Rajiv Gandhi Institute of Health Science, Karnataka, Bangalore

RAJIV GANDHI INSTITUTE OF HEALTH SCIENCE, KARNATAKA, BANGALORE

ANNEXURE – II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. NAME OF THE CANDIDATE AND DR. SAJITH PRASAD ADDRESS (in block letters) PG STUDENT, MD (GM) BANGALORE MEDICAL COLLEGE AND RESEARCH INSTITUTE BANGALORE

2. NAME OF THE INSTITUTION BANGALORE MEDICAL COLLEGE AND RESEARCH INSTITUTE BANGALORE

3. COURSE AND STUDY OF THE MD GENERAL MEDICINE SUBJECT

4. DATE OF ADMISSION TO THE 31-05-2008 COURSE

5. TITLE OF THE TOPIC ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES (ANTI-CCP) IN RHEUMATOID ARTHRITIS

6. BRIEF RESUME OF THE INTENDED WORK 6.1 NEED FOR THE STUDY

Besides the rheumatoid factor (RF), another group of autoantibodies has been recently been detected in serum of patients with RA patients: the anti-cyclic citrullinated peptide antibodies (anti-CCP) . The presence of rheumatoid factor is not specific for RA, as rheumatoid factor is found in 5% of healthy people. The frequency of rheumatoid factor in the general population increases with age, and 10-20% of individuals >65 years have a positive test1.The sensitivity of RF in rheumatoid arthritis is has been found to be about 60-80%2,4 Antibodies to CCP is the latest serological marker available for the diagnosis of RA. It is tested by ELISA and several studies have shown it to have more specificity (98%)3,4 and a similar sensitivity to RF in rheumatoid arthritis. Anti-citrullinated proteins are locally produced in inflamed joints2.Commercially done assays now are anti-CCP 2 assay5.

6.2 REVIEW OF LITERATURE

Study conducted by Kunihiro Nishimura et al.4,“Meta-analysis: Diagnostic Accuracy of Anti–Cyclic Citrullinated Peptide Antibody and Rheumatoid Factor for Rheumatoid Arthritis” concluded that anti-CCP antibodies are more specific than RF for diagnosing rheumatoid arthritis and may better predict erosive disease. The study showed a sensitivity of 67% and specificity of 95% for anti-CCP antibodies in rheumatoid arthritis.

Study conducted by Pooja Khosla et al.5,“Anti-CCP antibodies in Rheumatoid arthritis” concluded that Anti CCP-2 antibodies show a great promise as a diagnostic marker of RA as they can be detected very early in RA. They may predict the eventual development into RA when found in undifferentiated arthritis. They have also shown the ability to distinguish between erosive and non erosive disease, making them a good prognostic marker.

Study conducted by Marja-Kaisa Koivula et al.6,“Autoantibodies binding to citrullinated telopeptide of type II collagen and to cyclic citrullinated peptides predict synergistically the development of seropositive rheumatoid arthritis” concluded that autoantibodies to citrullinated telopeptides of type I and II collagen and to CCPs exert a synergistic effect on the risk of seropositive RA.

Study conducted by Ger J.M. Pruijn et al.7,“Anti-CCP Antibody Detection Facilitates Early Diagnosis and Prognosis of Rheumatoid Arthritis” concluded that Anti-CCP is (i) highly specific for the disease, (ii) able to distinguish RA from other arthritides that mimic RA, (iii) present in the majority of patients (good sensitivity), (iv) detectable very early in the disease, and (v) helpful in predicting disease outcome.

Study conducted by T.B Niewold et al.8,“Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis” concluded that anti-CCP antibodies are a highly specific marker for RA in several diverse patient groups. Anti-CCP antibodies also identify a subset of patients who are likely to have substantial ongoing disease activity, accrue more damage, and who will probably benefit most from early aggressive treatment .Anti-CCP antibodies tend to remain stable or decline slightly with treatment, and have not been found frequently in non-RA inflammatory or arthritic diseases.

Study conducted by A Kastbom et al.9,“Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project)” concluded that anti-CCP status at the time of diagnosis of early RA is a valuable predictor of disease course in early RA. 6.3 OBJECTIVES OF THE STUDY

1. To compare the diagnostic sensitivity of anti-CCP antibody with rheumatoid factor in Rheumatoid arthritis. 2. To correlate anti-CCP antibody positive status with erosive disease and extra- articular manifestations.

7. MATERIALS AND METHODS

7.1 SOURCE OF DATA

Study will be conducted on patients admitted to hospitals attached to BMCRI including Victoria and Lady Curzon and Bowring hospitals.

7.2 METHOD OF COLLECTION OF DATA

40 patients diagnosed with Rheumatoid arthritis will be taken up for the study. Intended study is a cross sectional study.

INCLUSION CRITERIA: All patients diagnosed to have Rheumatoid arthritis using revised ACR criteria.

EXCLUSION CRITERIA: Patients having other connective tissue disorders along with Rheumatoid arthritis e.g. SLE, Sjogren’s syndrome etc

DURATION OF STUDY: Over a period of two years from November 2008 to November 2010

STATISTICAL ANALYSIS: data will be analysed using chi-square test

7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS? IF SO PLEASE DESCRIBE BRIEFLY:

The following investigations will be done on the patients

1) Complete blood count with differential count 2) Chest X-ray 3) X-ray of hand joints and other joints involved 4) Rheumatoid factor 5) Anti-CCP antibody 6) ANA if needed 7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3? Yes

8. LIST OF REFERENCES 8.1 TEXT BOOK REFERENCES: 1) Peter A Lipsky. Rheumatoid Arthritis.Fauci, Braunwald, Kasper, Hauser, Longo, Jameson, Loscalzo, HARRISON’S PRINCIPLES OF INTERNAL MEDICINE Volume II ,17TH Edition ; McGraw Hill Publications 2008 ;314:2083-2092

8.2 JOURNAL REFERENCES 1) Tsuneyo Mimori.Clinical significance of Anti-CCP antibodies in Rheumatoid Arthritis. Journal of Internal Medicine.2005; 44:112-1126

2) Sumeet A, Ramnath M, Anitha A.Autoantibodies in Rheumatoid Arthritis : association with severity of disease in rheumatoid arthritis.Journal of Clinical Rheumatology .2007; 26: 201–204

3) Kunihiro N, Daisuki S,Yoshinora K, Goh T, Takashi N, Seiji K et.al. Meta- analysis:Diagnostic Accuracy of Anti–Cyclic Citrullinated Peptide Antibody and Rheumatoid Factor for Rheumatoid Arthritis.Annals of Internal Medicine. 2007; 146: 797-808

4) Pooja K, Shankar S, Lalit Duggal. Anti-CCP antibodies in Rheumatoid arthritis. Journal of Indian Rheumatology Association 2004;12:143 -46

5) Marja KK, Markku H, Jarmo R, Paul K, Harri R, Timo P, Juha R.Autoantibodies binding to citrullinated telopeptide of type II collagen and to cyclic citrullinated peptides predict synergistically the development of seropositive rheumatoid arthritis.Annals of Rheumatic Disease 2007;66:1450-1455.

7) Ger JMP,Erik R. Vossenaar, Jan W Drijfhout, Walther J.Van Venrooij and Albert J.W Zendman.Anti-CCP Antibody Detection Facilitates Early Diagnosis and Prognosis of Rheumatoid Arthritis. Current Rheumatology Reviews 2005;1:1- 7.

8) TB Niewald, MJ Harrison and S.A Paget.Anti-CCP antibody testing as a diagnostic and prognostic tool in Rheumatoid arthritis.QJ Med 2007; 100:193-201. 9) A Kastbom , G Strandberg, A Lindros, T Skogh “Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project)”.Ann Rheum Dis 2004;63:1085-1089.

9. SIGNATURE OF THE CANDIDATE:

Dr SAJITH PRASAD

10. REMARKS OF THE GUIDE: Anti-CCP antibody as a simple diagnostic tool in Rheumatoid arthritis is highly specific and sensitive and also correlates well with disease activity especially erosive arthritis and extra-articular manifestations when compared to rheumatoid factor which is routinely done. Hence a simple laboratory test in diagnosing Rheumatoid arthritis and assessing the activity as a routine procedure will assist in further management of the disease.

11. NAME AND DESIGNATION OF: ( in block letters)

11.1 GUIDE : PROF DR ANANDA KUMAR M, MD PROFESSOR OF MEDICINE, BANGALORE MEDICAL COLLEGE AND RESEARCH INSTITUTE, BANGALORE.

11.2 SIGNATURE:

11.3 CO-GUIDE (IF ANY) : 11.4 SIGNATURE

11.5 HEAD OF THE : PROF. DR. VASANTHA KAMATH, MD, FICP DEPARTMENT PROFESSOR AND HOD, DEPARTMENT OF MEDICINE, BANGALORE MEDICAL COLLEGE AND RESEARCH INSTITUE, BANGALORE.

11.6 SIGNATURE :

12 12.1 REMARKS OF THE CHAIRMAN AND PRINCIPAL:

12.2 SIGNATURE: