Get access

Abatacept for rheumatoid arthritis

  • Review
  • Intervention

Authors


Abstract

Background

Abatacept inhibits the co-stimulation of T cells and disrupts the inflammatory chain of events that leads to joint inflammation, pain, and damage in rheumatoid arthritis.

Objectives

To assess the efficacy and safety of abatacept in reducing disease activity, pain, and improving function in people with rheumatoid arthritis.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (from 1966), EMBASE (from 1980), ACP Journal Club (from 2000), and Biosis Previews (from 1990) in March 2007 and December 2008. We contacted authors of included studies and the abatacept manufacturer.

Selection criteria

Randomized controlled trials comparing abatacept alone, or in combination with disease-modifying anti-rheumatic drugs (DMARDs) or biologics, to placebo or other DMARDs or biologics in patients with moderate to severe rheumatoid arthritis.

Data collection and analysis

Two authors independently assessed search results and risk of bias, and extracted data. We obtained adverse event data from trials, long-term extension studies, and regulatory agencies.

Main results

Seven trials with 2908 patients were included. Compared with placebo, patients in the abatacept group were 2.2 times more likely to achieve an ACR 50 response at one year (RR 2.21, 95% confidence interval (CI) 1.73 to 2.82) with a 21% (95% CI 16% to 27%) absolute risk difference between groups. The number needed to treat to achieve an ACR 50 response was 5 (95% CI 4 to 7). Significant improvements in physical function and a reduction in disease activity and pain were found in abatacept-treated patients compared to placebo. One RCT found abatacept significantly slowed the radiographic progression of joint damage at 12 months compared to placebo, although it is not clear what the clinical relevance of this difference may be. There may be a risk of attrition bias. Total adverse events were greater in the abatacept group (RR 1.05, 95% CI 1.01 to 1.08). Other harm outcomes were not significant with the exception of a greater number of serious infections at 12 months in the abatacept group (Peto odds ratio 1.91 (95% CI 1.07 to 3.42). Serious adverse events were increased when abatacept was given in combination with other biologics (RR 2.30, 95% CI 1.15 to 4.62).

Authors' conclusions

There is moderate-level evidence that abatacept is efficacious and safe in the treatment of rheumatoid arthritis. Abatacept should not be used in combination with other biologics to treat rheumatoid arthritis. The withdrawal and toxicity profile appears acceptable at the present time but further long-term studies and post-marketing surveillance are required to assess harms and sustained efficacy.

Plain language summary

Abatacept for rheumatoid arthritis

This summary of a Cochrane review presents what we know from research about the effect of abatacept on rheumatoid arthritis. Although expensive, if supported by the overall body of evidence, the claims of their benefit upon both symptoms and radiographic progression, and their low rate of short term side effects make them of great interest to patients with RA.

The review shows that in people with rheumatoid arthritis:

- Abatacept probably reduces joint damage as seen on the x-ray.
- Abatacept probably improves pain, function and other symptoms of rheumatoid arthritis. 
- Abatacept probably reduces disease activity.

We do not have precise information about side effects and complications. This is particularly true for rare but serious side effects.  Possible side effects may include a serious infection or upper respiratory infection.  Rare complications may include certain types of cancer. 

What is rheumatoid arthritis and what is abatacept?
When you have rheumatoid arthritis, your immune system, which normally fights infection, attacks the lining of your joints. This makes your joints swollen, stiff and painful. The small joints of your hands and feet are usually affected first. There is no cure for rheumatoid arthritis at present, so the treatments aim to relieve pain and stiffness and improve your ability to move. 

Abatacept is one of a group of medications called selective costimulation modulators (immunomodulators). It works by blocking the activity of T-cells, a type of immune cell in the body that causes swelling and joint damage in people who have rheumatoid arthritis.

Best estimate of what happens to people with rheumatoid arthritis who take abatacept:

X-rays of the joints

-There was no damage to joints of people who took abatacept after 12 months.
-The damage to joints of people who took a placebo was 0.27 units on a scale of 0 to 145 units.

Pain (higher scores mean worse or more severe pain)

- People who took abatacept rated their pain to be 12 points lower on a scale of 0 to 100 after 12 months with abatacept (12% absolute improvement).

-People who took abatacept rated their pain to be 37 on a scale of 0 to 100 after 12 months.
-People who took a placebo rated their pain to be 49 on a scale of 0 to 100. 

ACR 50 (number of tender or swollen joints and other outcomes such as pain and disability)

-20 more people out of 100 experienced improvement in the symptoms of their rheumatoid arthritis after 12 months with abatacept (20% absolute improvement).

-37 people out of 100 experienced improvement in the symptoms of their rheumatoid arthritis.
-17 people out of 100 who took a placebo experienced improvement.
 

Physical Function

-25 more people out of 100 had better physical function after 12 months with abatacept (25% absolute improvement).
-64 people out of 100 had better physical function.
-39 people out of 100 who took a placebo had better physical function.

Disease activity

-32 more people out of 100 were considered to have low disease activity of their rheumatoid arthritis after 12 months with abatacept (32% absolute improvement).
-42 people out of 100 were considered to have low disease activity of their rheumatoid arthritis.
-10 people out of 100 who took a placebo were considered to have low disease activity of their rheumatoid arthritis.

 

Ringkasan bahasa mudah

Abatacept untuk radang sendi reumatoid

Ringkasan sorotan Cochrane ini menunjukkan apa yang kita ketahui daripada kajian tentang kesan abatacept terhadap artritis rheumatoid (RA).Walaupun mahal, jika disokong oleh bukti secara keseluruhan, tuntutan faedah ubat ini terhadap simptom dan perkembangan radiografi, dan kadar kesan sampingan jangka pendek yang rendah menjadikannya menarik kepada pesakit RA.

Ulasan ini menunjukkan orang yang mengalami artritis rheumatoid:

- Abatacept mungkin boleh mengurangkan kerosakan sendi seperti yang dilihat pada x-ray.
- Abatacept mungkin boleh mengurangkan sakit, meningkatkan fungsi, dan simptom artritis rheumatoid lain. 
- Abatacept mungkin mengurangkan aktiviti penyakit

Kami tidak mempunyai maklumat yang tepat tentang kesan sampingan dan komplikasi ubat ini. Ini adalah benar untuk kesan sampingan serius yang jarang berlaku. Kesan sampingan yang mungkin berlaku termasuk jangkitan yang serius atau jangkitan pernafasan atas.  Komplikasi yang jarang berlaku termasuklah beberapa jenis kanser. 

Apakah itu artritis rheumatoid dan apa itu abatacept?
Apabila anda mengalami artritis rheumatoid, sistem imun anda yang biasanya melawan jangkitan, menyerang lapisan sendi anda. Ini menyebabkan sendi bengkak, kejang, dan sakit. Sendi-sendi kecil di tangan dan kaki biasanya terjejas dahulu. Tiada ubat untuk artritis rheumatoid pada masa ini, oleh itu rawatan bertujuan melegakan sakit dan kekejangan dan meningkatkan keupayaan anda untuk bergerak. 

Abatacept adalah salah satu daripada kumpulan ubat yang dipanggil "selective costimulation modulators" (immunomodulators). Ia berfungsi menyekat aktiviti sel T, satu jenis sel imun dalam badan yang boleh menyebabkan sendi bengkak dan rosak pada orang yang mengalami artritis rheumatoid.

Anggaran terbaik terhadap apa yang berlaku kepada orang yang menghidap artritis rheumatoid dan mengambil abatacept:

X-ray untuk sendi

-Tidak ada kerosakan sendi bagi orang yang mengambil abatacept selepas 12 bulan.
-Kerosakan sendi untuk orang yang mengambil plasebo adalah 0.27 unit dalam skala yang bermula dari 0 sehingga 145 unit.

Kesakitan (skor yang lebih tinggi bermakna lebih teruk atau kesakitan yang lebih teruk)

-Orang yang mengambil abatacept selama 12 bulan mendapati bahawa kesakitan mereka telah dikurangkan sebanyak 12 markah dalam skala 0 hingga 100. (kesakitan mengurang sebanyak 12%)

-Orang yang mengambil ubat abatacept selama 12 bulan menilai kesakitan mereka sebagai 37 dalam skala 0 hingga 100.
-Orang yang mengambil plasebo menilai kesakitan mereka sebagai 49 dalam skala 0 hingga 100. 

ACR 50 (bilangan sendi yang sakit atau bengkak serta masalah lain seperti sakit dan hilang upaya)

-Lebih 20 orang daripada 100 orang mengalami pengurangan simptom artritis rheumatoid selepas pengambilan abatacept selama 12 bulan (pengurangan sebanyak 20%)

-37 daripada 100 orang mengalami pengurangan simptom radang sendi reumatoid selepas pengambilan abatacept.
-17 daripada 100 orang mengalami pengurangan simptom selepas pengambilan placebo.
 

Fungsi fizikal

-25 lebih ramai orang daripada 100 orang mempunyai fungsi fizikal yang lebih baik selepas penggunaan abatacept selama 12 bulan (pembaikan fungsi fizikal sebanyak 25%).
-64 daripada 100 orang mempunyai fungsi fizikal yang lebih baik selepas penggunaan abatacept.
-39 daripada 100 orang yang mengambil placebo mempunyai fungsi fizikal yang lebih baik.

Aktiviti penyakit

-32 lebih ramai orang daripada 100 dianggap mempunyai aktiviti penyakit yang rendah artritis rheumatoid selepas 12 bulan penggunaan abatacept (pembaikan sebanyak 32%).
-42 orang daripada 100 orang dianggap mempunyai aktiviti penyakit yang rendah untuk artritis rheumatoid selepas pengambilan abatacept.
-10 daripada 100 orang yang mengambil plasebo dianggap mempunyai aktiviti penyakit yang rendah untuk artritis rheumatoid.

Catatan terjemahan

Diterjemahkan oleh Raymond Chieng Siang Ching (Melaka Manipal Medical College). Disunting oleh Noorliza Mastura Ismail (Melaka Manipal Medical College) Untuk sebarang pertanyaan mengenai terjemahan ini sila hubungi raymondchieng@gmail.com

Laički sažetak

Abatacept za liječenje reumatoidnog artritisa

Ovaj sažetak Cochrane sutavnog pregleda predstavlja sažetak dokaza iz kliničkih istraživanja o djelotvornosti lijeka abatacepta za reumatoidni artritis (RA).  Iako je skup, ako se lijek abatacept pokaže kao djelotvoran i siguran, bio bi vrlo važan za oboljele od RA.

Ovaj pregled pokazuje da u osoba s reumatoidnim artritisom:

- Abatacept vjerojatno smanjuje oštećenje zglobova vidljivo na rendgenskoj snimci.
- Abatacept vjerojatno ublažava bol, poboljšava funkciju i ublažava ostale simptome reumatoidnog artritisa.
- Abatacept vjerojatno smanjuje aktivnost bolesti.

Nemamo precizne informacije o nuspojavama i komplikacijama. To osobito vrijedi za rijetke, ali ozbiljne nuspojave.  Mogući štetni učinci uključuju ozbiljnu infekciju ili infekciju gornjeg dišnog sustava.  Rijetke komplikacije mogu uključivati neke vrste karcinoma. 

Što je reumatoidni artritis i što je abatacept?

Kod reumatoidnog artritisa, imunološki sustav koji obično suzbija infekcije, napada ovojnice zglobova. Zbog toga su zglobovi otečeni, ukočeni i bolni. Obično su prvo pogođeni mali zglobovi u rukama i nogama. Trenutačno ne postoji lijek za reumatoidni artritis te je cilj terapije olakšanje boli i ukočenosti zglobova i poboljšanje pokretljivosti. 

Abatacept je lijek iz skupine lijekova koji se nazivaju selektivni modulatori ko-stimulacije (imunomodulatori). Djeluju tako što blokiraju aktivnost T-stanica, vrste imunoloških stanica u tijelu koje uzrokuju oticanje i oštećenje zglobova u osoba boluju od RA.

Najbolja procjena onoga što se događa osobama s reumatoidnim artritisom koje uzimaju abatacept:

Rendgenska slika zglobova

-Nije bilo oštećenja zglobova u osoba koje su uzimale abatacept nakon 12 mjeseci.
-Oštećenje zglobova u osoba koje su uzimale placebo bilo je 0,27 jedinica na ljestvici od 0 do 145 jedinica.

Bol (više vrijednosti znače goru ili ozbiljniju bol)

-Osobe koje su uzele abatacept procijenile su svoju bol kao 12 bodova nižu na ljestvici od 0 do 100 nakon 12 mjeseci uzimanja abatacepta (12% apsolutnog poboljšanja).

-Osobe koje su uzimale abatacept ocijenile su svoju bol ocjenom 37 na ljestvici od 0 do 100 nakon 12 mjeseci uzimanja abatacepta.
-Osobe koje su uzele placebo ocijenile su svoju bol kao 49 na ljestvici od 0 do 100. 

ACR 50 (broj osjetljivih ili otečenih zglobova i drugi ishodi, poput boli i onesposobljenosti)

-20 ljudi više od 100 doživjelo je poboljšanje simptoma RA nakon 20 mjeseci terapije abataceptom (20% apsolutno poboljšanje).

-37 ljudi od 100 doživjelo je poboljšanje simptoma njihova RA.
-17 osoba od 100 koje su uzele placebo doživjele su poboljšanje.
 

Tjelesna funkcija

-25 ljudi više od 100 imalo je bolju tjelesnu funkciju nakon 12 mjeseci uzimanja abatacepta (25% apsolutno poboljšanje).
-64 osobe od 100 imale su bolju tjelesnu funkciju.
-39 osoba od 100 koje su uzele placebo imale su bolju tjelesnu funkciju.

Aktivnost bolesti

-32 osobe više od 100 imale su manju aktivnost bolesti njihova RA nakon 12 mjeseci terapije abataceptom (32% apsolutnog poboljšanja).
-42 osobe od 100 imale su manju aktivnost bolesti njihova RA.
-10 osoba od 100 koje su uzele placebo imale su manju aktivnost bolesti njihova RA.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Livia Puljak
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

Ancillary