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P24 Does folate deficiency contribute to MTX related adverse effects in rheumatoid arthritis patients in India
Abstracts of papers presented in IRACON-2010 P21 ESR or CRP, which inflammatory measure is accurate in rheumatoid arthritis? S Chandrashekara, KP Suresh, Renuka ChanRe Rheumatology and Immunology Center and ChanRe Diagnostic Laboratory, Bangaluru ESR and CRP are two commonly utilized laboratory parameters as measures of inflammation in many autoimmune diseases including RA. ESR is a nonspecific measure of inflammation as it measures the effect of proteins alteration on sedimentation process, whereas CRP represents one of the proteins responsive to inflammation. Tender joint count (TJC) and Swollen Joint Count (SJC) are two clinical measures which gives an approximate estimate of inflammation in RA, whereas other systemic non-articular component cannot be assessed by this. The TJC and SJC are time consuming and often influenced by observer bias. This study was undertaken to find out how much ESR and CRP as a test parameters, overlap with the TJC and SJC in a routine clinical practice. Material & Methods: 303 consecutive patients who are on regular follow-up in ChanRe RICR and diagnosed to have RA as per ACR criteria 1987 were included in the study. In a prospective analysis various core set measures of RA such as TJC, SJC in 66/64 joint count, VAS pain scale, ESR and CRP were recorded. The TJC and SJC were performed by independent joint assessor who has no control on treatment decision. Statistics: The data was analysed to find out the correlation between these measures using Spearmen correlation, congruity of ESR and CRP with TJC and SJC were analysed using mountain plot analysis. Result: 242 female and 61 male patients were included. The mean age was 46.8 years (17–79), duration of illness 70.81 (3–307) months and all were on conventional DMARD with majority on combination of methotrexate, Hydroxychloroquin and or leflunamide, with very few on other DMARD. TJC was 9.43 (0–30) and SJC 3.99 (0–39) and VAS 3.79 (0–10) with mean ESR 50.03 (SD 31.16) and CRP 10.50 (SD 19.43). Both ESR and CRP correlated with all three measures such as TJC, SJC and VAS. The correlation was stronger with ESR than CRP. When the effectiveness of ESR vs CRP was compared for replacement of the clinical parameters TJC and SJC by using mountain plot method, CRP performed better than ESR and coincided with both clinical parameters of the disease RA. Conclusion: The CRP is a better measure than ESR in following up the patients with RA, especially when the inflammation is the major focus of measurement, since it coincides more with other measures which do represent the inflammatory component of RA. If other possible causes of alteration in CRP are closely monitored before interpretation, result should improve the specificity of the measure.
P22 Comparison of clinical disease activity index (Indian version) with disease activity score-28 (DAS-28) in assessment of disease activity in rheumatoid arthritis (RA) patients H Singh, H Kumar, R Handa, P Talapatra, S Kumar, V Gupta Department of Medicine, Pt. BDS PGIMS, Rohtak Introduction: The goal in treatment of Rheumatoid Arthritis (RA) is to achieve remission and so objective assessment with composite index becomes imperative. Since DAS-28 requires complex calculations and use of acute phase reactants (i.e. ESR), so CDAI scoring appears more practical and validating cut off values as suggested by Arya & Malaviya (i.e. CDAIIndian version) should be useful. Methodology: A total of 200 patients of RA as per ACR-1987 criteria were taken and subjected to DAS-28 and CDAI (Indian version) score using their standard formula. All subjects depending upon their two scores were grouped into 4 categories i.e. Group-I: Remission (DAS-28 < 2.6; CDAI < 2.2), Group-II: low disease activity (DAS-28 = 2.6 to 3.2; CDAI = 2.2 to 5), Group-III: moderate disease activity (DAS-28 = 3.2 to 5.1; CDAI = 5 to 21), Group-IV: high disease activity (DAS-28 > 5.1; CDAI > 21). In each of these groups DAS-28 score was compared to CDAI groups using spearman correlation coefficient and kappa statistics. Results: the coparative values of DAS-28 score and CDAI in each group are as follows: Group-I show mean DAS-28 score of 1.99 ± 0.38; mean CDAI score of 0.90 ± 0.65, (p-value of < 0.0001). Group-II shows mean DAS-28 score of 3.04 ± 0.17; mean CDAI score of 4.17 ± 0.67, (p-value of 0.293). Group-III shows mean DAS-28 score of 4.25 ± 0.58; mean CDAI-B score of 13.97 ± 4.48 (p-value of < 0.0001). Group-IV shows mean DAS-28 score of 6.38 ± 0.87; mean CDAI score of 37.12 ± 12.10 (p-value of < 0.0001). Kappa statistics (k) of the above comparison was 0.699. Con nclusion: Our findings indicate that CDAI—a composite score that employs only clinical variables and omits assessment of APR, has similar validity to DAS-28 score for assessment of disease activity in RA patients. The suggested CDAI-Indian version’s value has a good correlation with DAS-28 and should be applied for evaluating disease activity in RA patients.
P23 Methotrexate induced pancytopenia: need for increased awareness amongst Primary care physicians
Poster presentations
S19
with methotrexate-induced pancytopenia seen between1996 and 2010 at the department of Immunology, Sanjay Gandhi Postgraduate institute of Medical Sciences, Lucknow. Methods: Patients were identified by departmental database search. Pancytopenia was defined as white blood cell count (WBC) < 3, 500 cells/mm3, hemoglobin (Hb) < 11 g/dl, platelet count < 1.5 lakh/mm3. Severe pancytopenia was defined as WBC < 2, 000 cells/mm3, Hb < 10 g/dl, platelet count < 50, 000 cells/mm3. Results: Fifteen patients had methotrexate induced pancytopenia (Female = 11). Eleven of these were under the care of either primary care physicians or orthopaedic surgeons and presented to our centre with cytopenia. Five patients had severe pancytopenia. The median age was 50 years (30 to 65). Nine had rheumatoid arthritis, 3 had psoriasis and one each with inflammatory bowel disease, systemic sclerosis and IgA nephropathy. The median cumulative dose was 277.5 mg (range 15 to 2640). The median dose of MTX was 10 mg per week (range 2.5 to 22.5 mg) and median duration of treatment 6.5 months (range 5 days to 66 months). All except 2 patients were receiving folate supplementation. Symptoms at presentation include; oral mucositis (n = 12); fever (n = 11); diarrhea, purpura and bleeding gums in 1 each. The number of patients with potential risk factors were: renal insufficiency (n = 3), hypoalbuminemia (n = 5), dosing errors (n = 3), elevated MCV (n = 9). Five patients died due to infections. All had severe pancytopenia. The pancytopenia recovered in the remaining 10 patients. The median time to recovery of cytopenia was 5 days (Range 3 to 11 days). Conclusions: In patients on Methotrexate, the symptoms of oral mucositis and fever can herald underlying cytopenia. Methotrexate-induced pancytopenia is associated with high mortality. There is need for increased awareness especially among primary care physicians, orthopaedic surgeons to minimise prescribing errors. It highlights the need for regular monitoring to avoid Methotrexate in patients with potential risk factors.
P24 Does folate deficiency contribute to MTX related adverse effects in rheumatoid arthritis patients in India Varun Dhir, Able Lawrence, Vikas Agarwal, MM Godbole, Amita Aggarwal Department of Immunology, Sanjay Gandhi Potgraduate Institute of Medical Science, Lucknow Background & Objective: Methotrexate remains the preferred DMARD in rheumatoid arthritis. Folate supplementation has been shown to reduce the adverse effects due to methotrexate, however, some patients are unable to tolerate MTX despite its use. We looked at the frequency of adverse effects due to methotrexate (MTX) in patients with rheumatoid arthritis (RA) on folate supplementation and to determine if there is any relationship with RBC folate levels. Methods: Cross-sectional study in university hospital in North India. Consecutive patients of rheumatoid arthritis on MTX (with or without other DMARDs) were enrolled. Adverse effects were identified and graded using a self administered questionnaire in Hindi or English. Included were nausea, vomiting, fatigue, headache, uneasiness, diarrhea, dizziness, skin rash, pruritus, loss of appetite and oral ulcers. Adverse effects were considered to be related to MTX if they were temporally related to the timing of weekly MTX dose (except oral ulcers). Abnormalities in Hb, TLC, platelets, SGOT, SGPT were also noted, but considered due to MTX only if patient was not on other DMARDs (except HCQ). In the case control arm of the study, RBC folate levels were measured in patients with (moderate-severe symptoms for at least 1 day or laboratory) and those without adverse effects by Chemiluminesence assay (Immulite, Siemens, UK). Statistical analysis was done using SPSS program: students t test and chi square test were used to compare means and proportions. Results: The study included 292 patients of rheumatoid arthritis on MTX with folate supplementation. Mean age was 46.4 yrs (SD 12.4) and female to male ratio was 5: 1. Mean disease duration was 8.6 yrs (SD 5.9) and 63% were RF positive. Of these 226 (77.4%) were only on MTX (with HCQ in 56% and with steroids in 30%), 15% were also on leflunomide and 6% also on sulfasalazine. Mean MTX dose was 17.3 mg (SD 4.3 mg) per week and mean folate dose was 10 mg (SD 3.1 mg) per week. Common adverse effects (symptoms) were nausea (21.8%), uneasiness (12.6%), fatigue (11.6%), vomiting (9.8%), headache (8.1%) and dizziness (6.5%). Anorexia, rash, pruritus and diarrhea occurred in less than 5%. Adverse effects (symptoms) to MTX were neither associated with mean dose of MTX nor the use of other DMARDs. Most common laboratory abnormality was transaminitis (SGOT or SGPT > 40) in 16.3% of the 226 patients on MTX or MTX + HCQS. Elevation to more than double (> 80) occurred in 3.1%. Thrombocytopenia (< 100, 000/cu mm) occurred in 2% and leucopenia (< 3500) in 0.9%. Transaminits was equally common in patients with and without symptoms due to MTX toxicity (16.9% vs17.6%). Patients with symptoms reduced or skipped their MTX dose more commonly than those without (19.6% vs 2.6%, p < 0001) and had higher disease activity [DAS 28–3: 4.2 (SD 1.3) vs 3.7 (SD 1.2), p = 0.002]. RBC folate levels were done in 27 patients with and 35 patients without adverse effects, and were not different (mean 569.8 (SD 311.6) vs 544.2 (SD 173.5) ng/ml, p = 0.25) in the two groups. Conclusions: Adverse effects due to MTX are common despite folate supplementation. These are unrelated to RBC folate levels, MTX dose and concomitant DMARDs. Patients with symptomatic adverse effects are more likely to miss/reduce their MTX thus leading to higher disease activity.
Yogesh Preet Singh, BN Shivaprasad, Amita Aggarwal, Able Lawrence, Ramnath Misra, Vikas Agarwal
P25 Self reported prevalence of rheumatological disease in a weaver dominated area in Varanasi
Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow
Amit Mehrotra, M Ozair, Rakhee Mehrotra
Background: Methotrexate (MTX) has gained wide acceptance among both patients and rheumatologists due to its efficacy and safe therapeutic window in a variety of rheumatological disorders. However, it has the potential to cause serious, life-threatening complications and even mortality. In this study we analyzed the predisposing factors and outcome in patients
Naman healthcare Rheumatology Centre, Varanasi Aim: A pilot study To determine the self reported prevalence of Rheumatological diseases in general population. and incidences of various major Rheumatological disease in a densely populated Weaver (bunker area in Varanasi.
P22 Comparison of clinical disease activity index (Indian version) with disease activity score-28 (DAS-28) in assessment of disease activity in rheumatoid arthritis (RA) patients H Singh, H Kumar, R Handa, P Talapatra, S Kumar, V Gupta Department of Medicine, Pt. BDS PGIMS, Rohtak Introduction: The goal in treatment of Rheumatoid Arthritis (RA) is to achieve remission and so objective assessment with composite index becomes imperative. Since DAS-28 requires complex calculations and use of acute phase reactants (i.e. ESR), so CDAI scoring appears more practical and validating cut off values as suggested by Arya & Malaviya (i.e. CDAIIndian version) should be useful. Methodology: A total of 200 patients of RA as per ACR-1987 criteria were taken and subjected to DAS-28 and CDAI (Indian version) score using their standard formula. All subjects depending upon their two scores were grouped into 4 categories i.e. Group-I: Remission (DAS-28 < 2.6; CDAI < 2.2), Group-II: low disease activity (DAS-28 = 2.6 to 3.2; CDAI = 2.2 to 5), Group-III: moderate disease activity (DAS-28 = 3.2 to 5.1; CDAI = 5 to 21), Group-IV: high disease activity (DAS-28 > 5.1; CDAI > 21). In each of these groups DAS-28 score was compared to CDAI groups using spearman correlation coefficient and kappa statistics. Results: the coparative values of DAS-28 score and CDAI in each group are as follows: Group-I show mean DAS-28 score of 1.99 ± 0.38; mean CDAI score of 0.90 ± 0.65, (p-value of < 0.0001). Group-II shows mean DAS-28 score of 3.04 ± 0.17; mean CDAI score of 4.17 ± 0.67, (p-value of 0.293). Group-III shows mean DAS-28 score of 4.25 ± 0.58; mean CDAI-B score of 13.97 ± 4.48 (p-value of < 0.0001). Group-IV shows mean DAS-28 score of 6.38 ± 0.87; mean CDAI score of 37.12 ± 12.10 (p-value of < 0.0001). Kappa statistics (k) of the above comparison was 0.699. Con nclusion: Our findings indicate that CDAI—a composite score that employs only clinical variables and omits assessment of APR, has similar validity to DAS-28 score for assessment of disease activity in RA patients. The suggested CDAI-Indian version’s value has a good correlation with DAS-28 and should be applied for evaluating disease activity in RA patients.
P23 Methotrexate induced pancytopenia: need for increased awareness amongst Primary care physicians
Poster presentations
S19
with methotrexate-induced pancytopenia seen between1996 and 2010 at the department of Immunology, Sanjay Gandhi Postgraduate institute of Medical Sciences, Lucknow. Methods: Patients were identified by departmental database search. Pancytopenia was defined as white blood cell count (WBC) < 3, 500 cells/mm3, hemoglobin (Hb) < 11 g/dl, platelet count < 1.5 lakh/mm3. Severe pancytopenia was defined as WBC < 2, 000 cells/mm3, Hb < 10 g/dl, platelet count < 50, 000 cells/mm3. Results: Fifteen patients had methotrexate induced pancytopenia (Female = 11). Eleven of these were under the care of either primary care physicians or orthopaedic surgeons and presented to our centre with cytopenia. Five patients had severe pancytopenia. The median age was 50 years (30 to 65). Nine had rheumatoid arthritis, 3 had psoriasis and one each with inflammatory bowel disease, systemic sclerosis and IgA nephropathy. The median cumulative dose was 277.5 mg (range 15 to 2640). The median dose of MTX was 10 mg per week (range 2.5 to 22.5 mg) and median duration of treatment 6.5 months (range 5 days to 66 months). All except 2 patients were receiving folate supplementation. Symptoms at presentation include; oral mucositis (n = 12); fever (n = 11); diarrhea, purpura and bleeding gums in 1 each. The number of patients with potential risk factors were: renal insufficiency (n = 3), hypoalbuminemia (n = 5), dosing errors (n = 3), elevated MCV (n = 9). Five patients died due to infections. All had severe pancytopenia. The pancytopenia recovered in the remaining 10 patients. The median time to recovery of cytopenia was 5 days (Range 3 to 11 days). Conclusions: In patients on Methotrexate, the symptoms of oral mucositis and fever can herald underlying cytopenia. Methotrexate-induced pancytopenia is associated with high mortality. There is need for increased awareness especially among primary care physicians, orthopaedic surgeons to minimise prescribing errors. It highlights the need for regular monitoring to avoid Methotrexate in patients with potential risk factors.
P24 Does folate deficiency contribute to MTX related adverse effects in rheumatoid arthritis patients in India Varun Dhir, Able Lawrence, Vikas Agarwal, MM Godbole, Amita Aggarwal Department of Immunology, Sanjay Gandhi Potgraduate Institute of Medical Science, Lucknow Background & Objective: Methotrexate remains the preferred DMARD in rheumatoid arthritis. Folate supplementation has been shown to reduce the adverse effects due to methotrexate, however, some patients are unable to tolerate MTX despite its use. We looked at the frequency of adverse effects due to methotrexate (MTX) in patients with rheumatoid arthritis (RA) on folate supplementation and to determine if there is any relationship with RBC folate levels. Methods: Cross-sectional study in university hospital in North India. Consecutive patients of rheumatoid arthritis on MTX (with or without other DMARDs) were enrolled. Adverse effects were identified and graded using a self administered questionnaire in Hindi or English. Included were nausea, vomiting, fatigue, headache, uneasiness, diarrhea, dizziness, skin rash, pruritus, loss of appetite and oral ulcers. Adverse effects were considered to be related to MTX if they were temporally related to the timing of weekly MTX dose (except oral ulcers). Abnormalities in Hb, TLC, platelets, SGOT, SGPT were also noted, but considered due to MTX only if patient was not on other DMARDs (except HCQ). In the case control arm of the study, RBC folate levels were measured in patients with (moderate-severe symptoms for at least 1 day or laboratory) and those without adverse effects by Chemiluminesence assay (Immulite, Siemens, UK). Statistical analysis was done using SPSS program: students t test and chi square test were used to compare means and proportions. Results: The study included 292 patients of rheumatoid arthritis on MTX with folate supplementation. Mean age was 46.4 yrs (SD 12.4) and female to male ratio was 5: 1. Mean disease duration was 8.6 yrs (SD 5.9) and 63% were RF positive. Of these 226 (77.4%) were only on MTX (with HCQ in 56% and with steroids in 30%), 15% were also on leflunomide and 6% also on sulfasalazine. Mean MTX dose was 17.3 mg (SD 4.3 mg) per week and mean folate dose was 10 mg (SD 3.1 mg) per week. Common adverse effects (symptoms) were nausea (21.8%), uneasiness (12.6%), fatigue (11.6%), vomiting (9.8%), headache (8.1%) and dizziness (6.5%). Anorexia, rash, pruritus and diarrhea occurred in less than 5%. Adverse effects (symptoms) to MTX were neither associated with mean dose of MTX nor the use of other DMARDs. Most common laboratory abnormality was transaminitis (SGOT or SGPT > 40) in 16.3% of the 226 patients on MTX or MTX + HCQS. Elevation to more than double (> 80) occurred in 3.1%. Thrombocytopenia (< 100, 000/cu mm) occurred in 2% and leucopenia (< 3500) in 0.9%. Transaminits was equally common in patients with and without symptoms due to MTX toxicity (16.9% vs17.6%). Patients with symptoms reduced or skipped their MTX dose more commonly than those without (19.6% vs 2.6%, p < 0001) and had higher disease activity [DAS 28–3: 4.2 (SD 1.3) vs 3.7 (SD 1.2), p = 0.002]. RBC folate levels were done in 27 patients with and 35 patients without adverse effects, and were not different (mean 569.8 (SD 311.6) vs 544.2 (SD 173.5) ng/ml, p = 0.25) in the two groups. Conclusions: Adverse effects due to MTX are common despite folate supplementation. These are unrelated to RBC folate levels, MTX dose and concomitant DMARDs. Patients with symptomatic adverse effects are more likely to miss/reduce their MTX thus leading to higher disease activity.
Yogesh Preet Singh, BN Shivaprasad, Amita Aggarwal, Able Lawrence, Ramnath Misra, Vikas Agarwal
P25 Self reported prevalence of rheumatological disease in a weaver dominated area in Varanasi
Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow
Amit Mehrotra, M Ozair, Rakhee Mehrotra
Background: Methotrexate (MTX) has gained wide acceptance among both patients and rheumatologists due to its efficacy and safe therapeutic window in a variety of rheumatological disorders. However, it has the potential to cause serious, life-threatening complications and even mortality. In this study we analyzed the predisposing factors and outcome in patients
Naman healthcare Rheumatology Centre, Varanasi Aim: A pilot study To determine the self reported prevalence of Rheumatological diseases in general population. and incidences of various major Rheumatological disease in a densely populated Weaver (bunker area in Varanasi.