WRITE A NOTE ON ASSESSMENT OF PATIENT WITH ANKYLOSING SPONDYLITIS FOR BIOLOGIC THERAPY ?
A 1 INTRODUCTION
1 TNFα inhibitor therapy is currently the only effective therapy for patients with disease that has failed to respond to conventional therapy
2 TNFα inhibitor treatment is more effective at preventing articular damage in peripheral joints than in axial ones.
3 It is important to treat patients at an early stage of disease to reduce disease progression moreover it is necessary to identify causes of therapy inefficacy in preventing joint damage in axial subsets
4 TNF blockers target a cell protein that causes inflammation in the body. IL-17 plays a role in your body’s defense against infection and also has a role in inflammation.
A ) TNF blockers help reduce pain, stiffness, and tender or swollen joints.
B ) They are administered by injecting the medication under the skin or through an intravenous line.
C ) The five TNF blockers approved by the Food & Drug Administration to treat ankylosing spondylitis are -
1 Adalimumab (Humira)
2 Certolizumab pegol (Cimzia)
3 Etanercept (Enbrel)
4 Golimumab (Simponi; Simponi Aria)
5 Infliximab (Remicade)
6 Secukinumab (Cosentyx) is the first IL-17 inhibitor approved by the FDA for the treatment of ankylosing spondylitis.
5 TNF blockers and IL-17 inhibitors can reactivate latent tuberculosis and make you more prone to infection
6 The most common side effects of biologics include nausea, abdominal pain, headaches, injection-site-related reactions (pain, itching, swelling), upper respiratory infections (e.g., bronchitis, cold, sore throat), or infusion-related reactions (rash, flushing, or headache).
7 Serious side effects include severe allergic reactions, serious infections including tuberculosis and sepsis (a bacterial infection that spreads throughout the body), blood problems (e.g., decreased number of blood cells), malignancies, and nervous system disease (with symptoms including numbness, tingling, and vision problems
PROBLEMS ENCOUNTERED ON ADMINISTRATION OF BIOLOGICS
1 REACTIVATION OF LATENT TUBERCULOSIS , HEPATITIS B AND C , HERPES ZOSTER
2 RISK OF LYMPHOMA AND SOLID TUMORS
3 DEMYELINATING DISORDER OF CNS
4 HYPERLIPIDEMIA
5 NOT TO BE INDICATED FOR CONGESTIVE HEART FAILURE
6 ELEVATED HEPATIC TRANSAMINASE LEVELS
7 DRUG ERUPTIONS - leucocytoclastic vasculitis, lichenoid drug reaction, perniosis‐like eruption, superficial granuloma annulare and acute folliculitis
ASSESSMENT PROTOCOL
OR
PRECAUTIONS AND SCREENING BEFORE SELECTING AND STARTING BIOLOGICAL THERAPY
A) Screening and Prophylaxis for Latent Tuberculosis
1 In view of the risk of TB reactivation under biological therapy, it is advisable to assess a patient’s TB history and exposure.
2 Screening for latent TB is recommended for all biological agents, except rituximab, where clinical vigilance would suffice in view of the paucity of arguments pointing towards an elevated tuberculosis risk with this drug
3 Latent tuberculosis is sometimes operationally defined as the combination of absence of TB signs or symptoms in the presence of one or more risk factors for TB (TB exposure or underlying disease), together with a positive PPD (purified protein derivative) skin test
4 However, direct diagnosis of latent tuberculosis infection is not possible.
SO , The diagnostic tests used to identify individuals latently infected with M. tuberculosis -
A ) the in vivo tuberculin skin test
1 - The tuberculin skin test is the classic in vivo TB screening test in which tuberculin PPD is injected intradermally.
2 - In the presence of a TB immune response, PPD injection is followed by appearance of an induration at the injection site.
3 - The diameter of the induration considered positive depends upon the underlying risk status of the patient.
4 - In TB screening of RA patients before the start of biological therapy indurations above 5 mm are usually considered positive VV IMP
5 - In the follow-up of patients under biological therapy an increase in induration diameter by 6mm or more would be indicative of TB reactivatiON
6 - Tuberculin skin testing is not very reliable in immunocompromised populations. The PPD response was shown to be subdued in RA patients and influenced by previous BCG vaccination
B ) The tuberculosis-specific interferon-gamma release assay (IGRA) as an alternative screening for latent TB has been adopted so eagerly by the clinical community, as to interfere with the proper investigation of its predictive value
Although a number of studies report better results in RA patients with IGRA in comparison with tuberculin skin testing and good agreement between results of different IGRAs
IGRA testing suffers from a certain percentage of indeterminate results, necessitating the combination of both screening tests
C ) Patients with a positive TB screening test should be assessed for active disease with a chest X-ray and treated with appropriate prophylactic TB therapy.
1 - Chemoprophylaxis for latent TB usually consists of isoniazid single therapy for 9 months, or alternatively, rifampicin for 4 months
2 - In regions with TB drug resistance of >10% combination drug therapy must be considered.
TESTS TO BE ORDERED
1 Liver function tests should be monitored every two to four weeks during TB treatment, especially in patients concurrently taking potentially hepatotoxic medications
2 Hepatitis B and C Screening and Antiviral Prophylaxis
A ) Prior to initiation of biological therapy hepatitis B serology should be assessed by HBsAg, anti-HBs and anti-HBc tests.
B ) Negative patients should be considered for hepatitis B vaccination.
C ) Patients positive for hepatitis B core antibodies have gone through active hepatitis infection and should be monitored closely for reactivation.
D ) Addition of antiviral prophylaxis should be considered on an individual patient basis.
3 - Screening for hepatitis C virus prior to biological therapy is appropriate In view of the role of TNF in hepatitis C infection and the relative safety of TNF blockers in patients with hepatitis C infection, no change of antiviral therapy is needed, provided there is adequate monitoring of liver enzymes and viral load
4 - HIV screening prior to biological therapy is recommended in patients with risk behavior. Biological therapy should be reserved for stable HIV positive patients with adequate (>200/ml) CD4 cell counts
5 - Vaccination
RA patients treated with biological therapy must be regarded as immunocompromised individuals and are as such at increased risk of infection and complications for some vaccine-preventable diseases. The benefits of vaccination in this population are even greater than in the general population, but vaccination coverage is surprisingly low
VV IMP -
1 Like in all immunocompromised individuals, live vaccines (measles-mumps-rubella, varicella and zoster vaccine, yellow fever, oral poliomyelitis) are contraindicated in RA patients under biological therapy.
2 For inactivated vaccines, biological therapy may have a negative impact on the quality of the vaccine-induced immune response.
3 Therefore, vaccination status should be checked and updated as appropriate before the start of biological therapy.
4 Live vaccines need to be given 3 to 4 weeks prior to the start of therapy to ensure clearance of the vaccine virus before the immune response is impaired.
5 The waiting period needed before administering live vaccines after biological therapy discontinuation depends on the type, dose and duration of the therapy
6 As a rule of thumb, a period of 3 months is estimated to be sufficient for restoration of the immune response.
7 For rituximab, B cell repletion and adequate restoration of the immune response may require a longer period of 6 to 10 months
8 Inactivated vaccines can be safely administered during biological therapy.
9 Although the influenza, pneumococcal and hepatitis B vaccines have been demonstrated to be safe and effective in RA patients treated with biologicals, a number of studies indicate that the quality of the vaccine-elicited immune response in these patients is lower, with either reduced seroconversion rates after vaccination – leaving a subset of patients unprotected - or reduced quantity or quality of the antibody response to the vaccine, which in turn may have a negative effect on the duration of protection
TESTS TO BE ORDERED VV IMP
1 CBC
2 ESR
3 CRP
4 PPD
5 RA FACTOR
6 CCP
7 PREGNANCY TEST
8 HIV
9 ACR N , ACR 20
10 HAQ
11DAS 28 , 44 CRP
12 AST
13 ALT
14 CREATININE
15 ALBUMIN
16 X RAY