scholarly journals β-cell Related Amyloidosis Localized to the Islets of Langerhans, Type II Diabetes Mellitus and Liponecrotic Pancreatitis in Rheumatoid Arthritis: A Postmortem Clinicopathologic Statistical Study of 234 Autopsy Patients

2019 ◽  
pp. 94-110
Author(s):  
Bély M ◽  
Apáthy A
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Islets Of Langerhans ◽  
Early Stage ◽  
Type Ii Diabetes Mellitus ◽  
Biopsy Material ◽  
Tissue Samples ◽  
American College Of Rheumatology ◽  
Significant Difference ◽  
Chi Squared

The aim of this study was to determine the prevalence of systemic AA amyloidosis (AAa), islet amyloidosis (IA) and liponecrotic pancreatitis (LnP) including acute liponecrotic (aLnP), acute relapsing liponecrotic (aRelLnP), and chronic liponecrotic pancreatitis (chrLnP) in rheumatoid arthritis (RA), and to analyse the possible relationship between them.Patients and methods: At the National Institute of Rheumatology 11558 patients died between 1969 and 1998; among them 234 with RA, and all of them were autopsied. RA was confirmed clinically according to the criteria of the American College of Rheumatology (ACR). The diagnosis of DM was based on clinical data. Tissue samples of pancreas were available for histologic evaluation in 164 of 234 patients. AAa, IA and LnP were diagnosed histologically. Demographics of different patient cohorts were compared with the Student (Welch) t probe. The relationships between AAa and IA, furthermore between IA and DM or LnP (including aLnP, aRelLnP, chrLnP) were analyzed by Pearson’s chi-squared (c2) test.Results: AAa complicated RA in 42 (25.61%) of 164 patients. IA localized to the islets of Langerhans was observed in 16 (9.76%) of 164 pancreases. Clinically diagnosed DM was associated with RA in 31 (18.90%) of 164 patients. Pancreatitis with multiple liponecrotic foci (LnP) was found in 19 (11.58%) of 164 patients; aLnP existed in 9 (47.37%), aRelLnP in 4 (21.05%), and liponecrotic foci in combination with chronic fibrotic pancreatitis (chrLnP) in 6 (31.58%) of these 19 patients.Discussion and conclusions: There was no significant difference between female and male RA patients associated with AAa, IA, DM and LnP. The age, sex and onset of disease did not influence basically the prevalence of AAa, IA, DM and LnP except male patients with IA, whose mean age at death was significantly higher than the general RA population. IA (fibrillar amyloid IAPP deposits -AIAPP) is related to the activity of b cells and may presumably be a faulty product of b-cells (normal islets of Langerhans do not contain IA deposits). The progressive deposition of IAPP prohormon fragments inhibits the function of b-cells because of their toxic effect and/or blocking mechanically the blood supply of b-cells and they “die in their own product”. The significant correlation between IA and DM refers to a close connection between them, but not necessarily a direct cause and effect relationship; it may be an indirect result of damaged (apoptotic) b-cells. The early stage of IA is characterized by minimal IAPP deposits involving only a few islets, which represents a clinically latent DM, and the advanced stage of IA is characterized by massive IAPP deposits involving most of the islets, which correspond to clinically manifest DM. Based on the positive and significant correlation between IA and clinically not diagnosed DM, IA may be a good indicator of potential DM in the latent stage of disease. Therefore we recommend that all biopsy material and surgical specimens of pancreas to be tested for IA or IAPP deposition.

scholarly journals Periodontal disease and influence of periodontal treatment on disease activity in patients with rheumatoid arthritis and spondyloarthritis

2019 ◽  
Vol 40 (3) ◽  
pp. 455-463 ◽  
Author(s):  
Katarzyna Białowąs ◽  
Małgorzata Radwan-Oczko ◽  
Irena Duś-Ilnicka ◽  
Lucyna Korman ◽  
Jerzy Świerkot
Keyword(s):  
Rheumatoid Arthritis ◽  
Periodontal Disease ◽  
Disease Activity ◽  
Early Stage ◽  
Periodontal Treatment ◽  
Number Of Teeth ◽  
Probing Depth ◽  
Significant Difference ◽  
Polymerase Chain ◽  
Oral Hygiene Instructions

Abstract The aim of this study was to assess the prevalence of periodontal disease and the effect of periodontal treatment in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). Forty-four RA patients, thirty SpA patients and thirty-nine healthy volunteers were recruited to the study. Periodontal examination included the approximal plaque index (API), bleeding on probing (BoP), probing depth (PD) and number of teeth. Samples from the deepest periodontal pockets were taken for the detection of Porphyromonas gingivalis DNA with the use of the polymerase chain reaction. All subjects with periodontitis, who completed the study, received periodontal treatment consisting of scaling/root planing and oral hygiene instructions. Disease activity scores, clinical and laboratory parameters were assessed before and 4–6 weeks after periodontal treatment. No significant difference in the prevalence of periodontal disease and the presence of P. gingivalis DNA were found in RA and SpA patients compared to healthy controls. Significantly higher API (80% vs 63%; p = 0.01) and a lower number of teeth (20 vs 25, p = 0.001) were found in RA patients. BoP was significantly elevated in SpA patients (51% vs 33%, p = 0.02). Disease activity measured by the DAS28(CRP) was significantly reduced in RA patients after periodontal treatment (p = 0.002). Clinical and biochemical parameters were not improved in SpA patients. Nonsurgical periodontal treatment had an impact on the decrease in RA activity. Periodontal examination is necessary in patients with RA to detect and treat periodontitis at an early stage.

Prognostic Significance of BCL-2 Expression in Localized Squamous Cell Carcinoma of the Head and Neck

1997 ◽  
Vol 106 (6) ◽  
pp. 445-450 ◽  
Author(s):  
Philip Grey ◽  
Prashant Chawla ◽  
Michael Friedman ◽  
T. K. Venkatesan ◽  
David D. Caldarelli ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Early Stage ◽  
Prognostic Significance ◽  
Second Primary ◽  
Tissue Samples ◽  
Poor Outcome ◽  
Significant Difference

This study was conducted to determine whether Bcl-2 overexpression in localized squamous cell carcinoma of the head and neck (SCCHN) might serve as a marker for tumors unlikely to respond to standard treatment. Tissue samples from 33 patients undergoing surgery or irradiation for early-stage SCCHN during the years 1977 to 1992 were stained for Bcl-2. All patients had either T1N0 lesions of the oral cavity, pharynx, or larynx or T1 NO or T2N0 lesions of the true vocal cords. Of the 33 patients, 26 remained disease-free after at least 3 years of follow-up; the remaining 7 patients developed either tumor recurrence or a second primary tumor, 4 of which were fatal. Twelve patients had tissue specimens staining positive for Bcl-2; 6 of these patients had a poor outcome, and 6 had a good outcome. The relationship between poor outcome and overexpression of Bcl-2 in tumor cells was statistically significant (p =.0047 by Fisher's exact test). For tumors overexpressing Bcl-2, there was no significant difference in recurrence rate between those undergoing surgery and those undergoing radiotherapy as the primary mode of treatment. The overexpression of Bcl-2 in early lesions in this study predicted a cure rate of 50%, as opposed to the generally expected 90%, suggesting that Bcl-2 is a significant prognostic indicator in early SCCHN. Future studies will determine if altering the treatment will improve outcome in these patients.

B-cell-activating factor receptor expression on naive and memory B cells: relationship with relapse in patients with rheumatoid arthritis following B-cell depletion therapy

2010 ◽  
Vol 69 (12) ◽  
pp. 2181-2188 ◽  
Author(s):  
Inmaculada de la Torre ◽  
Rita A Moura ◽  
Maria J Leandro ◽  
Jonathan Edwards ◽  
Geraldine Cambridge
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Receptor Expression ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
B Cell Activating Factor ◽  
Significant Difference ◽  
Cell Repopulation

ObjectivesTo examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27− and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab.Patients and MethodsBAFF-R expression on B-cell subsets was determined in normal controls (NC; n=11), active patients with RA pre-rituximab (pre-RX; n=15), relapsing patients either concordant for B-cell repopulation (C-R, n=13) or discordant, with relapse more than 3 months after repopulation (D-R, n=11) and patients in remission over 3 months postrepopulation (discordant non-relapsing (D-NR), n=5). Serum BAFF was measured by ELISA and analysed using Mann–Whitney.ResultsThere was no significant difference between NC, pre-RX and D-NR patients in %BAFF-R-positive B cells or mean fluorescence intensity (MFI) in naive and memory B cells. Relapsing patients had significantly lower MFI and %BAFF-R-positive cells in both naive and memory compartments from NC and pre-RX (C-R and D-R; p<0.01). BAFF levels in pre-RX patients were within the normal range and did not correlate with BAFF-R expression in any patient group. D-NR patients had relatively lower proportions of pre and postswitch CD27+ B cells than pre-RX patients (D-NR vs pre-RX; p<0.05 for both) and also lower numbers of postswitch B cells than D-R patients (D-NR vs D-R, p<0.05).ConclusionBAFF-R expression was significantly reduced on both naive and memory B cells in patients at relapse, regardless of the relationship with B-cell repopulation or serum BAFF levels. Re-establishment of active disease was also associated with an increase in class-switch recombination. Factors responsible for lower levels of BAFF-R may relate to altered thresholds for autoreactive B-cell generation at relapse in patients with RA.

The New Use of an Ancient Remedy: A Double-Blinded Randomized Study on the Treatment of Rheumatoid Arthritis

2013 ◽  
Vol 41 (02) ◽  
pp. 263-280 ◽  
Author(s):  
Letian Chen ◽  
Haiyu Qi ◽  
Dezhen Jiang ◽  
Renshuo Wang ◽  
Aidong Chen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Randomized Study ◽  
Chronic Inflammatory Disease ◽  
Onset Of Action ◽  
End Point ◽  
American College Of Rheumatology ◽  
Significant Difference ◽  
Blinded Study ◽  
Maximum Improvement ◽  
Double Blinded

Rheumatoid arthritis (RA) is the most common chronic inflammatory disease with unknown causes and unknown cures in Western medicine. This double-blinded study aimed to investigate the efficacy and safety of a widely used traditional Chinese medicine (Paeoniflorin (PAE) plus cervus and cucumis polypeptide injection (CCPI) using disease-modifying antirheumatic drugs (DMARD) as a control (methotrexate (MTX) plus leflunomide (LEF)). Patients were randomly assigned to one of the three groups: PAE + CCPI, MTX + LEF, and MTX + LEF + CCPI. The primary end point was the American College of Rheumatology 20% improvement response criteria (ACR20). The secondary end point was that of adverse effect frequencies and the speed of onset action. Our results showed that more patients in the CCPI-containing groups responded to the ACR20 during early treatment. After six months, ACR20 showed no significant difference among the three treatments. The maximum improvement in the two DMARD groups was significantly higher than that in the PAE + CCPI group (p < 0.01). CCPI made the onset action of the DMARD therapy 4.6 times faster. PAE + CCPI had significantly lower adverse event incidences than the two DMARD groups. These results indicate that PAE + CCPI appear to be a more acceptable alternative to DMARDs when patients cannot use DMARDs. CCPI appears to be a beneficial add-on to DMARDs that makes the onset of action faster, especially when patients need to relieve RA symptoms as soon as possible. Although not as effective as DMARDs, PAE appears to be a safer option to substitute DMARDs for long-term RA treatment when DMARD toxicity is an issue.

scholarly journals ARG2, MAP4K5 and TSTA3 as Diagnostic Markers of Steroid-Induced Osteonecrosis of the Femoral Head and Their Correlation With Immune Infiltration

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongguo Yu ◽  
Jiayu Zhang ◽  
Youguang Zhuo ◽  
Xu Hong ◽  
Jie Ye ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
Femoral Head ◽  
Immune Cells ◽  
Early Stage ◽  
Diagnostic Markers ◽  
Memory B Cells ◽  
Qrt Pcr ◽  
Significant Difference ◽  
The Relationship

BackgroundThe diagnosis for steroid-induced osteonecrosis of the femoral head (SONFH) is hard to achieve at the early stage, which results in patients receiving ineffective treatment options and a poor prognosis for most cases. The present study aimed to find potential diagnostic markers of SONFH and analyze the effect exerted by infiltration of immune cells in this pathology.Materials and MethodsR software was adopted for identifying differentially expressed genes (DEGs) and conducting functional investigation based on the microarray dataset. Then we combined SVM-RFE, WGCNA, LASSO logistic regression, and random forest (RF) algorithms for screening the diagnostic markers of SONFH and further verification by qRT-PCR. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. CIBERSORT was then adopted for assessing the infiltration of immune cells and the relationship of infiltration-related immune cells and diagnostic markers.ResultsWe identified 383 DEGs overall. This study found ARG2, MAP4K5, and TSTA3 (AUC = 0.980) to be diagnostic markers of SONFH. The results of qRT-PCR showed a statistically significant difference in all markers. Analysis of infiltration of immune cells indicated that neutrophils, activated dendritic cells and memory B cells were likely to show the relationship with SONFH occurrence and progress. Additionally, all diagnostic markers had different degrees of correlation with T cell follicular helper, neutrophils, memory B cells, and activated dendritic cells.ConclusionARG2, MAP4K5, and TSTA3 are potential diagnostic genes for SONFH, and infiltration of immune cells may critically impact SONFH occurrence and progression.

scholarly journals FRI0065 CLINICAL FEATURES OF METHOTREXATE ASSOCIATED LYMPHOPROLIFERATIVE DISORDER IN RHEUMATOID ARTHRITIS PATIENTS AND INFLUENCE OF CD8 POSITIVE LYMPHOCYTE INFILTRATION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 609.2-609
Author(s):  
T. Kameda ◽  
S. Nakashima ◽  
M. Inoo ◽  
I. Onishi ◽  
N. Kurata ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Symptom ◽  
Clinical Features ◽  
Laboratory Data ◽  
Histological Finding ◽  
B Cell Lymphoma ◽  
Classification Criteria ◽  
Lymphocyte Infiltration ◽  
American College Of Rheumatology ◽  
Significant Difference

Background:Lymphoproliferative disorders (LPD) that develop in rheumatoid arthritis (RA) patients treated with MTX (MTX-LPD) is one of the important complications for RA patients. We have previously epidemiologically demonstrated an association between MTX and the development of LPD in RA patients1). MTX-LPD has varied pathologies including various clinical symptom and histological finding. Therefore, we need more information about MTX-LPD. In addition, it is one of the characteristics for MTX-LPD that spontaneous regression (SR) after MTX discontinuation. However, the mechanism of SR is not clarified.Objectives:We collect the information such as clinical symptom and histological finding of MTX-LPD with RA patients, and clarify the clinical features of MTX-LPD. In addition, we investigated the difference between SR cases and cases that treated with chemotherapy after MTX discontinuation (CTx cases).Methods:We enrolled 90 MTX-LPD patients from Kagawa Prefecture, Japan between June 2005 and December 2019. Patients were diagnosed according to American College of Rheumatology (ACR) 1987 classification criteria or ACR/European League Against Rheumatism (EULAR) 2010 classification criteria, and treated with disease modifying antirheumatic drugs (DMARDs) including MTX. We collected as follow information; age, gender, duration of RA, laboratory data (lymphocyte counts and sIL-2R) and treatment of MTX-LPD. In addition, we divided 16 MTX-LPD cases diagnosed histological into two groups (SR:CTx group; n=10:6), and analyzed the histological findings (CD4, CD8, CD163 and CD47) using the staining in immunohistochemistry (IHC) between the two groups. Each positive cell analyzed using virtual viewer soft ImageScope.Results:Characteristics of 90 MTX-LPD patients are as follow; mean age 66.5±11.2 years,63 female, duration of RA 18.5±19.4 years. 65 patients (72.2%) were spontaneously improved by discontinuing MTX. 58 patients (64.4%) were proven MTX-LPD histologically. In these patients, diffuse large B-cell lymphoma (DLBCL) was the most frequent histological type of MTX-LPD (56.9%). Infiltration of CD8 positive lymphocyte in the lesion was significant less in the SR cases than in the CTx cases (Figure 1). However, CD4, CD163 and CD47 positive cells had no significant difference between two groups.Figure 1.CD8 positive lymphocytes in the specimen of lesion using the staining in immunohistochemistry (IHC) between SR and CTxgroup.Conclusion:We revealed clinical features of MTX-LPD with RA patients. In addition, CD8 positive lymphocytes are involved in tumor immunity. In this study, we suggested that the extent of CD8 positive lymphocyte infiltration may predict SR of MTX-LPD. Further study is necessary on revealing the mechanism of SR in MTX-LPD.References:[1]Kameda T. et al. Arthritis Care Res (Hoboken). 2014 Sep;66(9):1302-9.Disclosure of Interests:None declared

Evaluation of Some Immunological Marker for Early Diagnosis of Rheumatoid Arthritis

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Israa K AL- Yasiri ◽  
Israa K AL- Yasiri ◽  
Jaafar K Al-Mousawi ◽  
Ali M.Al Mohana
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Interleukin 1 ◽  
Joint Damage ◽  
Serological Marker ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Significant Difference ◽  
Healthy Control

Rheumatoid arthritis (RA) is a chronic,destructive autoimmune disease affecting the joints. With more sophisticated and effective therapies becoming available and with the understanding that early intervention is crucial in preventing irreversible joint damage,it is more and more important to diagnose RA at a very early stage in the disease. To facilitate diagnosis during the early stages of the disease,when often not all clinical symptoms are manifest,a good serological marker is needed. The main purpose of this observational study was to evaluate and detects a good serological marker and genetic factors may be used in early detection of RA. This study covers quite different regions of Najaf province,including rural and urban communities. During the period from May 2010 to May2011,a total of 40 patients with RA who were fulfilled four or more of the 1987 American College of Rheumatology (ACR),20 patients with joints problems (JP),20 RA patient relatives (PR) and 10 apparently healthy control individuals were included in this study. Cytokines (interleukin-1,IL-6,IL-10 and TNF ɑ),antibodies directed to cyclic citrullinated peptide (anti-CCP3),and anti-human immunoglobulin binding protein (anti-BiP) antibodies in the human serum samples were measured by enzyme-linked immunosorbent assay (ELISA). Thirty-two RA patients (80.0%) were positive for anti-CCP3,whereas only 20.0%,30.0% and 0.0% showed a positive reaction,in particular sera from PR,JP and healthy control,respectively with highly significant difference was observed. The mean serum anti-CCP3 antibody level was higher in RA patients than in other groups. The anti-BiP antibody levels were significantly increased in RA patients than in PR and healthy control. However,the levels of anti-BiP antibody were slightly increased in the JP and no significant difference was detected between RA patients and JP. Analysis of the serum samples showed that concentrations of the Proinflammatory cytokines,IL-1,IL-6 and TNFɑ were significantly increased in RA patients compared with matched control subjects. While,The level of IL-10 was significantly lower for RA patients than for healthy Control cases.

scholarly journals Allied Disorders and Complications of Rheumatoid Arthritis - A Statistical Comorbidity Study of 234 Autopsy Patients

2019 ◽  
Vol 3 (1) ◽  
pp. 1-15
Author(s):  
Miklos Bely
Keyword(s):  
Rheumatoid Arthritis ◽  
Positive Influence ◽  
Cardiac Insufficiency ◽  
Malignant Tumours ◽  
Lethal Outcome ◽  
American College Of Rheumatology ◽  
Increased Risk ◽  
Chi Squared ◽  
Septic Vasculitis

Objective : The incidence of co - morbidities is higher in rheumatoid arthritis (RA) than in the general population. Associated diseases accompanying RA may modify the clinical course and symptoms of RA and may influence the prevalence and mortality of complications related to the basic diseases and vica versa. The aim of this study was t o determine statistically the possible effect of certain allied disorders: type 2 diabetes mellitus (DM), atherosclerosis (Ath) , hypertension (HT), tuberculosis (Tb) with miliary dissemination (mTb), and malignant tumours (mTu) on the prevalence and mortal ity of RA related complications: systemic autoimmune vasculitis (AV), AA amyloidosis (AAa), lethal cardiac insufficiency (CI) caused by endo - , myo - or pancarditis, with or without interstitial pneumonitis, furthermore lethal septic infection (SI) combined with septic vasculitis (SV) or purulent arthritis (PA) Patients a nd Methods : Twohundred thirty four (234) non - selected autopsy patients with RA were studied. RA was confirmed clinically according to the criteria of the American College of Rheumatology (A CR). The presence of DM, Ath, HT, Tb, mTb, or mTu was determined and analyzed retrospectively, reviewing the clinical and pathological reports. The prevalence and mortality of AV, AAa, CI, SI, SV and PA was determined at autopsy and confirmed by a detailed review of extensive histological material. Demographics of different patient cohorts were compared with the Student (Welch) t - probe. The link between Ath, HT, DM, Tb, mTb, or mTu and AV, AAa, CI, SI, SV or PA was analyzed by Pearson's chi - squared (χ2) tes t. Results : RA associated with DM in 41 (17.52%), with severe Ath in 107 (45.72%), with HT in 41 (17.52%), with with Tb in 28 (11.96%), including active disseminated mTb in 9 (3.85%), and with mTu in 27 (11.54%) of 234 patients. RA was complicated by AV in 43 (18.38 %), by AAa in 48 (20.51%), by CI in 15 (6.41%), and by lethal SI in 33 (14.10%) of 234 patients. SI was combined with PA in 15 (6.41% of 234; 45.45% of 33) or with SV in 7 (2.99% of 234; 21.21% of 33) patients; PA or SV did not occur without gen eralized SI. The relationship between Ath and AV, AV (lethal), AAa, AAa (lethal), CI, SI, PA or SV was consequently inverse and mostly significant. There was a positive and significant correlation between Tb or mTb and AV, furthermore between mTb and mortality of AV. Discussion and Conclusions : The consequently inverse and (in most cases) significant correlation between atherosclerosis and autoimmune vasculitis, amyloidosis or sepsis shows that the prevalence or mortality of AV, AAa and SI wa s not influenced by Ath. RA patients with Ath may represent a special group, characterized by lower incidence of SV, AAa, SI, CI, and carry a better prognosis. Ath is basically an age - dependent phenomenon, characteristically present in RA patients with adv anced age, while AV, AAa (with or without lethal outcome) and SI are complications of RA, and characterize severe forms of disease, mostly in younger patients and with an earlier onset (without pronounced atherosclerosis). The positive and significant corr elation between Tb or mTb and AV suggest a positive influence of Tb or mTb on the prevalence of vasculitis, e.g. the presence of Tb or endogenous exacerbation and miliary dissemination of Tb may promote the AV. The significant connection between mTb and mo rtality of AV indicates an increased risk of lethal outcome.

scholarly journals Efficacy of doxycycline as a combination therapy in the treatment of rheumatoid arthritis: a randomized controlled clinical trial

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Eman M. Ibrahem ◽  
Salwa S. El-gendi ◽  
Amal A. Mahmoud ◽  
Sherif M. Abdel-Aal ◽  
Hanan Sharaf El-Deen Mohammed
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Combination Therapy ◽  
Cost Effective ◽  
Controlled Clinical Trial ◽  
Open Label ◽  
American College Of Rheumatology ◽  
Effective Combination ◽  
Number Of Patients ◽  
Significant Difference

Abstract Background This single-center randomized open-label clinical trial evaluates the effectiveness of doxycycline as a combination therapy for active rheumatoid arthritis (RA) with methotrexate (MTX). Materials and methods One hundred and sixty RA patients were recruited who fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Subjects were randomly allocated in a 1:1 ratio into one of two treatment arms; one group was maintained on MTX alone and the other group on MTX together with doxycycline orally 200 mg daily. Follow-up clinical response, erythrocyte sedimentation rate (ESR), levels of C-reactive protein (CRP), and disease activity score 28 (DAS28-CRP) after 3 months were done. Results There was a significant difference regarding DAS28-CRP between the two groups (median (IQR) 4.26 (3.6–5) for those treated with MTX alone compared with 2.8 (2.37–3.5) for those treated with MTX together with doxycycline) (p = 0.005). A higher number of patients treated with doxycycline in combination with MTX achieved remission (40.5%) compared to patients who received MTX alone (13.5%). The levels of ESR and CRP were lower in patients treated with MTX and doxycycline and this was statistically significant (p = 0.005, p = 0.003 respectively). Conclusion Doxycycline as a cost-effective combination therapy with MTX can achieve higher rates of remission than MTX alone in RA patients without causing increase in the adverse events profile. Trial registration Clinical Trials.gov, NCT03194204. Registered on 21 June 2017

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