The paper presents the results of studies of acute phase reactants in the 60 treated patients with rheumatoid arthritis. Patients were divided into two groups, depending on the applied treatment: group I (n=30) was treated with methotrexate, sulfasalazine and hydroxychloroquine, and group II (n=30) with methotrexate. The results of our study shows that there is a statistically significant reduction in the value of acute phase reactants and clinical parameters after treatment in both investigated groups of patients, and also a significant statistical difference between the first and second group of treated patients.U radu su prikazani rezultati ispitivanja reaktanata akutne faze u 60 liječenih bolesnika s reumatoidnim artritisom. Bolesnici su bili podijeljeni u dvije skupine, ovisno o primijenjenoj terapiji: I. skupina (n=30) je liječena metotreksatom, sulfasalazinom i hidroksiklorokinom, a II. skupina (n=30) metotreksatom. Rezultati našega istraživanja pokazuju da postoji statistički značajno smanjenje vrijednosti reaktanata akutne faze i kliničkih parametara nakon liječenja u obje ispitivane skupine bolesnika, a također i značajna statistička razlika između prve i druge skupine liječenih bolesnika

Blerta Rexhepi

Ejup Pllana

Gani Dragusha

Masar Gashi

Mjellma Rexhepi

Sylejman Rexhepi

Vjollca Sahatçiu-Meka

English

Hrčak - Portal of scientific journals of Croatia

56(2)  Reumatizam 2009. 77Faculty of Medicine  University of PristinaRr. “Bulevardi i dëshmorëve” p.n.  10000 Pristina  KosovoZNANSTVENO PRIOPĆENJE SCIENTIFIC REPORTTHE EFFECTS OF COMBINED THERAPY OF RHEUMATOID ARTHRITIS ON THE ACUTE PHASE REACTANTSUČINCI KOMBINIRANE TERAPIJE REUMATOIDNOG ARTRITISA NA REAKTANTE AKUTNE FAZESylejman Rexhepi  Mjellma Rexhepi  Vjollca Sahatçiu-MekaEjup Pllana  Gani Dragusha  Masar Gashi  Blerta RexhepiSummaryThe paper presents the results of studies of acute phase reactants in the 60 treated patients with rheuma-toid arthritis. Patients were divided into two groups, depending on the applied treatment: group I (n=30) was treated with methotrexate, sulfasalazine and hy-droxychloroquine, and group II (n=30) with metho-trexate. The results of our study shows that there is a statistically signifi cant reduction in the value of acute phase reactants and clinical parameters after treatment in both investigated groups of patients, and also a sig-nifi cant statistical difference between the fi rst and sec-ond group of treated patients.Keywordsrheumatoid arthritis, combined therapy, acute phase reactantsSažetakU radu su prikazani rezultati ispitivanja reakta-nata akutne faze u 60 liječenih bolesnika s reumato-idnim artritisom. Bolesnici su bili podijeljeni u dvi-je skupine, ovisno o primijenjenoj terapiji: I. skupi-na (n=30) je liječena metotreksatom, sulfasalazinom i hidroksiklorokinom, a II. skupina (n=30) metotreksa-tom. Rezultati našega istraživanja pokazuju da posto-ji statistički značajno smanjenje vrijednosti reaktana-ta akutne faze i kliničkih parametara nakon liječenja u obje ispitivane skupine bolesnika, a također i značaj-na statistička razlika između prve i druge skupine li-ječenih bolesnika.Ključne riječireumatoidni arthritis, kombinirana terapija, reaktanti akutne fazeIntroductionIn clinical practice, the most common laboratory testing is erythrocytes sedimentation rate (ESR) accord-ing to Westergreen. In rheumatic infl ammatory diseas-es, ESR can be accelerated, which indicates the degree of infl ammation. In these diseases, the measurement of ESR helps to monitor the activity of disease and thera-peutic response. ESR can be accelerated in elderly, by anemia and hypercholesterolemia, in pregnancy and in kidney chronic failure. ESR can increase as a result of growing of fi brinogen and gamma-globulins. According to the current opinions, it the value for the fi rst hour of measure is enough (1).CRP increases 10-1000 times in the fi rst 5-10 hours and it is presented as response in bacterial process-es and in autoimmune diseases. Measurement of CRP concentration serves to monitor the activity of rheuma-toid arthritis and other autoimmune diseases. Fibrinogen is a weaker reactant during the acute phase; 24-48 hours after the necrosis of tissue its levels raise 2-3 times.In the acute phase of rheumatoid arthritis (RA), all infl ammatory parameters are positive. In the assess-ment of disease activity and monitoring of the disease it is suffi cient to measure ESR, the concentration of CRP and fi brinogen.prof.dr.sc. Sylejman RexhepiKodra e Diellit  Rr. II  Lamela 11/9  10000 Prishtina  Kosovophone: +381 38 557227  mobile: +377 44 14586478 Reumatizam 2009.  56(2)Disease-modifying antirheumatic drug (DMARDs) belong to the category of anti-rheumatics used in early stage of disease, which slow the progress of the disease and prevent injuries and disabilities by achieving normal-ization of optimal function of joints. DMARDs, including injectibile and oral form of gold therapy, hydroxychloro-chine sulphasalazine and methotrexate, have visible ef-fects. Normalization of ESR and CRP in most of the pa-tients is presented after 14 days, with disease remission after 1-2 months (44%), and complete improvement (in 45% of researched cases) (1). Treatment can start in the early phase and dosage should be individualized in ac-cordance with the patient’s tolerance and therapeutic re-sponse. Recently, methotrexate combined with sulphasala-zine and hydroxychloroquine has shown to be more ef-fective compared to the methotrexate therapy alone.Mechanism of DMARDs is unknown. Various authors have attempted to explain the results obtained through the elimination of immunocompetence lympho-cytes (1). Thus, immunosuppresion, as a result of the ac-tion of cytostatics, is clarifi ed by inhibition of the respon-sible cell and humoral immunity. During the application of DMARDs, authors noticed the reduction of ESR, CRP, fi -brinogen, as well as rheumatoid factor titer in serum, while the antiphlogystic action explains inhibition with the cre-ation of infl ammatory mediators (2). The best results are achieved if the usual dose is given. There are numerous side effects more frequent in the gastrointestinal system, alopecia, hemorrhagic cystitis, stomatitis, bacterial and mycosis infections, leucopenia, thrombocytopenia, while later side effects include hepatitis, azo- or oligospermia, fi brosis of the ovaries and malignant diseases (2).Objective of studyThe aim of the study was evaluation of the action of combined therapy in reactants in the acute phase and clinical symptoms in patients with rheumatoid arthritis. Hence, the purpose of study was the evaluation of drugs action that modifi es disease (DMARDs) on reactants in the acute phase: ESR, CRP and fi brinogen, while clinical parameters were followed by the number of swollen joints and the number of sensitive joints in palpation.Material and methodsIn this study, in the Clinical Rheumatologic De-partment, in group I 30 patients were investigated (24 women and 6 men) with rheumatoid arthritis, with age of 23-72 (average age 46) treated with the onset therapy (MTX); in group II 30 patients (23 women and 7 men) with age 21 to 69 (average age 45) that were treated with triple therapy (MTX, SSZ, HCQ).Patients involved in the study were part of the fi rst and second functional phase according to Steinbrocker, revised by ACR - American College of Rheumatology’s (1991) (3). Similarly, the majority of patients were in the fi rst and second anatomic phase of radiological changes.To all patients treated with DMARDs, conforming to the recommendations of the ACR (4), we conducted pre-therapeutic laboratory evaluation of the following pa-rameters: rheumatoid factor, the number of erythrocytes, leukocytes, platelets, red blood cell formula, enzymes and urine analysis. From the data of patient’s history, we have excluded the possibility of giving this medication to patients with any form of previous hepatitis. In the pre-therapeutic period, we did not have clinical indication for conducting of chest X-ray and lung functional tests.We have done further monitoring through laboratory tests, performed every 14 days. At this stage, we incorporated the tests: hematological analysis (erythrocytes, leukocytes, platelets), biochemical analysis (liver analysis and enzymes), urine analysis and functional lung tests every month.ESR, CRP and fi brinogen were tested at the begin-ning and at the end of treatment. For evaluation of the therapeutic effects subjective and objective parameters were used (average value of morning stiffness, grip of hands, and intensity of pain and average value of swell-ing). We used methodology of descriptive phase accord-ing to Likert for assessment of pain (5).We have done statistical analysis of the results we obtained through the structure indicators and estimates of arithmetic averages. We have identifi ed homogeneity set of statistics on the basis of these statistical parame-ters: the variation interval, standard deviation and coef-fi cient variation. We tested with the T-test of arithmetic averages for small dependent samples to fi nd the differ-ence between arithmetic average, and we tested with the χ2-test for no parametric data. All results obtained are presented in form of table.ResultsIn table 1, we have presented gender structure of patients in group I and II of the research study. In the overall structure of the cases involved in the research, in the group I there were more females than males (80% vs. 20%), and in group II more males than females (77% vs. 23%), which is a statistically signifi cant (p<0.003).The average age of patients in the group I was 42.90 years old, while in group II 47.20 years old.With the purpose of justifying the therapeutic effect of DMARDs, we followed subjective and objective param-eters and laboratory analysis (SE, PCR, and fi brinogen) be-fore and after the treatment, as presented in table 2.56(2)  Reumatizam 2009. 79Average value of morning stiffness for all patients was 68 to 72 minutes at the beginning of treatment. The average value morning stiffness at the end of treatment was 26 to 19 minutes. In testing average values, we found difference with important statistical signifi cance, respec-tive to the duration of morning stiffness between the two groups before and after treatment (p<0.01). Therefore, therapy with DMARDs has good effects, and triple ther-apy has very good therapeutic effect on the reducing the length of morning stiffness.The average value of grip of the hands to the pa-tients of two groups before treatment was 67 to 64 mm, while after the treatment was 84 to 94 mm. In testing the average values of this parameter before and after treat-ment, we also found signifi cant statistical difference (p<0.01). Triple therapy had much better therapeutic ef-fect in terms of increasing the grip of hands after treat-ment, compared to the onset therapy.Average value of swollen proximal interphalangeal joints also has improved. At the beginning of treatment the average was 70 to 68 mm, and at the end of treatment, the average was 64 to 61 mm. By testing the average values swollen in proximal interphalangeal joints before and after treatment we found signifi cant statistical difference (p<0.01) and with very good therapeutic effect of the triple therapy, in terms of reducing the swollen in PIF joints (table 2).The average value of ESR before treatment was 33 versus 38, and after treatment was 19 versus 14. In testing average values, we found signifi cant statistical difference regarding erythrocytes sedimentation rates values before and after treatment (p<0.01). Therapy with MTHX, CHQ and SSZ, in signifi cant way, has improved ESR. The av-erage value of PCR before treatment was 24 vs. 30, and after treatment was 12 versus 6. In testing average val-Table 1. Gender structure of patients in group I and IITablica 1. Podjela bolesnika po spolu unutar skupina I i IIGenderGroup I Group IINo. % No. %Male 6 20 7 23Female 24 80 23 77Total 30 100 30 100p<0.003Table 2. Average values of objective and subjective parametersTablica 2. Prosječne vrijednosti objektivnih i subjektivnih parametaraNo. ParametersBefore treatment After treatmentT-testI II I II1 Morning stiffness (min) 68 72 26 19 p<0.012 Grip of hands (mm) 67 64 84 94 p<0.013 Swollen in PIP joints (mm) 70 68 64 61 p<0.014 ERS 33 38 19 14 p<0.015 CRP 24 30 12 6 p<0.016 Fibrinogen 6.3 6.0 5.0 4.5 p<0.03Table 3. Structure of patients with rheumatoid arthritisaccording to pain intensityaccording to the descriptive phase of LikertTablica 3. Podjela bolesnika s reumatoidnim artritisomprema intenzitetu boli prema deskriptivnoj fazi LikertaPain Modality CodeBeforetreatmentAftertreatmentI II I IIWithout pain 0 0 0 8 12Light pain 1 15 10 13 12Medium pain 2 11 15 6 6Sever pain 3 4 5 3 0Extreme pain 4 0 0 0 0Total 30 30 30 30Table 4. Frequency of side effects in application of DMARDs (MTX, SSZ, HCQ)Tablica 4. Učestalost nuspojava u primjeni DMARD-a (MTX, SSZ, HCQ)Side effectsGroup I Group IINo % No %Leucopenia 2 10 3 15Thrombocytopenia 1 5 1 5Proteinuria 1 5 1 5Pruritus 1 5 1 5GI disorders (nausea, eructation, epigastric pain) 2 10 2 10With manifestations of side effects - subtotal 7 35 7 35Without manifestation of side effects 13 65 11 55Total 20 100 20 10080 Reumatizam 2009.  56(2)ues, we found signifi cant statistical difference between PCR values before and after treatment (p<0.001). Treat-ment with combined therapy has signifi cantly improved the PCR values in both groups, with a signifi cant differ-ence between group I and II (p<0.001).The average value of fi brinogen before treatment was 6.3 to 5.0, and after treatment was 6.0 to 4.5. In test-ing average values, we found signifi cant statistical dif-ference in the values of fi brinogen before and after treat-ment (p<0.03), and also combined therapy has improved fi brinogen values in the two investigated groups.The intensity of pain during treatment changed. Before treatment, all patients had light pain in the joints. (15 vs. 10), medium (11 vs. 15) and severe (4 vs. 5).After treatment, dose of onset and triple therapy is reduced gradually. After therapeutic treatment, pain as a symptom was eliminated in 8 to 12 patients. Severe pain have persistent (3 vs. 0), while larger structure consist-ing patients with light pain (13 vs. 12 cases) and medium pain with the same number (with 6 cases) (table 3).Side effects after taking DMARDs manifested only in 7 to 9 cases, of which leucopenia and gastro-intestinal disorders, were more frequent (2 to 3 cases) than nausea, eructation and epigastric pain, while one in one case we observed thrombocytopenia, proteinuria and pruritus (table 4).DiscussionConclusionsTherapy combined with DMARDs (MTX, SSZ, and HCQ) is preferable to the patients with rheuma-toid arthritis.General doses of MTX of 15 mg/weekly, SSZ 2-3 grams and HCQ from 400 mg give high improvements in subjective and objective parameters. Early infl amma-tory reactants (ESR, CRP and fi brinogen) have improved after the application of DMARDs. Gastrointestinal side effects, leucopenia, thrombocytopenia had transitory character, disappearing after temporary termination of methotrexate. DMARDs (MTX, SSZ, HCQ) were not stopped to any patient due to toxic action.Of the total number of 60 patients in both groups, in Group I were 24 females and 6 males, while in group II were 23 females and 7 males. This gender structure is consistent with other authors, who also found similar data, because as it is known, the disease attacks more women than men (6).Improvement of subjective and objective parame-ters: the morning stiffness (before treatment 69.5 minutes to 69.5 minutes, while after treatment 26 minutes to 21); grip of the hands (67 to 62, while after treatment 85 to 92), and the intensity of pain, which after treatment was reduced gradually (only two patients had severe pain, pain was eliminated in fi ve patients, while the pain was great-ly reduced to others), and other data is consistent with the data of other authors, who also after treatment with DMARDs, not in large doses, have achieved high results in the treatment of patients with rheumatoid arthritis (7,8). Parameters that have shown greatest improvement to our patients were grip of hands and morning stiffness, while swollen PIF joints has shown less improvement.Also, the average reduction in erythrocytes sed-imentations rate, PCR and fi brinogen before and af-ter treatment were statistically signifi cant, and the re-sults are consistent with the data of other authors. In our study, side effects were diverse from thrombocyto-penia, leucopenia, pruritus, as well as gastrointestinal side effects. These results are consistent with fi ndings of side effects even in the work of other authors (9,10,11).Literature1. Dürrigl T. Famakoterapija reumatoidnog artri-tisa. Medica Jadertina 1986;16(suppl):63-9.2. Izairi R. Principet bashkëkohore të mjekimit të artritit reumatoid. Praxis Medica 1987.3. Hochberg MC, Chane RW, Dwosh I, Lindsay S, Pin-cus T, Wolfe F. The American College of Rheumatology 1991 revised criteria for the classifi cation of global functional status in rheumatoid arthritis. Arthritis Rheum 1992;25:498-502.4. Kremer JM, Alercon GS, Lightfoot RW. Jr. et al. Methotrexate for rheumatoid arthritis. Suggested gu-idelines for monitoring liver toxicity. Arthritis Rheum 1994;37:316-28.5. Bellamy N. Pain measurement. In: Musculo-skeletal clinical metrology. Dordrecht: Kluwer Acade-mic Publishers. 1993:65-76.6. Jajić I. Klinička reumatologija. Zagreb: Medi-cinska knjiga. 1995:10-137.7. Konečni J. Klinička reumatologija. Beograd-Zagreb: Medicinska knjiga. 1984:153-268.8. Mc Carty DJ. Arthritis and Allied Conditions. Philadelphia: Lea and Febiger. 1985:785-97.9. Rexhepi S. Veçoritë e artritit reumatoid në pleqëri. Disertacion. Prishtinë: Universiteti i Prishtinës, 1997:34-53.10. Persellin RH. Treatment in Rheumatoid arthri-tis. In: Mc Carty DJ, red. Arthritis and Allied Conditions. Philadelphia: Lea and Febiger, 1985:643-59.11. Verhoeven A.C. Boers M., Tugwell P. Com-bination therapy in rheumatoid arthritis: updated syste-mic review. Br J Rheumat 1998;37:6129.

Učinci kombinirane terapije reumatoidnog artritisa na reaktante akutne faze

HRČAK - Portal of Croatian Scientific and Professional Journals

Učinci kombinirane terapije reumatoidnog artritisa na reaktante akutne faze

Abstract

Similar works

Full text

Available Versions

Hrčak - Portal of scientific journals of Croatia

HRČAK - Portal of Croatian Scientific and Professional Journals