Matriz de evidencia
Inhibidores de TNF para artritis reumatoide
This matrix includes 89 Revisiones Sistemáticas Show Hide

Estudio primario

No clasificado

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study.

Año 2012
Revista Lupus
Enlaces DOI , Pubmed

Este artículo está incluido en 3 Revisiones sistemáticas Revisiones sistemáticas (3 referencias)

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OBJECTIVE:

This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus.

METHODS:

LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI score ≤ two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected.

RESULTS:

Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0 ± 15.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100 mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0-8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications.

CONCLUSION:

Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.

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Estudio primario

No clasificado

Double hit lymphoma: the MD Anderson Cancer Center clinical experience.

Año 2014
Revista British journal of haematology
Enlaces DOI , Pubmed

Este artículo no está incluido en ninguna revisión sistemática

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We report our experience with 129 cases of double hit lymphoma (DHL), defined as B-cell lymphoma with translocations and/or extra signals involving MYC plus BCL2 and/or BCL6. All cases were reviewed for histopathological classification. Median age was 62 years (range, 18-85), 84% of patients had advanced-stage disease, and 87% had an International Prognostic Index score ≥2. Fourteen patients (11%) had a history of low-grade follicular lymphoma. MYC translocation was present in 81%, and extra signals of MYC in 25% of patients. IGH-BCL2 translocation was present in 84% and extra signals of BCL2 in 12% of patients. Two-year event-free survival (EFS) rates in all patients and patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and R-HyperCVAD/MA (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate) were 33%, 25%, 67% and 32%, respectively. In patients achieving complete response with initial therapy (n = 71), 2-year EFS rates in patients who did (n = 23) or did not (n = 48) receive frontline stem cell transplantation were 68% and 53%, respectively (P = 0·155). The cumulative incidence of central nervous system involvement was 13% at 3 years. Multivariate analysis identified performance status ≥2 and bone marrow involvement as independent adverse prognostic factors for EFS and OS. Further research is needed to identify predictive and/or targetable biological markers and novel therapeutic approaches for DHL patients.

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Estudio primario

No clasificado

Pneumocystis jiroveci pneumonia in relation to CD4+ lymphocyte count in patients with B-cell non-Hodgkin lymphoma treated with chemotherapy.

Año 2010
Revista Leukemia & lymphoma
Enlaces DOI , Pubmed

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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An increasing incidence of Pneumocystis jiroveci pneumonia (PCP) in patients with B-cell non-Hodgkin lymphoma (B-NHL) receiving rituximab treatment has been reported. We reviewed patients with B-NHL who underwent chemotherapy from 2004 to 2008 at our institution to identify risk factors for PCP development during and after chemotherapy. Among 297 patients with B-NHL, six developed PCP. Of 121 patients (41%) who received PCP prophylaxis with sulfamethoxazole–trimethoprim during chemotherapy, none developed PCP (0%), while among 176 patients (59%) who had no prophylaxis, six (3.4%) developed PCP at a median of 2 months (range: 1–3 months) after starting chemotherapy. Patients with CD4+ lymphocyte counts ≤200/mm3 before chemotherapy had a higher risk of developing PCP (p=0.045), while a history of rituximab treatment was not related to PCP. CD4+ lymphocyte counts ≤200/mm3 during and after chemotherapy were observed in 18.9% of patients.

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Revisión sistemática

No clasificado

Treatment update of sensitized pediatric kidney transplant recipients: a review.

Año 2012
Autores Otukesh H , Hoseini R , Rahimzadeh N
Revista Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation
Enlaces DOI , Pubmed

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Sensitization of recipients is an increasing problem in children. Some case series in children exist comparing the diverse desensitizing protocols. These protocols include intravenous immunoglobulin, cytomegalovirus immune globulin, plasmapheresis, and some adjunctive therapies such as rituximab. Desensitizing protocols have advantages and disadvantages. Clinical trials are required to determine suitable protocols for sensitized pediatric recipients. We performed a systematic review of these protocols in children. A massive search was done in PubMed, Embase, and the Cochrane library system. The results of these studies are compared.

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Revisión sistemática

No clasificado

Effectiveness of biologic therapies for rheumatoid arthritis: an indirect comparisons approach.

Año 2011
Revista Pharmacotherapy
Enlaces DOI , Pubmed

Este artículo está incluido en 1 Síntesis amplia 32 Síntesis amplias (1 referencia)

Este artículo incluye 30 Estudios primarios 32 Estudios primarios (30 referencias)

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STUDY OBJECTIVE:

To compare the efficacy of biologic disease-modifying antirheumatic drugs (DMARDs) versus placebo with or without methotrexate, in treating rheumatoid arthritis.

DESIGN:

Comparative effectiveness analysis using an indirect treatment comparison (ITC) method in a Bayesian framework.

PATIENTS:

Adults with rheumatoid arthritis who had been enrolled in randomized controlled trials (RCTs) and had never failed biologic DMARD therapy.

MEASUREMENTS AND MAIN RESULTS:

Two random-effects logistic regression models, representing 6 and 12 months of treatment, were created using RCTs identified in a literature search. Twenty-three RCTs (11,589 patients) were included in the 6-month model and 10 RCTs (6051 patients) in the 12-month model. Nine biologic DMARDs in five therapeutic drug classes were included in the 6-month model, and six biologic DMARDs in three classes were included in the 12-month model. Our efficacy end point was the American College of Rheumatology 50% improvement criteria. In the 6-month model, all biologic DMARDs and methotrexate were significantly more efficacious than placebo and ranked in the following order: certolizumab (median log odds ratio [OR] 2.6), tocilizumab (1.7), rituximab (1.6), infliximab (1.6), etanercept (1.4), adalimumab (1.4), golimumab (1.4), abatacept (1.2), anakinra (1.0), and methotrexate (0.8). Of 45 pairwise comparisons, certolizumab was significantly more efficacious than methotrexate, but no other comparisons were significant. The rank order in the 12-month analysis was certolizumab (median log OR 2.0), rituximab (2.0), adalimumab (1.4), infliximab (1.4), etanercept (0.9), abatacept (0.6), and methotrexate (0.8). Of the 21 pairwise comparisons, none were significant. The results of the model using therapeutic class revealed that each class was more efficacious than placebo. In pairwise comparisons, each class was more efficacious than methotrexate, but none was more efficacious than another.

CONCLUSION:

Use of emerging ITC methods enabled us to compare the efficacy of biologic DMARDs for the treatment of rheumatoid arthritis in the absence of direct head-to-head comparison trials. Our methods enabled us to rank order these treatments. Further analyses by drug and by therapeutic class suggest that biologic DMARDs are similarly efficacious.

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Revisión sistemática

No clasificado

Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis.

Año 2017
Revista Rheumatology (Oxford, England)
Enlaces DOI , Pubmed

Este artículo incluye 117 Estudios primarios 117 Estudios primarios (117 referencias)

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OBJECTIVES:

To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA.

METHODS:

Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).

RESULTS:

A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI.: 1.18, 2.14), adalimumab (1.36, 95% CI.: 1.02, 1.81), etanercept (1.60, 95% CI.: 1.18, 2.17), golimumab (1.45, 95% CI.: 1.00, 2.08), rituximab (1.63, 95% CI.: 1.16, 2.30), tofacitinib (1.44, 95% CI.: 1.03, 2.02) and control (1.45, 95% CI.: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI.: 1.03, 1.65), etanercept (1.31, 95% CI.: 1.04, 1.67) and rituximab (1.34, 95% CI.: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates.

CONCLUSION:

Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs.

SYSTEMATIC REVIEW REGISTRATION NUMBER:

PROSPERO CRD42014014842.

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Revisión sistemática

No clasificado

High-dose therapy with autologous stem cell transplantation versus chemotherapy or immuno-chemotherapy for follicular lymphoma in adults.

Año 2012
Revista Cochrane database of systematic reviews (Online)
Enlaces DOI , Pubmed

Este artículo incluye 12 Estudios primarios 12 Estudios primarios (12 referencias)

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BACKGROUND:

Follicular lymphoma (FL) is the most common indolent and second most common Non-Hodgkin`s lymphoma (NHL) in the Western world. Standard treatment usually includes rituximab and chemotherapy. High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is an option for patients in advanced stages or for second-line therapy, leading to improved progression-free survival (PFS) rates. However, the impact of HDT and ASCT remains unclear, as there are hints of an increased risk of second cancers.

OBJECTIVES:

We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) comparing HDT plus ASCT with chemotherapy or immuno-chemotherapy in patients with FL with respect to overall survival (OS), PFS, treatment-related mortality (TRM), adverse events and secondary malignancies.

SEARCH METHODS:

We searched CENTRAL, MEDLINE, and EMBASE as well as conference proceedings from January 1985 to September 2011 for RCTs. Two review authors independently screened search results.

SELECTION CRITERIA:

Randomised controlled trials comparing chemotherapy or immuno-chemotherapy with HDT followed by ASCT in adults with previously untreated or relapsed FL.

DATA COLLECTION AND ANALYSIS:

We used hazard ratios (HR) as effect measures used for OS and PFS as well as relative risks for response rates. Two review authors independently extracted data and assessed the quality of trials.

MAIN RESULTS:

Our search strategies led to 3046 potentially relevant references. Of these, five RCTs involving 1093 patients were included; four trials in previously untreated patients and one trial in relapsed patients. Overall, the quality of the five trials is judged to be moderate. All trials were reported as randomised and judged to be open-label studies, because usually trials evaluating stem cell transplantation are not blinded. Due to the small number of studies in each analysis (four or less), the quantification of heterogeneity was not reliable and not evaluated in further detail. A potential source of bias are uncertainties in the HR calculation. For OS, the HR had to be calculated for three trials from survival curves, for PFS for two trials.We found a statistically significant increased PFS in previously untreated FL patients in the HDT + ASCT arm (HR = 0.42 (95% confidence interval (CI) 0.33 to 0.54; P < 0.00001). However, this effect is not transferred into a statistically significant OS advantage (HR = 0.97; 95% 0.76 to 1.24; P = 0.81). The subgroup of trials adding rituximab to both intervention arms (one trial) confirms these results and the trial had to be stopped early after an interim analysis due to a statistically significant PFS advantage in the HDT + ASCT arm (

PFS:

HR = 0.36; 95% CI 0.23 to 0.55; OS.: HR = 0.88; 95% CI 0.40 to 1.92). In the four trials in previously untreated patients there are no statistically significant differences between HDT + ASCT and the control-arm in terms of TRM (RR = 1.28; 95% CI 0.25 to 6.61; P = 0.77), secondary acute myeloid leukaemia/myelodysplastic syndromes (RR = 2.87; 95% CI 0.7 to 11.75; P = 0.14) or solid cancers (RR = 1.20; 95% CI 0.25 to 5.77; P = 0.82). Adverse events were rarely reported and were observed more frequently in patients undergoing HDT + ASCT (mostly infections and haematological toxicity).For patients with relapsed FL, there is some evidence (one trial, N = 70) that HDT + ASCT is advantageous in terms of PFS and OS (

PFS:

HR = 0.30; 95% CI 0.15 to 0.61; OS.: HR = 0.40; 95% CI 0.18 to 0.89). For this trial, no results were reported for TRM, adverse events or secondary cancers.

AUTHORS' CONCLUSIONS:

In summary, the currently available evidence suggests a strong PFS benefit for HDT + ASCT compared with chemotherapy or immuno-chemotherapy in previously untreated patients with FL. No statistically significant differences in terms of OS, TRM and secondary cancers were detected. These effects are confirmed in a subgroup analysis (one trial) adding rituximab to both treatment arms. Further trials evaluating this approach are needed to determine this effect more precisely in the era of rituximab. Moreover, longer follow-up data are necessary to find out whether the PFS advantage will translate into an OS advantage in previously untreated patients with FL.There is evidence that HDT + ASCT is advantageous in patients with relapsed FL.

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Síntesis amplia

No clasificado

Drug Class Review: Targeted Immune Modulators: Final Report Update 2

Año 2009
Libro Drug Class Reviews
Enlaces Pubmed

Este artículo incluye 216 Estudios primarios Estudios primarios (216 referencias) 25 Revisiones sistemáticas Revisiones sistemáticas (25 referencias)

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Targeted immune modulators, commonly referred to as biological response modifiers or simply biologics, are a relatively new category of medications used in the treatment of certain types of immunologic and inflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn’s disease, and ulcerative colitis. The US Food and Drug Administration approved the first of the biologics (infliximab) in 1998 and approved 9 additional agents since that time for treating various rheumatic conditions and plaque psoriasis: etanercept (1998), anakinra (2001), adalimumab (2002), alefacept (2003), efalizumab (2003), abatacept (2005), rituximab (2006), natalizumab (2008), and certolizumab pegol (2008). In this report, we review the comparative effectiveness, safety, and tolerability of targeted immune modulators.

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