Treatmentofrheumatoidarthritis:Areviewofrecommendationsand emergingtherapy

Treatmentofrheumatoidarthritis:AreviewofrecommendationsandemergingtherapyJenniferN.Clements,PharmD,BCPS,CDE1 Desember 2011FormularyJournal ClinicalPharmacologyAbstract

Rheumatoid arthritis (RA) is characterized as a chronic, inflammatory disease in which the immune system destroys synovial joints and accessory structures.

Due to the progressive nature, this autoimmune condition can cause extra-articular complications within several organ systems.3

RA affects approximately 1% of adults all over the world.1,2Individuals are usually diagnosed between the third and fifth decade of life and women are 2 to 3 times more likely to be diagnosed than men.1,2

The etiology of RA is not fully understood, but environmental and genetic factors have been proposed as potential theories. Genetic predisposition results in the destructive nature of this autoimmune disease.2

For example, an individual with expression of a human leukocyte antigen (HLA) DR-4 antigen will be 3.5 times more likely to develop RA compared to someone with other HLA-DR antigens.2Other potential risk factors include female gender, use of oral contraceptives, tobacco use, and infectious agents.2

PATHOPHYSIOLOGY

In RA, the immune response will be activated in an early stage of life. This immune response could be triggered by genetic and environmental factors. Once the immune system is unbalanced, subclinical inflammation will occur due to activation of T cells from an antigen-presenting cell. Once T cells are proliferated, a cascade of events occurs in the immune system: activation of B cells and macrophages, as well as other proinflammatory mediators such as tumor necrosis factor (TNF) and interleukin (IL). As the immune system remains unchecked, symptoms associated with RA will occur and the criteria for the disease will be fulfilled. Once the diagnosis is confirmed, the pathologic inflammatory response can continue, resulting in joint destruction and extra-articular complications. Within a synovial joint, bone and cartilage erosion will occur, causing a swollen joint capsule and inflamed joint synovium. The extra-articular complications can occur over time and include infections, lymphomas, cardiovascular disease, and osteoporosis.1-3Dalam RA, respon imun akan diaktifkan dalam tahap awal kehidupan. Reaksi kekebalan bisa dipicu oleh faktor genetik dan lingkungan. Setelah sistem kekebalan tubuh tidak seimbang, peradangan akan terjadi karena aktivasi sel T dari sel antigen presenting. Setelah sel T menjamur, kaskade terjadi disistem kekebalan tubuh: aktivasi sel B dan makrofag, serta mediator pro inflamasi lainnya seperti tumor necrosis factor (TNF) dan interleukin (IL). Sistem kekebalan tubuh tetap terkendali, gejala yang berhubungan dengan RA akan terjadi dan kriteria untuk penyakit akan terpenuhi menjadi RA. Setelah diagnosis dikonfirmasi, respon inflamasi patologis dapat dilanjutkan, yang mengakibatkan kerusakan sendi dan komplikasi extraarticular. Dalam sinovial sendi, tulang dan tulang rawan erosi akan terjadi, menyebabkan kapsul sendi bengkak dan meradang sinovium sendi. Komplikasi extraarticular dapat terjadi dari waktu ke waktu dan termasuk infeksi, limfoma, penyakit kardiovaskular, dan osteoporosis.137CLINICAL PRESENTATIONRA can occur at any age, but in men onset before age 45 years is uncommon.1The disease can develop rapidly within weeks to months.3Commonly affected areas include the hands, wrists, elbows, knee, metatarsophalangeal joint, shoulder, and cervical spine. The area of joint involvement is symmetric and results in pain, morning stiffness lasting more than 1 hour, gelling (or locking with inactivity), tenderness, warmth, redness, and inflammation. Due to the autoimmune nature of the disease, constitutional symptoms will occur such as low-grade fever and malaise. As RA progresses, there can be extra-articular involvement leading to complications, such as vasculitis and pulmonary and cardiac issues.3PRESENTASI KLINISRA dapat terjadi pada semua usia, tetapi pada pria onset sebelum usia 45 tahun adalah uncommon.1 Penyakit ini dapat berkembang cepat dalam beberapa minggu ke bulan.3 Umumnya predileksinya termasuk tangan, pergelangan tangan, siku, lutut, sendi metatarsophalangeal, bahu, dan tulang belakang leher. Gejalanya simetris dan nyeri, kekakuan pagi berlangsung lebih dari 1 jam, nyeri tekan, panas, kemerahan, dan peradangan. Karena sifat penyakit autoimun, gejala konstitusional akan terjadi seperti demam low grade dan malaise.Apabila lama kelamaan, bisa ada keterlibatan extraarticular menyebabkan komplikasi, seperti vaskulitis dan paru dan masalah jantung. 3

8DIAGNOSA

klasifikasi baru Kriteria dapat diimplementasikan, 2 persyaratan harus dipenuhi untuk memastikan diagnosis RA: bukti sinovitis klinis setidaknya 1 sendi (termasuk sendi umum terlihat pada OA), dan mengesampingkan eritematosus sistemik lupus, asam urat, dan psoriasis arthritis.5 Ini akan memakan waktu, namun, untuk kriteria baru yang akan digunakan oleh para praktisi dan diimplementasikan dalam uji klinis.11TREATMENT OF RA

First, methotrexate or leflunomide is recommended for most patients with RA. Both agents have documented improvement in objective assessment of the disease and reduction in radiographic progression.

Combination therapy of a TNF antagonist and methotrexate can be used for patients with newly diagnosed or early RA.

If a patient fails a particular TNF antagonist with or without methotrexate, another DMARD with biologic activity can be initiated as long as the patient does not have any contraindications. Failure includes continuation or no improvement in symptoms within 3 to 6 months of pharmacologic therapy or development of poor prognosis.

Beberapa rekomendasi termasuk dalam pedoman pengobatan yang sudah diperbarui. Pertama, methotrexate atau leflunomide direkomendasikan untuk kebanyakan pasien dengan RA. Keduanya telah memberikan perbaikan dalam penilaian obyektif dari penyakit dan penurunan perkembangan radiografi. Tabel 2 merangkum rekomendasi untuk DMARDs tanpa aktivitas biologis dari terapi ACR.7 Kombinasi antagonis TNF dan metotreksat dapat digunakan untuk pasien yang baru didiagnosis atau awal RA. Jika pasien gagal suatu TNF antagonis tertentu dengan atau tanpa metotreksat, DMARD lain dengan aktivitas biologis dapat dimulai selama pasien tidak memiliki kontraindikasi. Kegagalan termasuk kelanjutan atau tidak ada perbaikan dalam gejala dalam waktu 3 sampai 6 bulan terapi farmakologis atau pengembangan prognosis buruk. 13Prior to initiation of any DMARD with biologic activity, all patients should be evaluated for active infections (including bacterial), herpes zoster infection, hepatitis B and C, and active or latent tuberculosis.

contraindication of TNF antagonists among patients with heart failure, lymphoma, or multiple sclerosis due to ongoing evidence of a causal relationship

NSAIDs have been used in the management of RA for several decades. NSAIDs inhibit COX to prevent further formation of prostaglandins and other related inflammatory mediators.

Sebelum memutuskan memulai setiap DMARD dengan aktivitas biologis, semua pasien harus dievaluasi untuk infeksi aktif ( termasuk bakteri), herpes zoster infeksi, hepatitis B dan C, dan TBC aktif atau laten.kontraindikasi dari TNF antagonis antara pasien dengan gagal jantung, limfoma, atau multiple sclerosis karena bukti berkelanjutan hubungan kausal. . NSAID telah digunakan dalam pengelolaan RA selama beberapa dekade. NSAID menghambat COX untuk mencegah lebih lanjut pembentukan prostaglandin dan mediator inflamasi terkait lainnya. Berdasarkan mekanisme kerjanya, NSAID berguna terapi adjuvant untuk manajemen gejala RA, sebagai kelas ini obat dapat mengurangi pembengkakan sendi, nyeri, dan pain.6,11,12 Semua NSAID menimbulkan sifat anti inflamasi dan, ketika diresepkan pada dosis tinggi, sama-sama efektif. Kelemahan utama dari NSAIDs termasuk profil keamanan (yaitu, gastrointestinal [GI], nefrotoksisitas, dan kardiovaskular). 14

CONCLUSIONFor the management of RA, the goal is to slow disease progression and prevent disability, such as loss of physical function. If approved, the emerging therapies for RA may not change the algorithm for RA and approval by FDA may be several years from the present time. Treatment guidelines, however, have been updated to support the use of early, aggressive treatment for a patient with RA. On the downside, economic considerations may be a drawback to existing, advanced therapies and emerging therapies. Additional evidence will be needed given that clinical trials with RA have exhibited wide variability in the patient population, clinical outcomes, and interventions. Long-term benefits remain to be seen, and more comparative studies with standard of care are needed.