Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: a retrospective review of 15 cases and analysis of risk factors

Objectives

The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy.

Methods

We conducted a multicenter, case–control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy.

Results

PCP developed within 26?weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥65?years [hazard ratio (HR) 3.35, p?=?0.037], coexisting lung disease (HR 4.48, p?=?0.009), and concomitant methotrexate treatment (HR 4.68, p?=?0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p?<?0.001 for patients with two or more risk factors vs. those with no risk factor, and p?=?0.001 for patients with one risk factor vs. those with no risk factor).

Conclusion

Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.     

Efficacy of adjunct tacrolimus treatment in patients with rheumatoid arthritis with inadequate responses to methotrexate

Abstract

Objectives We aimed to assess the efficacy of tacrolimus (TAC) as an add-on therapy in patients with rheumatoid arthritis (RA) who were previously treated with methotrexate (MTX) but not with biologics.

Methods The study group (MTX + TAC group) consisted of 157 patients (selected from among the patients in the Institute of Rheumatology, Rheumatoid Arthritis [IORRA] RA cohort from April 2005 to October 2009) who received add-on therapy with TAC in addition to MTX, but without biologics. A propensity score (PS) for the use of TAC was derived, and 471 PS-matched patients who received MTX alone or MTX with other non-biologic disease-modifying antirheumatic drugs (except for TAC), but not with biologics, were selected and served as the control group. Changes in disease activity in the two groups during three consecutive IORRA phases were analyzed by adjusting for confounding factors.

Results The median 28-joint disease activity score (DAS28) decreased from 4.58 to 3.70 in the MTX + TAC group and from 4.12 to 3.61 in the control group. After adjusting for confounding factors, the decrease in the DAS28 score in the MTX + TAC group was significantly larger (by 0.273 points) than that in the control group (P < 0.05).

Conclusion: This study demonstrated the efficacy of add-on therapy with TAC to MTX in patients with RA in daily practice.     

Evaluation of Pneumocystis pneumonia infection risk factors in patients with connective tissue disease

Abstract

We conducted a retrospective, clinical evaluation of connective tissue disease (CTD) patients who were tested for either sputum or bronchoalveolar lavage fluid Pneumocystis polymerase chain reaction (PC-PCR) and analyzed the risk factors that cause Pneumocystis pneumonia (PCP) susceptibility and fatality. PC-PCR was performed on 66 CTD patients who presented with symptoms, data, or radiological findings strongly suggesting respiratory infection. Patients with higher oral corticosteroid doses, use of oral methotrexate (MTX), bilateral lung findings, positive β-d-glucan, and no prophylaxis use were more susceptible to PCP. They had significantly low immunoglobulin G and significantly high β-d-glucan and lactate dehydrogenase. Survivors and nonsurvivors of PCP were also evaluated. Poor prognoses were observed with older age, elevated β-d-glucan, rheumatoid arthritis (RA) patients using MTX, hypoxemia, bilateral lung findings, and mechanical ventilation use. Nonsurvivors had significantly lower lymphocytes, oxygen saturation, and significantly higher β-d-glucan. In RA, poor prognoses were seen with those taking MTX. Disease duration, underlying pulmonary complications, and oral corticosteroid doses did not lead to poor prognoses in RA. Because PCP in CTD leads to abrupt onset of symptoms with poor survival rates, early diagnosis and initiation of treatment are critical, and it is essential for clinicians to recognize risk factors that predispose patients to PCP and its mortality.     

Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents

Objectives: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD.

Methods: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development.

Results: Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p?=?0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3?mg/w, p?=?0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein–Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p?=?0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy.

Conclusions: Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.     

Leading causes of methotrexate and antimalarial drugs discontinuation in Iranian patients with rheumatoid arthritis

BackgroundMethotrexate (MTX) and anti-malarial drugs are widely prescribed for rheumatoid arthritis (RA) as disease-modifying anti-rheumatic drugs (DMARDs). Some patients discontinue treatment because of their adverse effects which could induce disease reactivation.Aim of the workWe aimed to evaluate common causes of DMARD discontinuation such as MTX, chloroquine (CQ) and hydroxychloroquine (HCQ) in patients with rheumatoid arthritis.Patients and methodsWe reviewed the records of RA patients referred to the rheumatologic clinic of Shariati Hospital in 2006 and their records were retrospectively reviewed till 1991. Patients who received MTX (with or without CQ or HCQ consumption) for at least one month were included to determine the frequency and more prevalent causes of drug discontinuation.ResultsAmong 295 RA patients, 28.5% discontinued MTX. Adverse drug effects were found in 27.4% of the patients. However, no serious adverse events such as cirrhosis were reported. Among 271 patients who received antimalarial agents, 41.3% discontinued treatment. 51.3% of drug withdrawals were because of ophthalmological consultation and presence of retinopathy, macular pigmentation, and keratopathy, without any persistent or serious ocular complication such as blindness. Only patients who discontinued treatment due to retinopathy were significantly older than the others.ConclusionWith respect to the relatively low rate of discontinuation due to adverse effects, MTX seems to be a safe drug for long-term use in RA patients. Serial eye examination for those using antimalarial drug will protect them against ocular toxicity which could further lead to higher rates of drug discontinuation.     

Pneumocystis jiroveci pneumonia associated with low-dose methotrexate treatment for rheumatoid arthritis: report of two cases and review of the literature

Low-dose methotrexate (MTX) therapy is widely used for rheumatoid arthritis (RA) because of its favorable efficacy and toxicity profile. Although Pneumocystis jiroveci pneumonia (PCP) is most often seen in severely immunosuppressed patients, PCP complicating low-dose MTX therapy for RA has been reported to sometimes occur. We herein report two cases of patients who developed PCP during treatment with low-dose MTX, and discuss the importance of prophylaxis for this opportunistic infection.     

The three-year efficacy of iguratimod in clinical daily practice in patients with rheumatoid arthritis

Abstract

Objectives: To assess the middle-term outcome of iguratimod (IGU) in rheumatoid arthritis (RA) patients.

Methods: Sixty-nine RA patients (14 males and 55 females, mean age of 64.0 years) receiving IGU-containing therapies were enrolled. We divided these patients into three groups based on the treatment at the baseline: an IGU group, a methotrexate (MTX) plus IGU group, and a biologics plus IGU group. The baseline characteristics and clinical course were evaluated over three years. Predictive factors associated with the achievement of low disease activity (LDA) were statistically analyzed.

Results: The survival rate of IGU therapy at 3 years was 40.6%. The disease activity was significantly decreased in the IGU group and MTX plus IGU group compared with the baseline. Furthermore, 38 patients (55.1%) were in remission or had LDA at 3 years. The patient gender, use of prednisolone (PSL) and DAS28-CRP at baseline were the factors associated with the achievement of remission or LDA at three years.

Conclusion: IGU was effective without MTX or bDMARDs as well as in combination with MTX. A female gender, no use of PSL and a low DAS28-CRP at the initiation of IGU were associated with clinical remission or LDA achievement at three years.     

Asymptomatic carriage of Pneumocystis jiroveci in elderly patients with rheumatoid arthritis in Japan: a possible association between colonization and development of Pneumocystis jiroveci pneumonia during low-dose MTX therapy

Abstract

Low-dose methotrexate (MTX) has been used effectively for rheumatoid arthritis (RA) because of its favorable risk-benefit ratio. One of the recent concerns arising from this therapy is a possible increase in the rate of opportunistic infections, particularly Pneumocystis jiroveci pneumonia (PCP). In this study, we report two cases of PCP occurring during low-dose methotrexate therapy for RA and review 13 additional cases from the literature on Japanese patients with RA. The average age of these patients was 67.7 years, and most were over the age of 60. MTX-associated PCP appears to occur more frequently in elderly individuals in Japan. To identify individuals with a high risk of PCP, we performed a polymerase chain reaction on specimens from induced sputum or bronchoalveolar lavage fluids from 55 patients with RA. At that point in time, they showed no evidence of PCP development. We found six patients (10.9%) having asymptomatic carriage of P. jiroveci. The mean age of the P. jiroveci-positive patients was 74.7 years, which was significantly older than the P. jiroveci-negative patients (mean age 63.6 years). Of the RA patients over the age of 65, 18.8% (6 cases out of 32) were carriers of P. jiroveci. There were no significant differences in RA duration or counts of white blood cells or lymphocytes between the positive and negative groups. Notably, we encountered a case of PCP occurring in an asymptomatic carrier of P. jiroveci during low-dose MTX therapy for RA. This case appeared to be a reactivation of latent infection. By careful follow-up on the carriers of P. jiroveci, we succeeded in promptly diagnosing PCP, and we employed the appropriate therapeutic strategies for this possibly life-threatening complication.     

Tumor necrosis factor therapy and the risk of serious infection and malignancy in patients with early rheumatoid arthritis: A meta‐analysis of randomized controlled trials

Objective

To conduct a meta‐analysis of the rates of serious infection and malignancy in patients with early rheumatoid arthritis (RA) who have started anti–tumor necrosis factor (anti‐TNF) therapy and had not received treatment with disease‐modifying antirheumatic drugs (DMARDs) or methotrexate (MTX).

Methods

A systematic literature search was conducted through the summer of 2009. All studies included were randomized, double‐blind, placebo‐controlled trials involving patients with early RA who were started on anti‐TNF therapy without prior DMARD/MTX use. Six trials met the inclusion criteria for the meta‐analysis, comprising a total of 2,183 patients receiving biologic therapy and 1,236 patients receiving MTX. The data extracted were from published trials.

Results

A pooled odds ratio (OR) (determined using Mantel‐Haenszel methods, with a continuity correction designed for sparse data) was calculated for serious infections (requiring hospitalization) and malignancies, comparing anti‐TNF therapy to MTX control. The pooled OR for serious infections was 1.28 (95% confidence interval [95% CI] 0.82–2.00) and that for malignancies was 1.08 (95% CI 0.50–2.32). There was no significant difference in either the rate of serious infections or the rate of malignancies between the anti‐TNF therapy group and the control group.

Conclusion

Whereas other meta‐analyses have shown an increased risk of serious infection and malignancy in patients receiving anti‐TNF therapy, the results of the present meta‐analysis show that there is not an increased risk when the patients have early disease and have not previously been treated with DMARDs and/or MTX.

     

Evaluation of Pneumocystis pneumonia infection risk factors in patients with connective tissue disease

We conducted a retrospective, clinical evaluation of connective tissue disease (CTD) patients who were tested for either sputum or bronchoalveolar lavage fluid Pneumocystis polymerase chain reaction (PC-PCR) and analyzed the risk factors that cause Pneumocystis pneumonia (PCP) susceptibility and fatality. PC-PCR was performed on 66 CTD patients who presented with symptoms, data, or radiological findings strongly suggesting respiratory infection. Patients with higher oral corticosteroid doses, use of oral methotrexate (MTX), bilateral lung findings, positive β-d-glucan, and no prophylaxis use were more susceptible to PCP. They had significantly low immunoglobulin G and significantly high β-d-glucan and lactate dehydrogenase. Survivors and nonsurvivors of PCP were also evaluated. Poor prognoses were observed with older age, elevated β-d-glucan, rheumatoid arthritis (RA) patients using MTX, hypoxemia, bilateral lung findings, and mechanical ventilation use. Nonsurvivors had significantly lower lymphocytes, oxygen saturation, and significantly higher β-d-glucan. In RA, poor prognoses were seen with those taking MTX. Disease duration, underlying pulmonary complications, and oral corticosteroid doses did not lead to poor prognoses in RA. Because PCP in CTD leads to abrupt onset of symptoms with poor survival rates, early diagnosis and initiation of treatment are critical, and it is essential for clinicians to recognize risk factors that predispose patients to PCP and its mortality.     

Factors associated with methotrexate dosing and therapeutic decisions in veterans with rheumatoid arthritis

The purpose of this study is to explore patient factors associated with differences in methotrexate (MTX) dosing and to compare patient factors and MTX-dosing patterns between those who remained on MTX monotherapy and those who were switched or had additional therapy. A retrospective cohort of 7,017 patients with newly diagnosed rheumatoid arthritis (RA) was identified in the United States Department of Veterans Affairs administrative databases between 1 October 1999 and 30 September 2009. Regression analyses were used to study the association of MTX start and maximum dose attained with various patient characteristics and compare differences between groups who had therapeutic change (having switched to or added another anti-rheumatic agent or having steroids increased by 2.5 mg of prednisone or equivalent) with those remaining on MTX monotherapy. Abnormal serum creatinine (>1.5 mg/dL) was associated lower start and peak MTX doses (p?<?0.01). Older RA patients were less likely to attain peak MTX dose of 15 mg or more (p?<?0.01). Males and patients 75 and older (compared with <45) had lower risk of therapeutic change (hazard ratio, [HR] 0.80, 95 % confidence interval [CI] 0.72–0.90, and HR 0.42, 95% CI 0.42–0.36–0.50, respectively). Patients who attained higher peak MTX dose had lower risk of therapeutic change compared with those dosed at less than 15 mg/week (HR 0.85, 95% CI 0.77–0.92 for 15 to <20 and HR 0.79, 95% CI 0.72–0.86 for 20 or more). Injectable MTX use conferred lower risk of therapeutic change (HR 0.64, 95% CI 0.52–0.78). Two thirds did not attain a maximum MTX dose of 20 mg/week or more before therapeutic change occurred. Older age and renal insufficiency were barriers to the use of higher MTX maximum dosages. Use of injectable MTX and higher maximum MTX dose were independently associated with higher likelihood to remain on MTX monotherapy. Further studies are needed to explore targeted interventions that may optimize MTX dosing to improve success rates of MTX monotherapy.     

Addition of another disease-modifying anti-rheumatic drug to methotrexate reduces the flare rate within 2 years after infliximab discontinuation in patients with rheumatoid arthritis: An open,randomized, controlled trial

Abstract

Objectives. We examined whether the addition of another conventional disease-modifying anti-rheumatic drugs (DMARDs) to methotrexate (MTX) upon infliximab (IFX) discontinuation in well-controlled rheumatoid arthritis (RA) patients could suppress subsequent disease flare.

Methods. RA patients maintaining DAS28-CRP (Disease Activity Score of 28 joints with C-reactive protein) scores < 2.6 for ≥ 6 months with IFX were randomized either to receive addition of bucillamine (BUC) to MTX (BUC + MTX group; n = 24) or not (MTX group; n = 31) upon discontinuing IFX. The primary endpoint was the flare rate within 2 years of IFX discontinuation.

Results. Six patients discontinuing MTX during the study were excluded from analyses. Seventeen patients (63.0%) experienced flares in the MTX group, which was significantly reduced in the BUC + MTX group (31.8%; p = 0.045). Further, the flare rates differed significantly between remission and non-remission by a Boolean definition upon IFX discontinuation in the MTX group (40.0% vs. 91.7%, respectively; p = 0.014), but they were comparable in the BUC + MTX group. BUC treatment was interrupted in seven patients due to rash, proteinuria and incompliance.

Conclusions. DMARDs combination therapy may be a better treatment strategy than MTX monotherapy for maintaining RA control after successful discontinuation of biological agents.     

Prediction of DAS28-ESR remission at 6 months by baseline variables in patients with rheumatoid arthritis treated with etanercept in Japanese population

Abstract

We tried to determine which baseline variables are responsible for remission induction at 6 months in unselected rheumatoid arthritis (RA) patients of Japanese population treated with etanercept. One hundred forty-one patients with RA who were administered etanercept were registered. Thirty-four patients were started on etanercept monotherapy, 60 patients on cotherapy with methotrexate (MTX) (MTX cotherapy), and 47 patients on cotherapy with other non-MTX nonbiologic disease-modifying antirheumatic drugs (DMARDs) (non-MTX cotherapy). None of the patients were treated with both MTX and non-MTX nonbiologic DMARDs at entry. Outcome was set as achievement of disease activity score 28 (DAS28)-ESR remission at 6 months. We examined association of gender, DAS at baseline, MTX cotherapy at baseline, non-MTX cotherapy at baseline, and prednisolone use at baseline with achievement of remission at 6 months by logistic regression analysis. All subjects were classified as having high (N = 109) or moderate disease activity (N = 32) at entry. One hundred twenty out of 141 patients (85.1%) continued treatment with etanercept at 6 months. Continuation rate was statistically higher in MTX cotherapy (93.3%) compared with etanercept monotherapy (73.5%), and tended to be higher than with non-MTX cotherapy (85.1%). Logistic regression analysis identified that MTX cotherapy at entry and moderate disease activity at entry were independent variables for remission induction at 6 months. Accordingly, DAS28-ESR at 6 months was significantly lower with MTX cotherapy as compared with etanercept monotherapy or non-MTX cotherapy. To a lesser extent, DAS28-ESR with non-MTX cotherapy at 6 months was lower than with etanercept monotherapy. In this study of unselected patients, use of MTX and moderate disease activity at entry were associated with higher likelihood of response to etanercept. Non-MTX nonbiologic DMARDs may be an alternative in RA patients administrated etanercept who are intolerant to MTX.     

The rheumatoid arthritis patient in the clinic: comparing more than 1,300 consecutive DMARD courses

BACKGROUND: Therapy of rheumatoid arthritis (RA) is typically characterized by the sequential use of disease-modifying anti-rheumatic drugs (DMARDs). This study aimed to reveal treatment patterns with traditional DMARDs and their changes during the two decades before the recent introduction of new DMARDs. METHODS: A total of 593 RA patients were followed from their first presentation to our clinic throughout the course of their disease; 222 patients received their first DMARD therapy while under our care. More than 2,300 patient years of therapy were analysed for the efficacy [using C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as surrogates] and duration of drug therapy of consecutive DMARDs. RESULTS: Before 1985, 65-90% of initial DMARDs were gold compounds, but their use decreased continuously thereafter. Antimalarial (AM) drugs were important initial DMARDs in new patients at all times, whereas sulphasalazine (SSZ) and methotrexate (MTX) gained increasing significance after 1985 (the first DMARD was MTX in up to 29% of new patients). Penicillamine (DPA), azathioprine (AZP), cyclosporin (CyA) and combination therapies were not usually employed initially, but were reserved for the later course of the disease. Gender, age and rheumatoid factor were not different between patients receiving different DMARDs. The baseline acute-phase response was higher in patients treated with MTX (mean CRP 3.5 mg/dl) than in those treated with SSZ (CRP 2.4 mg/dl; P < 0.05) or AM (CRP 2.1 mg/dl; P < 0.05), suggesting that MTX was used preferentially in patients with high disease activity. On the other hand, once AM or SSZ had been discontinued, MTX was the most common subsequent DMARD (in 31 and 56% respectively). Comparison of first DMARDs with subsequent ones revealed that first DMARDs were more effective: the acute-phase response decreased most prominently during first therapies (CRP reduction was 1.28 mg/dl during first courses and 0.35 mg/dl during fourth or later courses; P < 0.01); and retention rates were significantly longer for first compared with subsequent therapies (median of 24.5 months for first and 18.6 months for fourth or subsequent therapies; P < 0.001). CONCLUSION: MTX was the most commonly employed DMARD therapy for RA and was used increasingly as first therapy in newly diagnosed RA. Patients with high disease activity were given MTX therapy more often than other DMARDs, while those with low activity were more likely to receive SSZ or AM, and MTX on failure of these drugs. First DMARDs in new patients were retained longer than subsequent DMARDs, apparently because they are more effective.     

High-resolution CT and pulmonary function tests in rheumatoid arthritis patients with subclinical interstitial lung disease in Kuwait

BackgroundInterstitial lung disease (ILD) is a frequent extra-articular manifestation of RA and can cause significant morbidity and mortality.Aim of the workTo characterize and define the frequency of radiological and functional abnormalities capable of identifying “subclinical” RA-ILD with particular concern to the effect of methotrexate (MTX) therapy.Patients and methodsSixty patients with RA were recruited with no respiratory manifestations. They were classified into two groups: group 1 included 35 patients receiving MTX and group 2 included 25 patients receiving only nonsteroidal anti-inflammatory drugs. Patients were also classified according to chest high resolution CT (HRCT) as RA-ILD or RA-noILD. Pulmonary function test (PFT) abnormalities were also used to further characterize occult respiratory defects.Results38.3% of RA patients had subclinical ILD (25% in group 1 and 13.3% in group 2), while 61.7% were RA-no ILD. The percentage of patients with RA-ILD was insignificantly more in group 1 than group 2 (42.9% and 32% respectively). HRCT score revealed minimal to mild involvement in both groups. Long-standing RA with mean articular duration >50 months carries a significant risk for ILD. Other variables as age, gender, smoking, disease activity or rheumatoid factor seropositivity were not significant risk factors for development of RA-ILD.ConclusionsLung involvement should always be considered in patients with RA particularly those on MTX therapy even in the absence of chest symptoms. A tight control by PFTs, chest radiography and/or HRCT is necessary. Further studies evaluating the potential effect of MTX on progressive ILD with RA are needed.     

How aggressive should initial therapy for rheumatoid arthritis be? Factors associated with response to 'non-aggressive' DMARD treatment and perspective from a 2-yr open label trial

OBJECTIVE: To determine what baseline factors might be associated with response to an initial mild treatment regimen in patients with early rheumatoid arthritis (RA). METHODS: Open label 2-yr study of 111 consecutive patients with early RA of duration less than 1 yr. None of the patients had previously received disease-modifying anti-rheumatic drugs (DMARDs). All patients were assigned to receive hydroxychloroquine (HCQ) at enrollment, and could also take non-steroidal anti-inflammatory drugs (NSAIDs) and prednisone. At any point during follow-up, patients not fulfilling the American College of Rheumatology (ACR) 50 criteria for improvement and/or who were taking prednisone > 10 mg/day were considered treatment failures and therapy changed to methotrexate (MTX), 7.5-20 mg/week. Clinical, laboratory and immunogenetic factors potentially predictive of treatment assignment at month 24 were evaluated. RESULTS: After 24 months of follow-up, a majority of patients (56/94) were either still on solo DMARD therapy with HCQ (n = 49) or off DMARD therapy with controlled/quiescent disease (n = 4), and 38 patients were taking MTX (including 11 in combination with other DMARDs). At month 24, all but 9 patients met ACR50 criteria for treatment response. Features present at enrollment which were predictors of MTX therapy at month 24 were high pain score, baseline rheumatoid factor titre > 1:40, higher number of swollen joints, and poor patient global assessment. The presence of HLA-C7xx at enrollment was also predictive of need for MTX therapy. CONCLUSIONS: This study suggests that even milder treatment with HCQ is greatly beneficial in patients with early RA. There continue to be very few consistently reliable predictors of treatment needs in patients with this disease.     

Baseline comorbidities in patients with rheumatoid arthritis who have been prescribed biological therapy: A case control study

AimTo determine whether rheumatoid arthritis (RA) patients who have been prescribed biological agents exhibit a different comorbidity burden than RA patients who take disease-modifying antirheumatic drugs (DMARDs) alone, and to understand the association between comorbidity and other variables, as well as the association between comorbidity and multimorbidity.MethodsThis observational case–control study included 114 RA patients treated with biological agents and a control group comprising 163 sex- and age-matched RA patients treated with DMARDs only. Current and previous data regarding the patients’ disease activity, comorbidities, and treatments were collected. The data were analysed using bivariate and multivariate regression models.ResultsThe patients who were prescribed biological agents exhibited poorer disease control, received more DMARDs and steroids, and underwent more total joint arthroplasties compared with the patients in the control group. However, the risk factors for cardiovascular disease and the comorbidity frequency were similar between cases and controls. The most prevalent comorbidities were hypertension, obesity, and respiratory, thyroid, and upper gastrointestinal disorders. The incidence of cardiovascular disease was low, and only 29% of the patients exhibited multimorbidities. A bivariate association of age, late diagnosis, joint replacements and a high score on the health assessment questionnaire score (HAQ) with comorbidity was observed. There were also correlations between the Charlson index and age, joint reconstructive surgery, disease activity (DAS28), and HAQ score. However, when binary logarithmic regression models were applied, only patient age remained significantly associated with comorbidity and multimorbidity [hazard ratio, 1.08; 95% confidence interval, 1.05–1.12; p < 0.0005].ConclusionRA patients taking biological drugs have a comorbidity burden equivalent to those treated with DMARDs alone. Age is the main predictive factor of comorbidity in these patients.