|Year : 2016 | Volume
| Issue : 3 | Page : 126-128
Checklist prior to biologics: Indian perspective
Rajkiran Dudam1, Narsimulu Gumdal2
1 Department of Rheumatology, Star Hospitals, Hyderabad, Telangana, India
2 Department of Rheumatology, Yashoda Hospitals, Hyderabad, Telangana, India
|Date of Web Publication||11-Aug-2016|
Flat No 110, Oosman's SMR Vinay Elegance Apartments, Mettuguda, Kesav Nagar Colony, Secunderabad - 500 017, Telangana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Dudam R, Gumdal N. Checklist prior to biologics: Indian perspective. Indian J Rheumatol 2016;11:126-8
| Introduction|| |
The introduction of targeted biologic therapies for rheumatoid arthritis (RA) is one of the most significant advances in rheumatology. Targeting tumor necrosis factor (TNF) alpha (infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol) has been the epitome of bench-to-bedside research in rheumatology. This has opened up the way for other therapies such as blockade of other cytokines such as interleukin-1 (IL-1) (anakinra, canakinumab, and rilonacept) and IL-6 (tocilizumab, sirukumab, sarilumab, and olokizumab), co-stimulatory blockade (abatacept), and B cell depletion (rituximab). These have found utility in other rheumatic diseases also such as spondyloarthropathies, lupus, juvenile idiopathic arthritis, and inflammatory myositis. The current issue of the journal describes the experience with biologic agents in patients with RA from a center in Western India.  Currently, we are in an era of follow-on biologics (biosimilars or biocopies) which are competing with innovators or reference products.  Patient selection is the key for the usage of biologic disease-modifying antirheumatic drugs (DMARDs). Right patient selection for biologic should be based on following factors; ,
- Disease should be active as per disease activity assessment parameters of that particular disease
- Patients should be refractory to therapy with conventional agents
- Adherence to the therapy. For subcutaneous preparations, the patient's ability to self-administer or availability of assistants to administer the drug needs to be assessed.
Although many biologic agents are available in India, rheumatologists often feel that long-term biologic therapy is not tenable in many patients in the current situation predominantly due to financial constraints. A majority of these patients are self-financed and the remaining patients are able to get support from the government or insurance funding for a limited period. Very few are therefore able to continue long-term biologic therapy. To mitigate this, short-term intermittent biologic therapy is adapted by some rheumatologists. The reasoning behind this approach is that it would help in many patients achieving low disease activity status and further maintenance would be usually possible with a combination of synthetic DMARDs. There are no published controlled trials or prospective studies for this strategy, and a few rheumatologists are of the opinion that this would generate immunogenicity to these biologics.
To minimize the errors while prescribing biologics, it is essential to have a checklist and many countries follow the same. We propose a checklist which would serve as a quick reference before prescription of biologics [Table 1] and [Table 2]. 
| Dialogue with Patient|| |
Before commencing a biologic therapy, counseling and detailed discussion with the patient have to be done regarding disease activity and duration of therapy and therapeutic goals which are aimed and complications which are likely to develop [Table 2].
| History and Clinical Examination|| |
A history suggesting current or recent infections needs to be obtained and clinical examination to be done to rule out active infections, and if necessary, consultation with infectious disease specialists can be undertaken.
| Laboratory Evaluation|| |
Routine laboratory investigations including hemogram and renal and liver function tests should be done as screening before biologic therapy. Serum lipid profile needs to be done in patients before tocilizumab therapy. Significant deviations from normal range should be addressed appropriately.
| Tuberculosis|| |
Evidence shows that there is a significant risk of tuberculosis (TB) reactivation or new onset TB can occur with some biologics, especially anti-TNF agents. Hence, it becomes prudent for the treating rheumatologist to do a vigilant initial screening for TB and also on follow-up. Any symptom which hints toward TB should be thoroughly evaluated and treated accordingly. All patients should be assessed for risk of TB by taking a full patient history and reviewing the chest X-ray and physical examination.
- Current respiratory symptoms
- History of TB
- Family history and risk of exposure to TB.
A through physical examination is mandatory.
Chest X-ray needs to be done within the past 6 months and should be reviewed by the treating rheumatologist. If respiratory symptoms are present, a recent chest X-ray needs to be obtained, and if necessary, a consultation with the respiratory physician is warranted.
It should be done in patients receiving biologic response modifiers with increased risk of TB, especially when anti-TNF inhibitor agents are planned as therapy. In the Indian scenario, it is probably best done for all patients. This test is not required in patients who are on chemoprophylaxis and patients who have evidence of current TB or radiological evidence of scarring in the lungs due to TB. A strong positive test might indicate latent TB and decision to treat with anti-TB regimen should be taken in accordance with local hospital authorities. Most experts feel such patients to be treated with a combination regimen of isoniazid and rifampicin for at least 1 month before starting anti-TNF agents and can be continued for at least 4 months. Booster effects of repeat tests and false negative tests in patients receiving immunosuppressive therapy should be considered while interpreting the test.
QuantiFERON gold TB test is advocated in most of the clinical trials where biologics are studied, and patients with positive tests are excluded from the study. However, in real life, the thorough clinical examination is warranted in such patients and chemoprophylaxis may be indicated if anti-TNF therapy is planned.
| Vaccination|| |
It is prudent to vaccinate all patients who are subjected to biologic therapy unless contraindicated. Inactivated vaccines such as pneumococcal and influenza vaccines should be given to patients even though they may not offer absolute protection since their administration can reduce the risk of infection substantially.  They should be given before initiating biologic response modifiers, i.e., at least 4 weeks before, but this should not delay initiating therapy. Inactivated vaccines can be given during biologic therapy; however, the response might be inadequate.
Live vaccines should not be given during biologic therapy. If vaccination is indicated, it has to be given 4 weeks before starting biologic therapy. If live vaccines are required while the patient is on therapy, then the biologic has to discontinue for at least three half-lives of that particular biologic.
| Cardiac Function|| |
The complete clinical examination should be done and cardiovascular status should be assessed and looked for any evidence of heart failure. Patients with poor cardiac function should be referred to the cardiologist. Clinical trials would not include biologic therapy for patients with the New York Heart Association Class III or IV cardiac dysfunction; hence, controlled trials are not available. Observational studies report less risk or worsening. The physician has to decide depending on disease activity and risks and benefits of therapy.
| Demyelinating Disease|| |
Anti-TNF alpha agents could trigger demyelination, which further might evolve even after stopping the drug. Hence, one should consider avoiding anti-TNF in patients with risks of developing demyelinating diseases and discontinue if patients develop demyelinating diseases on therapy.
| Infusions|| |
Subcutaneous injections can be self-administered by patients or caregivers (nursing and physician assistants) but ensured that they are trained adequately in techniques of administering these drugs. There should be clear protocols for intravenous administration (including which solution to dilute in, the duration, and rate of infusion) and relevant personnel should be trained in this aspect. Availability of resuscitation kits along with trained staff handle anaphylaxis should be ensured.
To summarize, before initiating any biologic therapy, make sure that patients hemodynamics are stable, blood results are satisfactory, case is free from infections and not pregnant and not taking adequate contraception, and there are no malignancies and demyelinating diseases. The use of biologics needs to be rationalized and tailored on a case-to-case basis in the Indian scenario.
| References|| |
Singhal A, Bhakuni D, Marwaha V, Hande V, Bagga G. Experience of biological agents usage in patients with rheumatoid arthritis from a Western Indian center. Indian J Rheumatol 2016;11:22-6.
Dörner T, Kay J. Biosimilars in rheumatology: Current perspectives and lessons learnt. Nat Rev Rheumatol 2015;11:713-24.
Smolen JS, Landewé R, Breedveld FC, Buch M, Burmester G, Dougados M, et al.
EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014;73:492-509.
Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al.
American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) 2012;64:797-808.
Santhanam S, Swaminathan S. Vaccination in adults with autoimmune inflammatory rheumatic diseases. Indian J Rheumatol 2016;11:68-72.
[Table 1], [Table 2]