Non-steroidal Anti-inflammatory Drugs Monotherapy Research Articles

Do disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs increase the burden on ankylosing spondylitis patients with mild-moderate COVID-19? evidence from a retrospective cohort study

Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19.Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes.Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2–46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84–1.40 or 1.09, 0.92–1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01–1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26–1.64; 0.95, 0.36–2.54; and 1.01, 0.53–1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82–1.66; 1.18, 0.78–1.77; and 1.22, 0.92–1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31–2.81; 0.97, 0.25–3.74 and 1.05, 0.44–2.49, respectively) compared to those not using medication.Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.

Cause analysis of conversion to biologics in spondyloarthritis patients with poor response to conventional treatment.

We sought to investigate the reasons why spondyloarthritis (SpA) patients failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic disease-modifying antirheumatic drugs (cDMARDs) and the influences of different initial cDMARDs on the likelihood of a switch to biologics. SpA patients were divided into a conventional drug maintenance group and a biologics conversion group to determine the causes of conversion to biologics. Then, we divided all patients into three groups according to different initial cDMARDs, NSAID monotherapy, NSAID + (sulfasalazine or thalidomide) double combination, and NSAID + sulfasalazine + thalidomide triple combination therapy groups, to clarify the influence of initial treatment on later conversion to biologics. This study includes 202 patients, including 97 patients in the conventional drug maintenance group and 105 patients in the biologics conversion group. The mean age of the conventional drug maintenance group was higher than that of the biologics conversion group (40.8 ± 14.3 vs. 33.8 ± 12.3 years, P < 0.05). Uveitis (OR 5.356, P < 0.05) is positively correlated with conversion to biological therapy, while age (OR 0.940, P < 0.05) is negatively correlated. The proportion of NSAID monotherapy, double combination, and triple combination groups converted to biological agents was 80%, 51.1%, and 23.2%, respectively (P < 0.05). Age and uveitis are related to conversion to biologics therapy. The early combination of sulfasalazine and thalidomide with NSAIDs may lower the probability of conversion to biologics therapy in the later stage and offer a new option for patients with limited use of biologics in SpA patients. Key Points • Patients' move to biologics may be caused mostly by inadequate disease control by conventional oral medications. • Regardless of axial vs. peripheral joint involvement, combination drug therapy was superior to single drug therapy in controlling SpA and decreasing the probability of conversion to a biological agent. • For SpA patients who are not candidates for biologics due to contraindications or other reasons, early combination application of NSAIDs, sulfasalazine, and thalidomide may be a new choice.

Comparison of Colchicine Monotherapy Versus Nonsteroidal Anti-Inflammatory Drugs Monotherapy or Combination Therapy for the Prevention of Recurrent Pericarditis in Patients With Heart Failure With Reduced Ejection Fraction and/or Coronary Artery Disease.

Objective: Guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin for 2-4 weeks with colchicine for 3 months for the treatment of acute pericarditis. In patients with HFrEF and/or CAD, the adverse effect profile of NSAIDs pose concern. While previous studies evaluated colchicine as adjunctive therapy, colchicine monotherapy has never been assessed. This study aims to compare the efficacy of colchicine monotherapy to NSAID monotherapy or combination therapy for the prevention of recurrent pericarditis in patients with HFrEF and/or CAD. Methods: This was a single health-system, retrospective, observational cohort study. Patients were 18 years or older, had a diagnosis of acute pericarditis and HFrEF and/or CAD, and were discharged on colchicine and/or NSAID therapy. Patients were excluded if they had an episode of pericarditis within the previous 12 months. The primary outcome was the incidence of pericarditis recurrence or documentation of incessant symptoms within 12 months of the index hospitalization. Results: Of the 77 patients included, 43 (55.8%) were treated with colchicine monotherapy, 7 (9.1%) were treated with NSAID monotherapy, and 27 (35.1%) were treated with combination therapy. Pericarditis recurrence or documentation of incessant symptoms occurred in 16.3% of patients treated with colchicine monotherapy, 28.6% of those treated with NSAID monotherapy, and 18.5% of those treated with combination therapy (P = .740). Conclusion: In this study, no difference in the primary outcome was observed between groups. However, a prospective, randomized trial is needed to further elucidate the efficacy of colchicine monotherapy for the treatment of acute pericarditis in patients with HFrEF and/or CAD.

Prednisolone and Ketorolac vs Ketorolac Monotherapy or Sub-Tenon Prophylaxis for Macular Thickening in Cataract Surgery

The choice of anti-inflammatory prophylaxis parallel to cataract surgery is important for patient safety and successful outcome of surgery, but which regimen to choose is contested. To determine whether a combination of prednisolone and nonsteroidal anti-inflammatory drug (NSAID) eye drops was superior in preventing increased central macular thickness (central subfield thickness [CST]) after uncomplicated cataract surgery compared with NSAID monotherapy and sub-Tenon capsule depot (dropless surgery), and to test whether preoperative initiation of eye drop treatment was superior to initiation on the day of surgery. This investigator-driven, single-center, randomized clinical trial with masked statistical analyses enrolled patients at the Department of Ophthalmology, Rigshospitalet Glostrup, Glostrup, Denmark, from February 1, 2018, to August 15, 2019. Follow-up was completed December 18, 2019. Participants included low-risk patients undergoing phacoemulsification for age-related cataract by an experienced surgeon (1 eye per participant). Data were analyzed from February 17 to June 15, 2020. Participants scheduled for cataract removal were randomized to 1 of 5 anti-inflammatory prophylactic regimens: eye drops with a combination of prednisolone, 1%, and ketorolac tromethamine, 0.5%, with or without preoperative initiation (preoperative prednisolone plus NSAID [control] and postoperative prednisolone plus NSAID groups), ketorolac monotherapy with or without preoperative initiation (preoperative and postoperative NSAID groups), or sub-Tenon depot of dexamethasone phosphate (sub-Tenon group). Eye drops were administered 3 times per day until 3 weeks postoperatively. CST 3 months postoperatively. A total of 470 participants (mean [SD] age, 72.2 [7.0] years; 290 women [61.7%]) with 94 participants in each group were included in the analysis. Three months after surgery, the mean CST was 250.7 (95% CI, 247.6-253.7) μm in the preoperative prednisolone plus NSAID group, 250.7 (95% CI, 247.8-253.7) μm in the postoperative prednisolone plus NSAID group, 251.3 (95% CI, 248.2-254.4) μm in the preoperative NSAID group, 249.2 (95% CI, 246.2-252.3) μm in the postoperative NSAID group, and 255.2 (95% CI, 252.0-258.3) μm in the sub-Tenon group. There were no significant differences in CST or visual acuity compared with control and no differences between preoperative and postoperative groups, but 47 of 83 participants (56.6%) in the sub-Tenon group needed additional anti-inflammatory treatment. No differences in CST or visual acuity were detected between the combination of prednisolone and NSAID eye drops vs NSAID monotherapy or sub-Tenon dexamethasone depot, although more than one-half of patients in the sub-Tenon arm received additional anti-inflammatory treatment. Initiating prophylaxis 3 days preoperatively was not superior to initiation on the day of surgery. Monotherapy with NSAIDs may be preferred in uncomplicated cataract surgery. ClinicalTrials.gov Identifier: NCT03383328.

B vitamins and nonsteroidal anti-inflammatory drugs: the efficacy of the combination for nonspecific back pain

Back pain significantly affects quality of life in patients. Therapy for acute and chronic nonspecific back pain (NBS) includes non-drug and drug treatments. The non-drug treatment includes educational conversations with a patient, recommendations to maintain an active lifestyle, therapeutic exercises, behavioral and cognitive-behavioral therapy, and mindfulness. Manual therapy and injections of anesthetics into the area of tender joints may be prescribed. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for drug treatment of acute and chronic NBS. Antidepressants may be prescribed for chronic pain and depression symptoms. B vitamins (thiamine, pyridoxine, and cyanocobalamin) can be considered as adjuvant analgesics in NBS. The results of animal experimental studies have shown that B vitamins at high doses have analgesic and anti-inflammatory effects. Clinical studies, a systematic review, and a meta-analysis published in 2020 demonstrated the safety and advantages of combination therapy with NSAIDs and B vitamins over NSAID monotherapy in the treatment of acute NBS and exacerbations of chronic NBS. The addition of B vitamins to NSAIDs can reduce the duration of treatment by 2 times. By reducing the duration of pharmacotherapy, the risk of adverse reactions to NSAIDs decreases and the patient returns to daily activities more quickly. It is advisable to conduct further, larger studies of combined pharmacotherapy for NBS.

Effect of anti-inflammatory regimen on early postoperative inflammation after cataract surgery.

To investigate whether a combination of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids were superior in controlling early postoperative inflammation after cataract surgery compared with topical NSAIDs alone and with dropless surgery where a sub-Tenon depot of steroid was placed during surgery. Department of Ophthalmology, Rigshospitalet-Glostrup, Denmark. Prospective randomized controlled trial with masked statistical analyses. Patients undergoing phacoemulsification for age-related cataract were randomized to 1 of 5 regimens: ketorolac and prednisolone eyedrops combined (Pred+NSAID-Pre [control group] and Pred+NSAID-Post group) vs ketorolac monotherapy (NSAID-Pre and NSAID-Post groups) vs sub-Tenon depot of dexamethasone (dropless group). Drops were used until 3 weeks postoperatively, starting 3 days preoperatively in the Pre groups and on the day of surgery in the Post groups. Aqueous flare was measured at baseline and 3 days postoperatively. Four hundred fifty-six participants, with a mean age of 72.1 (SD 7.0) years and 283 (62%) women, were included. Flare increased significantly more in the dropless group compared with the control group (Pred+NSAID-Pre), but none of the other groups differed significantly from the control group. Intraocular pressure decreased in all groups but significantly less in groups receiving prednisolone eyedrops (Pred+NSAID-Pre and Pred+NSAID-Post groups) compared with NSAID monotherapy and dropless groups. No differences in postoperative visual acuity were found compared with the control group. No differences were found between groups randomized to NSAID monotherapy or combination of NSAID and steroid in controlling early inflammation after cataract surgery, but sub-Tenon depot of dexamethasone was less efficient. Initiating prophylactic eyedrops prior to surgery did not influence early postoperative anterior chamber inflammation.

Influence of therapeutic drugs on different manifestations of renal involvement in 907 Chinese patients with ankylosing spondylitis .

There is no systematic or large-scale study in the published literature in which the relationship between drug therapies and renal involvement in ankylosing spondylitis (AS) has been rigorously evaluated. In addition, the sensitivity of the kidneys to drugs varies significantly between races and regional populations. Therefore, the aim of the present study was to investigate the impact of drugs on renal involvement in Chinese AS patients. The clinical characteristics and biochemical data of 907 AS patients were collected and analyzed, and the differences between patients who had received drugs and those who had not were analyzed using intergroup comparisons to screen out confounding factors. Multivariate logistic regression analysis that corrected for the confounding factors explored the impact of the AS therapeutic drugs on the clinical manifestations of renal involvement. Renal involvement in Chinese AS patients increased significantly following non-steroidal anti-inflammatory drug (NSAID) or conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) monotherapy, and combination therapy with NSAIDs, csDMARDs, and TNF-α inhibitor. For AS patients, NSAID monotherapy increased the probability of hematuria 2.4-fold and the probability of mixed manifestations of renal involvement 3.0-fold. csDMARD monotherapy increased the probability of proteinuria 2.4-fold; combination therapy with NSAIDs, csDMARDs, and TNF-α inhibitor increased the probability of hematuria 4.1-fold. In addition, the study found that TNF-α inhibitor monotherapy and combination therapy with NSAIDs or csDMARDs caused no apparent impact on renal involvement in AS patients. NSAID or csDMARD monotherapy may significantly increase renal involvement in Chinese AS patients. Combination therapy with TNF-α inhibitor with NSAIDs and csDMARDs should be used prudently.

Add-On Effects of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs in Ankylosing Spondylitis: Data from a Real-World Registered Study in China.

BackgroundThe aim of this study was to investigate the effects of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on patients with ankylosing spondylitis (AS) using real-world data, and to analyze patients’ choices of csDMARDs and reasons for discontinuation.Material/MethodsThis observational study included 320 patients satisfying the modified New York criteria for AS. Patients were grouped according to medication: Group 1: 122 patients receiving non-steroidal anti-inflammatory drug (NSAID) monotherapy; Group 2: 198 patients receiving csDMARDs and NSAIDs. Patients were followed for 18 months at 6-month intervals. The change in AS Disease Activity Score and C-reactive protein (ASDAS-CRP) at each visit was the primary outcome. Secondary outcomes were based on validated disease activity questionnaires, clinical assessment, and acute-phase biomarkers (CRP and erythrocyte sedimentation rate [ESR]). Inter-group relationships were assessed across the 18-month follow-up period using generalized additive mixed models.ResultsSulfasalazine and thalidomide were the most commonly used csDMARDs, with cumulative use times of 8.9±4.1 months and 9.1±4.7 months, respectively. In Group 2, 56 patients discontinued or switched csDMARDs during the follow-up period, with lack of efficacy being the primary reason. The ASDAS-CRP was found to decrease significantly in both groups; however, improvements in many parameters (including ASDAS-CRP, disease activity questionnaires and ESR) were greater in Group 2.ConclusionsUse of csDMARDs can improve disease activity in terms of ASDAS-CRP. The addition of csDMARDs may provide increased benefits compared with NSAID monotherapy, particularly in the reduction of AS disease activity, in the Chinese population.

Factors influencing the efficacy of nonsteroidal anti-inflammatory drugs for acute low back pain. The results of the multicenter observational «CARAMBOL» (Clinical Analysis of Results of Analgesia by Meloxicam and its Safety in Acute Lumbodynia) study

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a main tool to treat acute nonspecific low back pain (NLBP). However, no factors that influence the efficacy of these drugs have been identified to the present day.Objective: to evaluate the therapeutic effect of and tolerance to NSAIDs (meloxicam) in treating acute NLBS and to identify the factors influencing the efficacy of this drug.Patients and methods. A study group consisted of 2078 patients (mean age 46.3±13.4 years; women 56.6%) with acute NLBS who had been treated in real clinical practice. The level of pain was estimated using a 0–10 point numerical rating scale (NRS). Initially, the pain level averaged 6.69±1.65 scores; 57.0% of patients were noted to have severe pain (≥7 NRS scores). Pain at rest persisted in 32.0% of patients; that at night was in 19.0%; sensation of stiffness in 60.7%, irradiation to the leg in 28.2%, and lumbar ischialgia in 9.6%. 70.2% of patients had been previously treated with NSAIDs for NLBS, while only 28.0% rated their efficacy as good. All the patients were prescribed meloxicam at a dose of 15 mg/day for a period of up to 2 weeks. 86.1% of the patients received meloxicam intramuscular for 2 days, then orally; 13.9% took the drug only orally. 52.3% of the patients also used muscle relaxants; 17.4% received oral or intramuscular B vitamins. The study estimated the rate of complete pain relief when NSAIDs were used for up to 2 weeks.Results and discussion. Complete pain relief was achieved in 75.2% of patients. 83.7% of patients rated the effect of treatment as good or excellent. Undesired drug reactions were recorded in 4.6% of patients. Female gender had no effect on treatment outcome (odds ratio (OR)=0.967; 95% confidence interval (CI), 0.795–1.177; p=0.763). Age over 65 years, the first NLBS episode, and a good NSAID effect in a history were associated with the best treatment result: OR=2.053 (95% CI, 1.5920–2.642), p&lt;0.001; 1.415 (1.09–1.836), p=0.009; and 1.937 (1.513–2.481), p&lt;0.001, respectively. Severe pain (≥7 NRS scores), persistent pain at rest and at night, and especially lumbar ischialgia indicated the worst result: OR=0.481 (95% CI, 0.393–0.588), p&lt;0.001; 0.559 (0.441–0.709), p&lt;0.001; 0.511 (0.413–0.631), p&lt;0.001; and 0.346 (0.256–0.466), p&lt;0.001, respectively. NSAIDs in combination with muscle relaxants and B vitamins versus NSAID monotherapy did not increase the likelihood of pain relief: OR=0.827 (95% CI, 0.594–0.889), p=0.02 and 0.917 (0.804–1.1201), p=0.452, respectively.Conclusion. Meloxicam at a dose of 15 mg/day is an effective and safe drug to treat acute NLBS. Patient gender has no effect on treatment outcome. Age over 65 years, the first NLBS episode, and a good response to NSAIDs in a history are associated with the best treatment results; and severe pain, persistent pain at rest and at night, irradiation to the leg, and lumbar ischialgia are related to the worst result. NSAIDs in combination with muscle relaxants and B vitamins did not improve treatment outcomes.

Is Pregabalin Effective Against Acute Lumbar Radicular Pain ?

Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for acute lumbar radicular pain accompanying lumbar disc herniation (LDH), but their effects are minimal. The purpose of this study was to evaluate the efficacy and safety of pregabalin (PGB) as an alternative therapy for this condition. Methods Patients with acute lumbar radicular pain accompanying LDH were randomly administered either NSAIDs plus PGB (30 patients) or NSAIDs alone (30 patients) for up to 4 weeks. The primary outcome was leg pain at 2 and 4 weeks. Secondary outcomes were reduction in sleep disturbances and patient global impressions of change (PGIC) at 2 and 4 weeks. Results Four patients in the NSAIDs plus PGB group were deemed ineligible and excluded from the study. Fewer sleep disturbances were reported by patients administered NSAIDs plus PGB compared with the NSAID monotherapy group at both 2 and 4 weeks. Additionally, the NSAIDs plus PGB group showed greater improvement in pain than the NSAID monotherapy group at 4 weeks, although this difference was not significant. PGIC was also significantly better in the NSAIDs plus PGB group than in the NSAID monotherapy group at 4 weeks. The incidence of adverse events was significantly greater in the NSAIDs plus PGB group than in the NSAID monotherapy group. Conclusions The combination of NSAIDs plus PGB is more effective against sleep disturbance than NSAIDs alone in patients with acute LDH, although the control of sciatic pain is minimal. Patients reported satisfactory recoveries could also be obtained, and thus, this combination therapy could be a good option for the conservative treatment of acute lumbar radicular pain, including LDH.

Patient characteristics associated with response to NSAID monotherapy in children with systemic juvenile idiopathic arthritis

BackgroundSystemic juvenile idiopathic arthritis (sJIA) is an auto-inflammatory disease characterized by fever, arthritis, and ≥1 of rash, generalized lymphadenopathy, hepato/splenomegaly, and serositis. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the initial treatments of sJIA, but there is currently no evidence indicating which children should undergo a trial of NSAID monotherapy and which should not. Our objective is to identify presentation characteristics which are associated with response and lack of response to a trial of NSAID monotherapy.MethodsThis is a retrospective single-center cohort study of children diagnosed with sJIA from 2000 to 2014. Patient demographics and disease characteristics were investigated to identify predictors of response to NSAID monotherapy.ResultsEighty-seven children were newly diagnosed with sJIA 2000-2014. Thirteen of the 51 children who received NSAID monotherapy achieved clinically inactive disease (CID) without other medications. Age at presentation (≤8 years old), initial joint count (≤5), and C-reactive protein (CRP) (≤13 mg/dL) at diagnosis were associated with achievement of CID on NSAIDs alone. Physicians were less likely to trial NSAID monotherapy if the patient had either serositis or macrophage activation syndrome (MAS) at diagnosis. Ultimate achievement of CID and time to CID were not significantly affected by whether the patient received a trial of NSAID monotherapy.ConclusionsWhile a subset of children with sJIA can achieve CID with NSAID monotherapy, we recommend against a trial in patients who are >8 years old, with >5 joints involved, or with CRP > 13 mg/dL. Patients who undergo a trial of NSAID monotherapy should follow up within 2-4 weeks to evaluate for possible need for drug escalation. Clinical trials are necessary to confirm these findings.

COURSE OF UVEITIS IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Relapsing uveitis is a serious problem for patients with ankylosing spondylitis (AS). Tumor necrosis factor- α inhibitors significantly reduce the frequency of uveitis attacks in AS patients, but they are not always available. In this connection, it is appropriate to evaluate the effect of traditional disease-modifying antirheumatic drugs on the course of uveitis in AS. Objective: to compare the frequency of uveitis attacks in AS during combined therapy using sulfasalazine (SULF) and nonsteroidal anti-inflammatory drugs (NSAIDs) versus monotherapy with NSAIDs. Subjects and methods. A total of 111 patients with significant AS who had at least one uveitis attack during the disease were examined. 49 subjects received combined therapy including SULF 2 grams daily and NSAIDs for at least 1 year. Six of the 49 patients were noted to have frequently relapsing uveitis (above 3 episodes yearly); 43 had no more than 3 ones per year. The remaining 62 patients took NSAIDs only throughout the follow-up period. Nine of them had an average of 3 uveitis attacks per year; 53 had no more than 3 ones per year. Out of the 49 patients receiving combined therapy with NSAIDs and SULF, 23 took NSAIDs only at least 1 year before SULF use; 10 of them were observed to have frequent relapses in that period and 13 had three or fewer episodes. Results and discussion. The entire group showed an average of 2.06±2.04 uveitis attacks per year during monotherapy with NSAIDs and 1.41±1.83 attacks yearly during combined therapy with NSAIDs and SULF (p = 0.08). Among the patients with less than 3 uveitis attacks per year, the mean number of episodes was significantly fewer during combined therapy than during NSAID monotherapy: 0.99±0.87 and 1.37±0.91, respectively (p = 0.04). Among those with frequently relapsing uveitis (more than 3 attacks per year), the mean number of episodes yearly was not significantly different during NSAID monotherapy and combined therapy: 5.7±2.5 and 5.5±2.7, respectively (p = 0.9). In a subgroup of patients receiving sequentially NSAID monotherapy and combined therapy with NSADs and SULF, 13 patients with three or fewer baseline attacks per year displayed a significant reduction in the frequency of episodes from 1.92±0.96 to 0.4±0.44 (p = 0.00003). During combined therapy versus monotherapy, 10 patients with frequently relapsing uveitis (over 3 episodes yearly) exhibited an insignificant reduction in the number of relapses from 5.9±3.02 to 5.33±1.1 (p = 0.6). Conclusion. Combined therapy with SULF and NSAIDs does not substantially affect the frequency of uveitis episodes in AS patients with frequently relapsing uveitis (above 3 attacks per year), but significantly reduces the number of episodes among patients with its mild course (less than 3 attacks yearly).

EFFICIENCY OF ANTI-INFLAMMATORY THERAPY IN PATIENTS WITH ANKYLOSING SPONDYLITIS ACCORDING TO THE RESULTS OF A PROSPECTIVE FOLLOW-UP STUDY

In accordance with the Ankylosing Spondylitis Assessments (ASAS) International Working Group guidelines, tumor necrosis factor-α inhibitors are recommended in patients with ankylosing spondylitis (AS) refractory to at least two nonsteroidal anti-inflammatory drugs (NSAIDs) and in those with the peripheral form of the disease. Previous investigations suggest that when long used, infliximab (INF) shows a steady-state efficacy in the vast majority of patients with active AS. Works evaluating the efficiency of combined therapy using NSAIDs and INF are scarce. Objective: to evaluate the efficiency of therapy with NSAIDs and INF in patients with AS from the results of a prospective study. Subjects and methods. A total of 72 men with a valid diagnosis of AS were followed up. All the patients were allocated to two groups according to the option of basic therapy: 1) 29 patients received combined therapy with INF and NSAIDs; 2) 43 had NSAID monotherapy. Clinical, laboratory, and instrumental examinations were performed every 12 months. Results and discussion. At 12 months of INF therapy, there were significant reductions in the values of BASDAI, BASFI, back pain, fatigue, and patient-rated global activity assessment. High BASDAI values remained in only 10 patients. At 24-month follow-up, the above measures did not significantly change as compared to the results obtained at 12 months and remained stable at 36 months. At 12 months of NSAID therapy, there were significant reductions in the values of BASDAI, back pain, fatigue, and patient-rated global activity assessment (p < 0.05). The reduction in BASFI values was insignificant. At 24 months of treatment all the measures versus those obtained after 12 months did not significantly change, except pain in the examined region of the spine, which became significantly severer than that at the 12-month follow-up. These results were also preserved at 36 months. There were more patients achieving 20% and 40% improvements and remission according to the ASAS criteria, and those with a 50% BASDAI improvement after 36 months of INF + NSAID therapy versus NSAID monotherapy (p < 0.05). Conclusion. The highest clinical effect of INF + NSAID therapy was observed within the first year and the measures in question remained stable at the 36-month follow-up after both treatments.

Aggressive Therapy Reduces Disease Activity without Skeletal Damage Progression in Chronic Nonbacterial Osteomyelitis.

To retrospectively assess changes in disease activity and skeletal damage in children with chronic nonbacterial osteomyelitis (CNO) after infliximab and methotrexate, with or without zoledronic acid or nonsteroidal antiinflammatory drug (NSAID) monotherapy, using a standardized magnetic resonance imaging (MRI) approach. Treatment-related changes in clinical and MRI measures from aggressive therapy and NSAID monotherapy groups (n = 9 per group) were evaluated using nonparametric methods. Pain, physical function, physician global assessment, inflammatory markers, nonvertebral inflammatory lesion number, and maximum bone edema score all improved significantly with aggressive therapy (p < 0.03), whereas only the maximum soft tissue inflammation severity decreased (p = 0.02) with NSAID monotherapy. Vertebral deformities and physeal damage did not worsen in the aggressive therapy group but 1 in the NSAID group had worsening of growth plate damage. An aggressive treatment regimen in CNO improved clinical and imaging measures of disease activity without progression of skeletal damage.

One-year follow-up for the therapeutic efficacy of pregabalin in patients with leg symptoms caused by lumbar spinal stenosis

Background Pregabalin is a well-accepted treatment option for patients with neuropathic pain. However, the therapeutic efficacy of pregabalin for reducing the incidence of spinal surgery to treat leg symptoms in patients with lumbar spinal stenosis remains unknown. The purpose of this study was to analyze the therapeutic efficacy of pregabalin for reducing the incidence of spinal surgery for leg symptoms in patients with lumbar spinal stenosis during the first year of treatment.Methods Consecutive patients diagnosed with lumbar spinal stenosis at our hospital from January to June 2009 were treated with nonsteroidal anti-inflammatory drug monotherapy and formed the control group (n = 47; 22 males, 25 females). Patients diagnosed with lumbar spinal stenosis at our hospital between August 2010 and October 2011 were treated with a nonsteroidal anti-inflammatory drug and pregabalin combination therapy and formed the pregabalin group (n = 49; 27 males, 22 females). The proportions of patients who underwent spinal surgery during the first year of treatment were assessed and compared between the two groups using the Mann-Whitney U test. In addition, the periods in which patients decided to undergo spinal surgery were compared using the Kaplan-Meier method.Results Six patients (12.2 %) in the pregabalin group and 22 patients (46.8 %) in the control group underwent spinal surgery during the first year of treatment (P = 0.0035). The period in which patients decided to undergo spinal surgery was significantly delayed in the pregabalin group compared with the control group in those for whom spinal surgery was necessary (P = 0.0128).Conclusions Nonsteroidal anti-inflammatory drug and pregabalin combination therapy may result in a lower incidence of spinal surgery during the first year of treatment or a delayed period before undergoing spinal surgery if necessary compared with nonsteroidal anti-inflammatory drug monotherapy in patients with leg symptoms caused by lumbar spinal stenosis.

Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain

To evaluate whether subjects with knee or hip osteoarthritis (OA) pain on non-steroidal anti-inflammatory drugs (NSAIDs) received greater benefit when tanezumab monotherapy replaced or was coadministered with NSAIDs. Subjects (N=2700) received intravenous tanezumab (5 or 10 mg) or placebo every 8 weeks with or without oral naproxen 500 mg twice daily or celecoxib 100 mg twice daily. Efficacy was assessed as change from baseline to week 16 in three co-primary endpoints: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function and Patient's Global Assessment (PGA) of OA. Safety assessments included adverse events, physical and neurological examinations, laboratory tests and vital signs. Although all tanezumab treatments provided significant improvements in WOMAC Pain and Physical Function over either NSAID alone, only tanezumab+NSAIDs were significant versus NSAIDs with PGA and met the prespecified definition of superiority. Combination treatment did not substantially improve pain or function over tanezumab monotherapy. Adverse event frequency was higher with tanezumab than with NSAIDs and highest with combination therapy. Higher incidence of all-cause total joint replacements occurred with tanezumab+NSAID versus tanezumab monotherapy or NSAIDs. Rapidly progressive OA incidence was significantly greater versus NSAID in all tanezumab groups except tanezumab 5 mg monotherapy. Subjects receiving partial symptomatic relief of OA pain with NSAIDs may receive greater benefit with tanezumab monotherapy. While only coadministration of tanezumab with NSAIDs met the definition of superiority, combination treatment did not provide important benefits over tanezumab monotherapy; small differences in efficacy were negated by treatment-limiting or irreversible safety outcomes. NCT00809354.

Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1

ObjectivesTo assess whether combination therapy with infliximab (IFX) plus nonsteroidal anti-inflammatory drugs (NSAIDs) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society (ASAS) partial remission in patients...

Efficacy of non-steroidal anti-inflammatory drug monotherapy in children with systemic juvenile idiopathic arthritis

Purpose Treatment of systemic juvenile idiopathic arthritis (sJIA) is one of the most challenging tasks faced by pediatric rheumatologists. Traditionally, many pediatric rheumatologists have used a “pyramid” approach, starting with non-steroidal anti-inflammatory drug (NSAID) monotherapy prior to the initiation of disease modifying anti-rheumatic drugs (DMARDs) or biologic agents. Despite the widespread use of NSAID monotherapy, the likelihood of response to this regimen has not been well characterized. In addition, some clinicians have recently begun to advocate for the use of biologic agents as first-line therapy for all patients with sJIA, despite the risks of patient discomfort, infection, and malignancy that may be associated with their use. The goals of this study are (1) to determine the frequency of clinical response to NSAID monotherapy in sJIA, and (2) to identify factors that predict that response.

Su1766 Gastroprotective Strategies in Chronic NSAID Users: A Cost-Effectiveness Analysis Comparing Single Tablet Formulations With Individual Components

Background: Non-steroidal anti-inflammatory drugs (NSAID) are associated with gastrointestinal (GI) side effects. Co-therapy with gastroprotective agents (GPA) is therefore recommended in patients at high risk for GI complications. However, compliance with GPAs is low. Single tablet formulations combining GPA with NSAID may enhance compliance and reduce complications. Aim: To evaluate the cost-effectiveness of competing GPA strategies, including combination formulations, in the prevention of GI complications in chronic arthritis patients. Methods: We performed a cost-utility analysis to compare eight gastroprotective strategies including variations of NSAID, cyclooxygenase-2 inhibitors, proton pump inhibitor (PPI), histamine-2 receptor antagonists, misoprostol, and combination tablets. The time horizon was 5 years for a hypothetical 60-year old patient with chronic arthritis requiring long term NSAID-therapy. We derived estimates for outcomes and costs from the medical literature. The primary outcome was incremental cost per quality adjusted life year gained (ICER). Sensitivity analyses were performed to assess the effect of gastrointestinal complications, compliance rates, and drug costs on the outcomes. Results: For the average risk patient, NSAID+PPI co-therapy was a cost-saving and more effective strategy compared to NSAID monotherapy. With an ICER of €35,075 the NSAID/PPI single tablet formulation could only become “viable” (i.e. ICER < €20,000 per QALY gained) when the price decreased from €0,78 to €0,56 per tablet, or when PPI compliance fell below 51% in the NSAID+PPI strategy. All other strategies were more costly and less effective. The model was highly sensitive to the risk of GI complications, costs of PPI and NSAID/PPI single tablet formulation, and compliance. In patients with a 3-fold higher risk of GI complications, both NSAID+PPI co-therapy and the single tablet formulation were cost-effective. With the latter yielding an ICER of €9917. When the costs of PPIs exceeded €0.42/day or compliance to PPIs fell below 33%, the single tablet formulation became a dominant strategy (i.e. more effective and less costly than NSAID+PPI co-therapy). Conclusions: NSAID+PPI co-therapy is a cost-effective and cost-saving strategy in chronic arthritis patients at average risk for GI complications due to NSAID use. The NSAID/PPI single tablet formulation was only cost-effective in highrisk patients. Compliance to PPI was found to be an important and influential factor determining cost-effectiveness for both average and high risk patients.