Adalimumab, Etanercept, Infliximab and Golimumab for the Treatment of Ankylosing Spondylitis and Reactive Arthritis

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPPONI, A; MEGARELLI, C

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Ankylosing Spondylitis (AS) is the most common and characteristic disease of thespondyloarthropathy class. Its etiology is unknown and it affects the axial skeleton (sacroiliac jointsand spine) and ligaments. Up to 30 % of the patients may progress to ankylosis. The publishedincidence varies between 0.3 and 7.3 cases/100,000 people/year.Reactive arthritis (RA) is a non septic arthritis associated with an extraarticular infection whosemost common cause is a Chlamydia Trachomatis infection in 4-15% of the cases.The treatment goal for both conditions is to decrease the extent of inflammation to preserve theperformance status using NSAIDs and, in non responders, disease modifying drugs (DMDs) suchas sulfasalazine and methotrexate. The use of anti-TNF-alpha drugs for patients refractory to priorregimens has been proposed for AS and RA.TechnologyThe tumor necrosis factor-alpha (TNF-alpha) has inflammatory activity and is exacerbated inspondyloarthropathies. The anti-TNF-alpha is a recombinant human immunoglobulin which inhibitsits performance status, therefore the inflammatory activity and tissue damage decrease.Etarnercept is administered twice weekly; Adalimumab, weekly and Golimumab, monthly; the threeof them are subcutaneously administered. Infliximab is administered intravenously with additionaldoses on the second and sixth week and then every eight weeks.PurposeTo assess the available evidence on the efficacy, safety and coverage related issues on the use ofEtarnercept, Adalimumab, Infliximab and Golimumab in patients with ankylosing spondylitis andreactive arthritis.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internetgeneral search engines, in health technology evaluation agencies and health sponsors. Prioritywas given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs);health technology assessments and economic evaluations; clinical practice guidelines andcoverage policies of other health systems.ResultsAnkylosing Spondylitis:Two systematic reviews and four RCTs were included.One RCT compared Etanercept (n=379) with Sulfasalazine (n=187), and showed a 76%improvement for Etanercept vs. 53% for Sulfasalazine (p=0.0001) at Week 16 in the joint motionassessment and overall physical activity using ASAS 20 criteria. At one year follow-up, nostructural radiological changes were observed in the joints.One RCT including 279 patients showed that 61.2% of the Infliximab-treated patients respondedwith ASAS 20 criteria at 24 weeks vs. 19.2% in the placebo group (p<0.001). There was alsoimprovement in inflammation as shown in Magnetic Resonance Imaging with a 12-month followup.One RCT including 315 patients, showed that a 58.2% of the Adalimumab group vs. 20.6% in theplacebo group achieved ASAS 20 improvement criteria at Week 12 (p<0.001).One RCT including patients with reactive AS refractory to NSAIDs or DMDs assessed Golimumab(N= 138) vs. placebo (N=78) with a 3-month follow-up. It showed an ASAS 20 improvement of59.4% for Golimumab vs. 21.8% for placebo (p<0.001) at 14 weeks and an ASAS 20 improvementof 43.5% vs. 15.4% (p<0.001) at Week 24.The European Practice Guidelines recommend the use of anti-TNF-alpha in patients with activeankylosing spondylitis for more than 4 weeks, a BASDAI score ≥ 4 (0?10) and one therapy with atleast two NSAIDs for 4 weeks at the recommended dose. Patients with axial manifestations maystart anti-TNF-alpha therapy without having previously received DMDs. Patients with peripheralarthritis should have an insufficient response to at least one corticosteroid administration locally (ifappropriate) and should have received an adequate therapy with DMDs, preferably sulfasalazine.Patients with enthesitis (ligament inflammation) should have received an unsuccessful therapylocally before starting anti-TNF-alpha drugs.The EMA recommends the use of Golimumab for severe axial spondyloarthritis without radiologicalsigns of ankylosing spondylitis not responding to NSAIDs.Reactive Arthritis:No RCTs or studies of adequate methodological quality were found to enable efficacy assessmentfor this indication. The clinical practice guidelines do not describe specific recommendations.ConclusionsThe quality of the evidence found is high for ankylosing spondylitis and very low for reactivearthritis.Anti-TNF-alpha therapy has proved to better control ankylosing spondylitis inflammatory symptomswhen compared to placebo or DMDs. The clinical practice guidelines recommend their use inpatients refractory to standard therapy with active disease for over 4 weeks and a BASDAI score ≥4 (0?10). Patients with axial manifestations may start anti-TNF-alpha therapy without havingpreviously received DMDs. In patients with peripheral arthritis, they are indicated after failure tosulfasalazine therapy.No evidence was found demonstrating anti-TNF-alpha efficacy in reactive arthritis.No evidence or recommendations were found comparing the relative effectiveness of the differentanti-TNFs-alpha drugs.