poor functional capacity at baseline, presence of human antibodies against TNF chimeric antibodies, and increase in anti-DNA and antinuclear antibodies. In selected populations, polymorphisms of TNF, TNF receptor, and Fc γ receptor were related to clinical response. Expression of TNF and other inflammatory cytokines in synovial tissue was explored. The heterogeneity of study populations limits the generalizability of the results in most studies.

Lipid profile changes in patients with chronic inflammatory arthritis treated with biologic agents and tofacitinib in randomized clinical trials: a systematic review and meta-analysis.

OBJECTIVE: To analyze lipid changes in patients with rheumatoid arthritis (RA) and patients with spondyloarthritis (SpA) treated with biologic agents or tofacitinib in randomized clinical trials (RCTs). METHODS: A systematic literature search was performed, using the Medline, Embase, Cochrane Library, and Web of Knowledge databases. Meta-analyses were performed using random-effects models to assess changes in the percentage of patients with abnormal lipid values or in the mean percentage of increase in the cholesterol and triglycerides levels. RESULTS: Twenty-five of 4,527 identified articles met the inclusion criteria. Compared with RA patients treated with placebo, those treated with tocilizumab were more likely to have hypercholesterolemia (odds ratio [OR] 4.64; 95% confidence interval [95% CI] 2.71, 7.95 [P < 0.001]), increased levels of high-density lipoprotein (HDL) cholesterol (OR 2.25; 95% CI 1.14, 4.44 [P = 0.020]), and increased levels of low-density lipoprotein (LDL) cholesterol (OR 4.80; 95% CI 3.27, 7.05 [P < 0.001]); this was not observed in patients treated with tumor necrosis factor (TNF) antagonists (OR 1.54; 95% CI 0.90, 2.66 [P = 0.119]) or tofacitinib (OR 3.4; 95% CI 0.62, 18.55 [P = 0.158]). Among patients receiving tofacitinib 5 mg twice daily, the mean percentage of increases in the HDL cholesterol level (weighted mean difference [WMD] 13.00 mg/dl; 95% CI 12.08, 13.93 [P < 0.001]) and the LDL cholesterol level (WMD 11.20 mg/dl; 95% CI 10.08, 12.32 [P < 0.001]) were higher than those in the comparator groups. Among patients treated with tofacitinib 10 mg twice daily, the mean percentage of increases in the HDL cholesterol level (WMD 15.21 mg/dl; 95% CI 13.28, 17.14 [P < 0.001]) and the LDL cholesterol level (WMD 15.42 mg/dl; 95% CI 11.77, 19.06 [P < 0.001]) were also higher than those in the comparator groups. No data were available for RA treated with other biologic agents or for SpA. CONCLUSION: In patients with RA treated with tocilizumab or tofacitinib but not with TNF antagonists, moderate changes in lipids are observed. Whether these changes pertain to the control of inflammation or to the mechanism of action of the biologic agents or tofacitinib remains undetermined.

Nuevos tratamientos en artritis reumatoide / New therapies for rheumatoid arthritis

No disponible

Risk of tuberculosis in patients with chronic immune-mediated inflammatory diseases treated with biologics and tofacitinib: a systematic review and meta-analysis of randomized controlled trials and long-term extension studies.

OBJECTIVE: The aim of this study was to assess the risk of active tuberculosis (TB) in patients with immune-mediated inflammatory diseases treated with biologics and tofacitinib in randomized controlled trials (RCTs) and long-term extension (LTE) studies. METHODS: A systematic review of the English-language literature by was performed by searching the Medline, Embase, Cochrane and Web of Knowledge databases. The search strategy focused on synonyms of diseases, biologics and tofacitinib. Data from RCTs were combined to assess the rate of TB using a random effects model. The incidence rate (IR) of TB and its association with disease, location and treatment were assessed in LTE studies. RESULTS: The search captured 11 130 articles and abstracts. One-hundred RCTs (75 000 patients) and 63 LTE studies (80 774.45 patient-years) met the inclusion criteria. There were 31 TB cases with TNF inhibitors, 1 with abatacept and none with rituximab, tocilizumab, ustekinumab or tofacitinib. The odds ratio for TNF inhibitors was 1.92 (95% CI 0.91, 4.03, P = 0.085). In LTE studies, the IR of TB was >40/100 000 with tofacitinib and all biologics except rituximab. IR was higher in RA patients with anti-TNF monoclonal antibodies [307.71 (95% CI 184.79, 454.93)] than in those with rituximab [20.0 (95% CI 0.10, 60)] and etanercept [67.58 (95% CI 12.1, 163.94)] or AS, PsA and psoriasis with etanercept [60.01 (95% CI 3.6, 184.79)]. The IR of TB was higher in high-background TB areas. CONCLUSION: RCTs are not sensitive enough to assess the risk of reactivation of latent TB infection (LTBI). Disease, treatment and background TB rate are associated with different frequencies of active TB. The benefit/risk balance of preventing reactivation of LTBI in different backgrounds should be considered in clinical practice.

[New therapies for rheumatoid arthritis]. / Nuevos tratamientos en artritis reumatoide.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammation of the synovial membrane and progressive destruction of the articular cartilage and bone. Advances in the knowledge of disease pathogenesis allowed the identification of novel therapeutic targets such as tumor necrosis factor (TNF), interleukin (IL)-1, IL-6 or the system JAK/STAT phosphorylation. At present there are 5 TNF antagonists approved for RA. Tocilizumab blocks the pathway of IL-6 and is the only biological with proven efficacy in monotherapy. Rituximab modulates B cell response in RA. Abatacept provided new data on T cell involvement in the pathogenesis of RA. Tofacitinib is the first kinase inhibitor approved for this disease. Biologic drugs have proven efficacy, almost always in combination with methotrexate, and even halt radiographic progression. Monitoring infection is the main precaution in handling these patients.

Rheumatoid factor and response to TNF antagonists in rheumatoid arthritis: systematic review and meta-analysis of observational studies.

OBJECTIVE: To systematically analyze literature with the aim of examining whether rheumatoid factor (RF) is a predictor of response to tumor necrosis factor (TNF) antagonists in rheumatoid arthritis (RA). METHODS: A systematic review and meta-analysis of observational studies were conducted. All studies on the association of baseline RF (titer and/or status) and response to any TNF antagonists, or with enough information to estimate this association were included. Qualitative analysis and meta-analysis using random-effects approach by type of outcome response and RF test was performed. Risk of publication bias was also evaluated. RESULTS: The systematic review included 18 studies of 4163 identified articles, involving 5703 patients with homogeneous baseline characteristics. The most common outcome to assess response was European League Against Rheumatism (EULAR) response criteria, normally merging good and moderate categories as response. The weighted mean difference (WMD) of baseline IgM RF titer in meta-analysis was higher in the non-responders group [-101.58 (95% CI -156.58,-46.59) I2=0.0]. Combined odds ratios (ORs) of positive IgM RF, positive IgA RF, and positive IgG RF to achieve good/moderate response were 1.08 (0.80, 1.47), I2=40.9%; 0.83 (0.39, 1.73), I2=39.8%, and 1.30 (0.48, 3.51), I2=62.9%, respectively. We did not find an association between a positive IgM RF and EULAR good response or remission. CONCLUSIONS: This meta-analysis does not support baseline IgM RF titer as a predictor of response to TNF antagonists in RA. However, this conclusion is hampered by high heterogeneity in the studies included in this meta-analysis.

Observational study of optimization of biologic therapies in rheumatoid arthritis: a single-centre experience.

To analyse the effectiveness of optimization of biologics in rheumatoid arthritis (RA). It was a single-centre retrospective observational study from January 2009 to September 2012. The effectiveness of the optimization of TNF antagonists, tocilizumab and abatacept in RA was studied. Optimization included predefined dose down-titration and/or expansion of dose interval in early arthritis with sustained DAS28-ESR <2.6 and established arthritis with a sustained DAS28-ESR <3.2. Primary outcome was time to relapse defined as increase in DAS28-ESR greater than 20 % over baseline. Cox's regression analysis was performed to identify predictors of relapse. Sixty-four patients were included in the study. In the survival analysis, rates of relapse were 9.8 % at 6 months, 31.4 % at 12 months and 44.6 % at 18 months. Rates of patients with an increase in DAS28-ESR > 20 % and ≥1 inflamed joint at 6, 9 and 18 months were 1.6, 17.2 and 27.1 %, respectively. In relapsing patients, mean DAS28-ESR at relapse was 3.44 (2.94-4.79) and mean DAS28-ESR following the return to the prior dose of the biologic was 2.52 (1.42-3.21). No predictors of relapse were found in multivariate analysis. Optimization of the treatment with biologics in RA is an efficacious and safe treatment option.

Immunogenicity of monoclonal antibodies against tumor necrosis factor used in chronic immune-mediated Inflammatory conditions: systematic review and meta-analysis.

IMPORTANCE: Knowledge of the immunogenicity of biologic agents may be helpful for the development of strategies for treatment of chronic immune-mediated inflammatory diseases. OBJECTIVE: To summarize the influence of antibodies against biologic agents (AABs [seropositivity]) on efficacy and safety in immune-mediated inflammatory diseases. DATA SOURCES MEDLINE, EMBASE, Cochrane Library, and the Web of Knowledge were searched for articles published in English, Spanish, French, Italian, or Portuguese between 2000 and March 2012. The search strategy focused on synonyms of diseases, immunogenicity, and biologic agents. Abstracts from 2001 to 2011 of the European League Against Rheumatism and American College of Rheumatology congresses were also included. STUDY SELECTION: The selection criteria were (1) observational or interventional studies in rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, spondyloarthritis, and psoriasis; (2) studies including patients who received biologic agents; and (3) studies collecting data on AABs. DATA EXTRACTION AND SYNTHESIS: Data collected included publication details, study design, characteristics of patients and treatments, presence of antibodies, and definition of response. MAIN OUTCOMES AND MEASURES: The primary end point was the association of AABs with response to treatment. Secondary end points were the association of AABs with safety, the association of AABs with concentration of the drug, and the influence of use of concomitant immunosuppressive therapy in the formation of AABs. RESULTS: The search captured 10 728 articles and abstracts. By hand and reverse search, 31 articles were additionally included. After evaluation of the full reports, 60 references were selected. They included 59 studies of anti-tumor necrosis factor monoclonal antibodies: 1 with etanercept, 2 with rituximab, and 2 with abatacept. In rheumatoid arthritis but not in inflammatory bowel disease or spondyloarthritis, seropositive patients presented worse clinical response at 6 months or less (odds ratio [OR], 0.03; 95% CI, 0.01-0.21), and at 6 months or more (0.03; 0.00-0.30) by meta-analysis. In rheumatoid arthritis, discontinuation of the biologic agent for all reasons was more common in seropositive patients (OR, 3.53; 95% CI, 1.60-7.82). In all conditions, seropositive patients had a higher risk of hypersensitivity reactions (OR, 3.97; 95% CI, 2.36-6.67). Overall, concomitant treatment with disease-modifying antirheumatic drugs, including azathioprine, decreased the risk of seropositivity (OR, 0.32; 95% CI, 0.25-0.42). CONCLUSIONS AND RELEVANCE: Presence of antibodies against anti-tumor necrosis factor monoclonal antibodies confers a risk of discontinuation of treatment in rheumatoid arthritis and a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases. The combined use of anti-tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks. Information on other biologic agents is fragmentary.

Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study.

OBJECTIVE: To compare the effectiveness of switching to rituximab (RTX) with switching to alternative tumour necrosis factor (TNF) antagonists in patients with rheumatoid arthritis (RA) failing on TNF antagonists. METHODS: A multicentre prospective 3-year observational study was performed in patients with RA treated with RTX or an alternative TNF antagonist. The baseline 28-joint disease activity score (DAS28) and Health Assessment Questionnaire (HAQ) score were compared with 6, 9 and 12 month values, adjusting for propensity score quintiles. Propensity scores were estimated for each patient using logistic regression with treatment as the dependent variable and baseline prior number of TNFs >1, years from diagnosis >5, extra-articular manifestations, previous toxicity, use of ≥2 disease-modifying antirheumatic drugs, age and sex as independent variables. RESULTS: 1124 patients were treated with either RTX (n=591, 52.6%) or alternative TNF antagonists (n=533, 47.4%). RTX-treated patients had longer disease duration (p=0.0001), larger numbers of previous TNF antagonists (p<0.0001) and tender and swollen joints (p<0.0001). There was no significant difference in the reduction in DAS28 at 6, 9 and 12 months between RTX-treated patients and those treated with TNF antagonists. However, the reduction in DAS28 was significantly different between RTX-treated patients and adalimumab/infliximab-treated patients (p=0.001 and p=0.05, respectively). There was a marginally significant difference at any time period in the proportion of patients achieving an improvement in the HAQ score of >0.22 (p=0.06). CONCLUSIONS: Optimal treatment for patients with RA failing on treatment with TNF antagonists may include RTX. This study suggests that the improvement in DAS28 is larger in patients treated with RTX than in those treated with monoclonal anti-TNF agents.

Efficacy and safety of TNF antagonists in sarcoidosis: data from the Spanish registry of biologics BIOBADASER and a systematic review.

OBJECTIVE: To evaluate the safety, efficacy, and effectiveness of TNF antagonists in patients with sarcoidosis. METHODS: A descriptive study of a case series registered in BIOBADASER and a systematic review was performed. The search strategy of articles published between 1998 and July 2011 in Medline, Embase, and the Cochrane Library included synonyms of sarcoidosis and synonyms of TNF antagonists. RESULTS: Seven patients treated with infliximab (IFX) and 1 with etanercept (ETN) switched to IFX for inefficacy were registered in BIOBADASER 2.0. In 3, treatment is still ongoing. Reasons for discontinuation were serious adverse events in 2 cases, inefficacy in 2 cases, and complete clinical response in 2 cases. Eight serious adverse events were reported. In the selected 69 of 2262 reports and 1 abstract of the review, 232 patients (89.9%) were treated with IFX and 26 (10.0%) were treated with ETN. In 2 randomized clinical trials, favorable response of the lung disease was reported with IFX. In other randomized clinical trials, no improvement of ocular manifestations was reported with ETN. In the cases series, results were diverse. Mean weighted rates of adverse events, infections, serious infections, and malignancy were 39.9, 22.1, 5.9, and 1.0 per 100 patient-years, respectively. CONCLUSIONS: There is insufficient evidence to ensure the efficacy of TNF antagonists in sarcoidosis. Nevertheless, IFX may be effective in selected manifestations of the disease. Before starting treatment of sarcoidosis with IFX, a careful evaluation of the benefit/risk ratio must be considered on an individual basis.