ANTECEDENTES:

El golimumab es un inhibidor humanizado del factor de necrosis tumoral alfa, recientemente aprobado por la Food and Drug Administration (FDA) para el tratamiento de la artritis reumatoide (AR).

OBJETIVOS:

El objetivo de esta revisión sistemática fue comparar la eficacia y la seguridad del golimumab (sólo o en combinación con FARME o productos biológicos) con placebo (sólo o en combinación con FARME o productos biológicos), en ensayos clínicos aleatorios o cuasialeatorios en adultos con AR.

ESTRATEGIA DE BÚSQUEDA:

Un bibliotecario experto buscó en seis bases de datos cualquier ensayo clínico de golimumab para la AR, incluidas las bases de datos Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL), OVID MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) y Current Controlled Trials.

CRITERIOS DE SELECCIÓN:

Los estudios se incluyeron si utilizaron golimumab en adultos con AR, eran aleatorios o cuasialeatorios y si proporcionaron resultados clínicos.

OBTENCIÓN Y ANÁLISIS DE LOS DATOS:

Dos revisores (JS, SN) examinaron de forma independiente todos los títulos y resúmenes, seleccionaron los estudios apropiados para una revisión completa y examinaron el texto completo de los artículos para la selección final de los estudios incluidos. Para cada estudio, se extrajeron de forma independiente las características del estudio, los datos de seguridad y eficacia y se realizó una evaluación del riesgo de sesgo. Las discrepancias se resolvieron mediante consenso. Para las medidas continuas, se calcularon las diferencias de medias o las diferencias de medias estandarizadas y para las medidas categóricas, se calcularon los riesgos relativos. Se calcularon los intervalos de confianza del 95%.

RESULTADOS PRINCIPALES:

Se incluyeron cuatro ECA con 1231 pacientes tratados con golimumab y 483 pacientes tratados con placebo. De estos pacientes, 436 recibieron tratamiento con la dosis de golimumab aprobada por la FDA, 50 mg cada cuatro semanas. En comparación con los pacientes tratados con placebo+metotrexato, los pacientes tratados con la dosis aprobada por la FDA de golimumab+metotrexato tuvieron 2,6 veces más probabilidades de alcanzar el ACR50 (intervalo de confianza [IC] del 95%: 1,3 a 4,9; p = 0,005 y NNT = 5; intervalo de confianza del 95%: 2 a 20), no fue más probable que presentaran eventos adversos (riesgo relativo 1,1; IC del 95%: 0,9 a 1,2; p = 0,44) y tuvieron 0,5 veces más probabilidades de tener retiros generales (IC del 95%: 0,3 a 0,8; P = 0,005). Los pacientes tratados con golimumab tuvieron significativamente más probabilidades de lograr la remisión, disminuir la actividad de la enfermedad y mejorar la capacidad funcional en comparación con los tratados con placebo (todos los resultados fueron estadísticamente significativos). No se observaron diferencias significativas entre golimumab y placebo con respecto a eventos adversos graves, infecciones, infecciones graves, infecciones pulmonares, tuberculosis, cáncer, retiros debido a eventos adversos e ineficacia y muertes. No se informaron datos radiográficos.

CONCLUSIONES DE LOS AUTORES:

Con un grado general alto de pruebas, en la dosis aprobada por la FDA el golimumab es significativamente más eficaz que placebo en el tratamiento de pacientes con AR activa cuando se utiliza en combinación con el metotrexato. El perfil de seguridad a corto plazo, según los ECA a corto plazo, es razonable y no existen diferencias en los eventos adversos totales, las infecciones graves, el cáncer, la tuberculosis o las muertes. Se necesitan estudios de vigilancia a largo plazo para evaluar la seguridad.

Objective. To perform a Cochrane systematic review of benefit (American College of Rheumatology 50% improvement criteria; ACR50) and safety (adverse events and withdrawals) of golimumab in patients with rheumatoid arthritis (RA). Methods. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), OVID Medline, CINAHL, Embase, Science Citation Index (Web of Science), and Current Controlled Trials databases for randomized or controlled clinical trials of golimumab compared to placebo or disease-modifying antirheumatic drug in adults with RA. Two authors independently selected appropriate studies and abstracted study characteristics and safety and efficacy data and performed risk-ofbias assessment.We calculated mean differences for continuous measures, and relative risks for categorical measures. Results. Four randomized controlled trials with 1231 golimumab-treated and 483 placebo-treated patients were included. Of these, 436 were treated with golimumab at 50 mg every 4 weeks [a dosage approved by the US Food and DrugAdministration (FDA)]. At an average of 4-6 months, compared to patients treated with placebo and methotrexate (MTX), patients treated with the FDA-approved dosage of golimumab and MTX were 2.6 times more likely to reach ACR50 (p = 0.005, 95% CI 1.3, 4.9; absolute percentage, 38% vs 15%) and 0.5 times as likely to have overall withdrawals (p = 0.005, 95% CI 0.3, 0.8; absolute percentage, 5% vs 10%). Golimumab-treated patients were significantly more likely than those taking placebo to achieve remission (22% vs 4%; p < 0.00001), and to have improvement in functional ability on the Health Assessment questionnaire [0.2 points lower (p < 0.00001, 95% CI 0.25, 0.15); absolute risk difference, -20% (95% CI -25% to -15%); relative percentage difference, -11% (95% CI-14% to -8.3%)]. The studies were too small and short to be powered sufficiently for safety outcomes, but no substantive statistically significant differences were noted between golimumab and placebo regarding adverse events, serious adverse events, infections, serious infections, lung infections, tuberculosis, cancer, withdrawals due to adverse events, and withdrawals due to inefficacy and deaths. Conclusion. At the approved dosage, in patients with active RA taking background MTX, golimumab is significantly more beneficial than placebo. The short-term safety profile is reasonable. Longterm surveillance studies are needed for safety assessment. The Journal of Rheumatology Copyright © 2010. All rights reserved.

IMPORTANCE OF THE FIELD:

Twenty-five years ago, rheumatoid arthritis (RA) was a relentless disease, treated symptomatically because of the lack of effective, well tolerated medications which could halt disease in most patients. The introduction of methotrexate, sulfasalazine and leflunomide, and aggressive treatment, changed the prognosis of RA in the 1990s. Biologic therapies have dramatically changed the long-term prognosis of patients with rheumatoid and psoriatic arthritis and ankylosing spondylitis.

AREAS COVERED IN THIS REVIEW:

Unfortunately, no one single agent is fully effective in every patient. For this reason, another agent, golimumab (GLM), a TNF-alpha inhibitor (TNF-I) was developed. The basis of this review is all peer-reviewed manuscripts on GLM in the treatment of RA, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) found in Pub Med. and Medline from 2000 to 2010 and abstracts presented at the major rheumatology congresses within the past five years.

WHAT THE READER WILL GAIN:

This review describes the efficacy and safety of GLM and should enable an understanding of the benefit-risk profile of GLM in the treatment of RA, PsA and AS.

TAKE HOME MESSAGE:

GLM is effective and has a safety profile similar to other TNF-I in the treatment of RA, AS and PsA.

OBJECTIVE:

To evaluate the effects of golimumab on radiographic progression in patients with rheumatoid arthritis (RA).

METHODS:

Methotrexate (MTX)-naive patients (in the Golimumab Before Employing Methotrexate as theFirst-Line Option in the Treatment of Rheumatoid Arthritis of Early Onset [GO-BEFORE] study; n = 637)and patients with active RA despite MTX therapy (in the Golimumab in Active Rheumatoid Arthritis Despite Methotrexate Therapy [GO-FORWARD] study; n =444) were randomly assigned to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Golimumab orplacebo was administered subcutaneously every 4 weeks. Radiographs of the hands and feet were taken at baseline, week 28, and week 52 in the GO-BEFORE study and at baseline, week 24 (week 16 for patients who entered early escape), and week 52 in the GO-FORWARD study. Radiographs were scored by 2 independent readers in each study using the van der Heijde modification of the Sharp score.

RESULTS:

In the GO-BEFORE study, the mean ± SD changes in the modified Sharp score from base line to week 52 (control period) were 1.4 ± 4.6 in group 1, 1.3 ± 6.2 in group 2 (P = 0.266), 0.7 ± 5.2 in group 3 (P = 0.015), and 0.1 ± 1.8 in group 4 (P = 0.025). In the GO-FORWARD study, changes from baseline to week 24 (control period) were 0.6 ± 2.4 in group 1, 0.3 ± 1.6 in group 2 (P = 0.361), 0.6 ± 2.7 in group 3 (P = 0.953), and 0.2 ± 1.3 in group 4 (P = 0.293).

CONCLUSION:

Golimumab in combination with MTX inhibited radiographic progression significantly better than did MTX alone in the GO-BEFORE study. Radiographic progression in the GO-FORWARD study was minimal in all treatment arms, precluding an adequate assessment of the effect of golimumab on radiographic progression in this study.

Golimumab is a fully human anti-TNF-alpha blocker that has demonstrated its efficacy in the treatment of numerous kinds of diseases. Although it is generally safe and well tolerated, various adverse events have been reported. The present aim is to improve the understanding of dermatologic adverse events associated with golimumab following a search of various scientific databases. This systematic review and meta-analysis shows that golimumab is associated neither with severe injection-site reactions nor with injection-site erythema. We found no significant lupus-like syndromes, and no significant skin squamous cell carcinoma. We further suggest systematic dermatologic monitoring in clinical practice during golimumab therapy. Subsequent research should employ a larger cohort of patients to ensure clear and significant future conclusions.

RECORD STATUS:

This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database.

CITATION:

Yang H, Epstein D, Bojke L, Craig D, Light K, Bruce I, Sculpher M, Woolacott N. Golimumab for the treatment of psoriatic arthritis. Health Technology Assessment 2011; 15(Suppl 1 Article 10): 87-96

RECORD STATUS:

None

CITATION:

National Institute for Health and Clinical Excellence. Golimumab for the treatment of psoriatic arthritis. London: National Institute for Health and Clinical Excellence (NICE). Technology Appraisal Guidance 220. 2011

RECORD STATUS:

None

CITATION:

Golimumab for the treatment of ankylosing spondylitis.. NIHR Health Technology Assessment programme.

As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the Evidence Review Group (ERG) produced a report to comment on the clinical and cost effectiveness of golimumab (Simponi(®), Merck Sharp & Dohme) for the treatment of ankylosing spondylitis (AS) relative to other comparators as presented in the manufacturer's submission (MS) to NICE. The population was those with active disease who had not responded to conventional therapy. The specified comparators were conventional care and two other tumour necrosis factor alpha (TNF-α) inhibitors (adalimumab and etanercept). Outcomes to be considered were disease activity, functional capacity, disease progression, adverse effects of treatment and health-related quality of life (HR-QOL). There were no head-to-head trials comparing TNF-α inhibitors. The submission included one trial of golimumab versus placebo (the GO-RAISE trial) and additionally seven placebo-controlled randomized controlled trials (RCTs) of other TNF-α inhibitor agents (five with etanercept, and two with adalimumab). The results of these trials were generally a statistically significant improvement from each of the TNF-α inhibitors. A Bayesian mixed treatment comparison (MTC) showed there was generally overlap in the 95 % credible intervals (CrIs) between the TNF-α inhibitors. Exceptions included a greater risk of discontinuation of treatment for golimumab than for etanercept (relative risk [RR] 4.30; 95 % CrI 1.01-18.50). The cost-effectiveness analysis (CEA) compared all of these TNF-α inhibitors. Relative effectiveness was informed only by RR of response (proportion achieving at least a 50 % improvement in Bath AS Disease Activity Index [BASDAI] score; BASDAI50) from the MTC. In the base-case analysis, the incremental cost-effectiveness ratio (ICER) of golimumab versus conventional care was £26,597 and adalimumab and etanercept were extendedly dominated by golimumab. The manufacturer concluded that golimumab is a cost-effective treatment option. Generally, the ERG agreed with the MTC analyses. The main problem was that the MS used data from one trial, which included a period of cross-over. The ERG found some problems with the CEA model, mainly that it did not allow for comparison of TNF-α inhibitor sequences and did not use MTC estimates for treatment discontinuation or adverse events (AEs). The ERG could not correct the sequencing problem, but re-ran the CEA with discontinuations and AEs estimated from the MTC and using the correct trial data. The results of the ERG analysis were that golimumab was extendedly dominated by etanercept, and the preferred treatment was either conventional treatment or etanercept, depending on the ICER threshold. Uncertainty was also substantial. NICE issued guidance (technology appraisal [TA] 233), which recommended golimumab according to the indications described in TA143 for etanercept and adalimumab, i.e. as first-line therapy among the TNF-α inhibitors unless patients are intolerant to one or both alternatives. Given the factors cited by NICE for their decision, the ERG recommends that there should be greater clarity in the NICE methods guidance on handling uncertainty in CEAs as well as the incorporation of benefit from process of care.

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