Japan College of Rheumatology 2009 guidelines for the use of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, in rheumatoid arthritis

Abstract

The introduction of biological agents targeting tumor necrosis factor-alpha (TNF-α) has brought about a paradigm shift in the treatment of rheumatoid arthritis (RA). Although these anti-TNF agents have excellent efficacy against RA, a substantial number of patients still show inadequate responses. In Western countries, such patients are already being treated with new classes of antirheumatic drugs such as abatacept and rituximab. Tocilizumab (TCZ) is a humanized monoclonal antibody developed in Japan against the human interleukin-6 (IL-6) receptor. TCZ does not only alleviate the signs and symptoms of RA but also seems to prevent progressive bone and joint destruction. However, there is a concern that TCZ might increase the risk of adverse events such as infections since IL-6 plays a pivotal role in the immune system. Calculating the relative risks of specific adverse outcomes with TCZ use remains difficult, due to insufficient patient numbers enrolled in clinical trials to date. This review presents tentative guidelines for the use of TCZ for RA patients prepared by the Japan College of Rheumatology and based on results of clinical trials in Japan and Western countries. The guidelines are intended as a guide for postmarketing surveillance and clinical practice, and will be revised periodically based on the surveillance.

Canadian Rheumatology Association Recommendations for the Pharmacological Management of Rheumatoid Arthritis with Traditional and Biologic Disease-modifying Antirheumatic Drugs: Part II Safety

“…All guidelines with recommendations for anti-TNF therapy recommended screening for LTBI prior to initiation of anti-TNF therapy 16,22,23,25,26,30,33,53,54,55,56,57,58,59 . Seven guidelines commented on screening prior to ABAT 22,28,30,31,32,55,57 and 7 prior to TCZ 22,24,27,30,32,55,57 , and all recommended LTBI screening, although 5 guidelines highlighted that the magnitude of risk is unknown 22,24,27,30,55 . Eight guidelines commented on screening prior to RTX 22,29,30,31,32,55,57,60 .…”

“…. Three guidelines recommended that IGRA could be considered as an alternative to TBST 22,24,27 , and 3 suggested that they may have a role, but their role is currently unclear 30,31,55 . Three guidelines suggested that they might have a role in patients who have received prior BCG vaccine 30,31,55 , with one guideline adding that they may also have a role in patients receiving immunosuppressants or in patients who have had prior non-TB mycobacterial infection 22 .…”

“…The search identified 12 clinical practice guidelines and 1 consensus statement that addressed perioperative management in RA patients treated with biologic DMARD (AGREE rating: Recommend (R) = 2, Recommend with provisos (R*) = 11). All guidelines recommended holding biologic DMARD prior to surgery 22,23,24,25,26,27,28,29,30,31,32 except 2009 BSR guidelines 14 , which suggest that biologic DMARD could be continued in most cases of elective orthopedic surgery. Timing for withholding therapy before surgery.…”

“…Eight guidelines recommended that biologics may be restarted postoperatively if there is no evidence of infection and wound healing is satisfactory 22,23,25,26,27,28,30,31,33 . A Spanish guideline 32 suggested waiting 10-14 days and a Japanese TCZ guideline 24 31 and Spanish 2010 32 guidelines referred to the same 3 cohort studies that examined risks for postoperative infections in RA patients treated with anti-TNF. The largest was a retrospective cohort study of 768 RA patients that underwent 1219 elective orthopedic procedures and reported a nonsignificant increased odds of surgical site infections in patients who continued anti-TNF therapy (OR 1.5, 95% CI 0.43-5.2) 34 .…”

Biological Therapy and Infection in Rheumatoid Arthritis Patients: Modern Aspects

“…Также сходной c иФНО-α была структура инфекционных осложнений, которые включали Пн, флегмону, Herpes zoster-инфекцию, бактериальный артрит, реактивацию латентных инфекций, в т. ч. микобактериальных и т. д. В отдельных случаях СКИ приводили к летальному исходу. Эксперты Японской коллегии ревматологов полагают, что для минимизации развития оппортунистических инфек-ций у больных РА перед назначением ТЦЗ необходимо соблюдение следующих условий; а) число лейкоцитов периферической крови ≥ 4000/мм 3 , б) число лимфоцитов периферической крови ≥1000/мм 3 , в) отрицательный сывороточный тест на 1,3-бета-D-глюкан (маркер глубо-ких инвазивных микозов) [38].…”