Patients with cancer often experience comorbidities that may affect their prognosis and outcome. The objective of this study was to determine the effect of comorbidities on the survival of patients ...with myelodysplastic syndrome (MDS).
We conducted a retrospective cohort study of 600 consecutive patients with MDS who presented to MD Anderson Cancer Center from January 2002 to December 2004. The Adult Comorbidity Evaluation-27 (ACE-27) scale was used to assess comorbidities. Data on demographics, International Prognostic Scoring System (IPSS), treatment, and outcome (leukemic transformation and survival) were collected. Kaplan-Meier methods and Cox regression were used to assess survival. A prognostic model incorporating baseline comorbidities with age and IPSS was developed to predict survival.
Overall median survival was 18.6 months. According to the ACE-27 categories, median survival was 31.8, 16.8, 15.2, and 9.7 months for those with none, mild, moderate, and severe comorbidities, respectively (P < .001). Adjusted hazard ratios were 1.3, 1.6, and 2.3 for mild, moderate, and severe comorbidities, respectively, compared with no comorbidities (P < .001). A final prognostic model including age, IPSS, and comorbidity score predicted median survival of 43.0, 23.0, and 9.0 months for lower-, intermediate-, and high-risk groups, respectively (P < .001).
Comorbidities have a significant impact on the survival of patients with MDS. Patients with severe comorbidity had a 50% decrease in survival, independent of age and IPSS risk group. A comprehensive assessment of the severity of comorbidities helps predict survival in patients with MDS.
To identify potential psychosocial and educational barriers to clinical success following knee replacement.
The authors evaluated 241 patients undergoing total knee replacement, preoperatively and 6 ...months after surgery. Outcomes included the Western Ontario McMaster (WOMAC) scale and the Knee Society rating system (KSRS). Independent variables included: the medical outcome study-social support scale; depression, anxiety and stress scale; brief COPE inventory; health locus of control; arthritis self-efficacy scale and the life orientation test-revised. Multiple regression models evaluated associations of baseline demographic and psychosocial variables with outcomes at 6 months, controlling for body mass index, comorbidities and baseline outcome scores.
Patients' mean age was 65 ± 9 years; 65% were women. Most patients improved outcomes after surgery. Several psychosocial variables were associated with outcomes. Regression analyses indicated lower education, less tangible support, depression, less problem-solving coping, more dysfunctional coping, lower internal locus of control were associated with worse WOMAC scores (R(2) contribution of psychosocial variables for pain 0.07; for function, 0.14). Older age, lower education, depression and less problem-solving coping were associated with poorer total KSRS scores (R(2) contribution of psychosocial variables to total KSRS model 0.09). Psychosocial variables as a set contributed from 25% to 74% of total explained variance across the models tested.
Patients' level of education, tangible support, depression, problem-solving coping, dysfunctional coping and internal locus of control were associated with pain and functional outcomes after knee replacement. The findings suggest that, in addition to medical management, perioperative psychosocial evaluation and intervention are crucial in enhancing knee replacement outcomes.
Treatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus ...nephritis.
In a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation SD) was 37 (12) years, 57% had annual income of <$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error SE, 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive in favor versus negative against), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p < 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence.
An individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis.
Clinicaltrials.gov, NCT02319525.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To examine the impact of a videobooklet patient decision aid supplemented by an interactive values clarification exercise on decisional conflict in patients with knee osteoarthritis (OA) ...considering total knee arthroplasty.
Methods
A total of 208 patients participated in the study (mean age 63 years, 68% female, and 66% white). Participants were randomized to 1 of 3 groups: 1) educational booklet on OA management (control), 2) patient decision aid (videobooklet) on OA management, and 3) patient decision aid (videobooklet) + adaptive conjoint analysis (ACA) tool. The ACA tool enables patients to consider competing attributes (i.e., specific risks/benefits) by asking them to rate a series of paired comparisons. The primary outcome was the decisional conflict scale ranging from 0–100. Differences between groups were analyzed using analysis of variance and Tukey's honestly significant difference tests.
Results
Overall, decisional conflict decreased significantly in all groups (P < 0.05). The largest reduction in decisional conflict was observed for participants in the videobooklet decision aid group (21 points). Statistically significant differences in pre‐ versus postintervention total scores favored the videobooklet group compared to the control group (21 versus 10) and to the videobooklet plus ACA group (21 versus 14; P < 0.001). Changes in the decisional conflict score for the control group compared to the videobooklet decision aid + ACA group were not significantly different.
Conclusion
In our study, an audiovisual patient decision aid decreased decisional conflict more than printed material alone or the addition of a more complex computer‐based ACA tool requiring more intense cognitive involvement and explicit value choices.
Background
Biologic disease‐modifying anti‐rheumatic drugs (DMARDs: referred to as biologics) are effective in treating rheumatoid arthritis (RA), however there are few head‐to‐head comparison ...studies. Our systematic review, standard meta‐analysis and network meta‐analysis (NMA) updates the 2009 Cochrane overview, 'Biologics for rheumatoid arthritis (RA)' and adds new data. This review is focused on biologic or tofacitinib therapy in people with RA who had previously been treated unsuccessfully with biologics.
Objectives
To compare the benefits and harms of biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib versus comparator (placebo or methotrexate (MTX)/other DMARDs) in people with RA, previously unsuccessfully treated with biologics.
Methods
On 22 June 2015 we searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, and Embase; and trials registries (WHO trials register, Clinicaltrials.gov). We carried out article selection, data extraction, and risk of bias and GRADE assessments in duplicate. We calculated direct estimates with 95% confidence intervals (CI) using standard meta‐analysis. We used a Bayesian mixed treatment comparison (MTC) approach for NMA estimates with 95% credible intervals (CrI). We converted odds ratios (OR) to risk ratios (RR) for ease of understanding. We have also presented results in absolute measures as risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB). Outcomes measured included four benefits (ACR50, function measured by Health Assessment Questionnaire (HAQ) score, remission defined as DAS < 1.6 or DAS28 < 2.6, slowing of radiographic progression) and three harms (withdrawals due to adverse events, serious adverse events, and cancer).
Main results
This update includes nine new RCTs for a total of 12 RCTs that included 3364 participants. The comparator was placebo only in three RCTs (548 participants), MTX or other traditional DMARD in six RCTs (2468 participants), and another biologic in three RCTs (348 participants). Data were available for four tumor necrosis factor (TNF)‐biologics: (certolizumab pegol (1 study; 37 participants), etanercept (3 studies; 348 participants), golimumab (1 study; 461 participants), infliximab (1 study; 27 participants)), three non‐TNF biologics (abatacept (3 studies; 632 participants), rituximab (2 studies; 1019 participants), and tocilizumab (2 studies; 589 participants)); there was only one study for tofacitinib (399 participants). The majority of the trials (10/12) lasted less than 12 months.
We judged 33% of the studies at low risk of bias for allocation sequence generation, allocation concealment and blinding, 25% had low risk of bias for attrition, 92% were at unclear risk for selective reporting; and 92% had low risk of bias for major baseline imbalance. We downgraded the quality of the evidence for most outcomes to moderate or low due to study limitations, heterogeneity, or rarity of direct comparator trials.
Biologic monotherapy versus placebo
Compared to placebo, biologics were associated with clinically meaningful and statistically significant improvement in RA as demonstrated by higher ACR50 and RA remission rates. RR was 4.10 for ACR50 (95% CI 1.97 to 8.55; moderate‐quality evidence); absolute benefit RD 14% (95% CI 6% to 21%); and NNTB = 8 (95% CI 4 to 23). RR for RA remission was 13.51 (95% CI 1.85 to 98.45, one study available; moderate‐quality evidence); absolute benefit RD 9% (95% CI 5% to 13%); and NNTB = 11 (95% CI 3 to 136). Results for withdrawals due to adverse events and serious adverse events did not show any statistically significant or clinically meaningful differences. There were no studies available for analysis for function measured by HAQ, radiographic progression, or cancer outcomes. There were not enough data for any of the outcomes to look at subgroups.
Biologic + MTX versus active comparator (MTX/other traditional DMARDs)
Compared to MTX/other traditional DMARDs, biologic + MTX was associated with a clinically meaningful and statistically significant improvement in ACR50, function measured by HAQ, and RA remission rates in direct comparisons. RR for ACR50 was 4.07 (95% CI 2.76 to 5.99; high‐quality evidence); absolute benefit RD 16% (10% to 21%); NNTB = 7 (95% CI 5 to 11). HAQ scores showed an improvement with a mean difference (MD) of 0.29 (95% CI 0.21 to 0.36; high‐quality evidence); absolute benefit RD 9.7% improvement (95% CI 7% to 12%); and NNTB = 5 (95% CI 4 to 7). Remission rates showed an improved RR of 20.73 (95% CI 4.13 to 104.16; moderate‐quality evidence); absolute benefit RD 10% (95% CI 8% to 13%); and NNTB = 17 (95% CI 4 to 96), among the biologic + MTX group compared to MTX/other DMARDs. There were no studies for radiographic progression. Results were not clinically meaningful or statistically significantly different for withdrawals due to adverse events or serious adverse events, and were inconclusive for cancer.
Tofacitinib monotherapy versus placebo
There were no published data.
Tofacitinib + MTX versus active comparator (MTX)
In one study, compared to MTX, tofacitinib + MTX was associated with a clinically meaningful and statistically significant improvement in ACR50 (RR 3.24; 95% CI 1.78 to 5.89; absolute benefit RD 19% (95% CI 12% to 26%); NNTB = 6 (95% CI 3 to 14); moderate‐quality evidence), and function measured by HAQ, MD 0.27 improvement (95% CI 0.14 to 0.39); absolute benefit RD 9% (95% CI 4.7% to 13%), NNTB = 5 (95% CI 4 to 10); high‐quality evidence). RA remission rates were not statistically significantly different but the observed difference may be clinically meaningful (RR 15.44 (95% CI 0.93 to 256.1; high‐quality evidence); absolute benefit RD 6% (95% CI 3% to 9%); NNTB could not be calculated. There were no studies for radiographic progression. There were no statistically significant or clinically meaningful differences for withdrawals due to adverse events and serious adverse events, and results were inconclusive for cancer.
Authors' conclusions
Biologic (with or without MTX) or tofacitinib (with MTX) use was associated with clinically meaningful and statistically significant benefits (ACR50, HAQ, remission) compared to placebo or an active comparator (MTX/other traditional DMARDs) among people with RA previously unsuccessfully treated with biologics.
No studies examined radiographic progression. Results were not clinically meaningful or statistically significant for withdrawals due to adverse events and serious adverse events, and were inconclusive for cancer.
Rituximab for rheumatoid arthritis Lopez‐Olivo, Maria Angeles; Amezaga Urruela, Matxalen; McGahan, Lynda ...
Cochrane database of systematic reviews,
01/2015, Letnik:
2015, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background
Rituximab is a selective, B‐cell depleting, biologic agent for treating refractory rheumatoid arthritis (RA). It is a chimeric monoclonal antibody targeted against CD 20 that is promoted ...as therapy for patients who fail to respond to other biologics. There is evidence to suggest that rituximab is effective and well tolerated when used in combination with methotrexate for RA.
Objectives
To evaluate the benefits and harms of rituximab for the treatment of RA.
Search methods
We conducted a search (until January 2014) in electronic databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science), clinical trials registries, and websites of regulatory agencies. Reference lists from comprehensive reviews were also screened.
Selection criteria
All controlled trials comparing treatment with rituximab as monotherapy or in combination with any disease modifying anti‐rheumatic drug (DMARD) (traditional or biologic) versus placebo or other DMARD (traditional or biologic) in adult patients with active RA.
Data collection and analysis
Two review authors independently assessed the risk of bias and ed data from each study.
Main results
We included eight studies with 2720 patients. For six studies selection bias could not be evaluated and two studies were considered to have low risk of bias. The level of evidence ranged from low to high, but was rated as moderate for most outcomes. We have prioritised reporting of rituximab (two 1000 mg doses) in combination with methotrexate since this is the approved dose and most commonly used combination. We also reported data on other combinations and doses as supplementary information in the results section of the review.
American College of Rheumatology (ACR) 50 response rates were statistically significantly improved with rituximab (two 1000 mg doses) in combination with methotrexate compared with methotrexate alone at 24 to 104 weeks. The RR for achieving an ACR 50 at 24 weeks was 3.3 (95% CI 2.3 to 4.6); 29% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate achieved the ACR 50 compared to 9% of controls. The absolute treatment benefit (ATB) was 21% (95% CI 16% to 25%) with a number needed to treat (NNT) of 6 (95% CI 4 to 9).
At 52 weeks, the RR for achieving clinical remission (Disease Activity Score (DAS) 28 joints < 2.6) with rituximab (two 1000 mg doses) in combination with methotrexate compared with methotrexate monotherapy was 2.4 (95% CI 1.7 to 3.5); 22% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate achieved clinical remission compared to 11% of controls. The ATB was 11% (95% CI 2% to 20%) with a NNT of 7 (95% CI 4 to 13).
At 24 weeks, the RR for achieving a clinically meaningful improvement (CMI) in the Health Assessment Questionnaire (HAQ) (> 0.22) for patients receiving rituximab combined with methotrexate compared to patients on methotrexate alone was 1.6 (95% CI 1.2 to 2.1). The ATB was 24% (95% CI 12% to 36%) with an NNT of 5 (95% CI 3 to 13). At 104 weeks, the RR for achieving a CMI in HAQ (> 0.22) was 1.4 (95% CI 1.3 to 1.6). The ATB was 24% (95% CI 16% to 31%) with a NNT of 5 (95% CI 3 to 7).
At 24 weeks, the RR for preventing radiographic progression in patients receiving rituximab (two 1000 mg doses) in combination with methotrexate was 1.2 (95% CI 1.0 to 1.4) compared to methotrexate alone; 70% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate had no radiographic progression compared to 59% of controls. The ATB was 11% (95% CI 2% to 19%) and the NNT was 10 (95% CI 5 to 57). Similar benefits were observed at 52 to 56 weeks and 104 weeks.
Statistically significantly more patients achieved a CMI on the physical and mental components of the quality of life, measured by the Short Form (SF)‐36, in the rituximab (two 1000 mg doses) in combination with methotrexate‐treated group compared with methotrexate alone at 24 to 52 weeks (RR 2.0, 95% CI 1.1 to 3.4; NNT 4, 95% CI 3 to 8 and RR 1.4, 95% CI 1.1 to 1.9; NNT 8, 95% CI 5 to 19, respectively); 34 and 13 more patients out of 100 showed an improvement in the physical component of the quality of life measure compared to methotrexate alone (95% CI 5% to 84%; 95% CI 7% to 8%, respectively).
There was no evidence of a statistically significant difference in the rates of withdrawals because of adverse events or for other reasons (that is, withdrawal of consent, violation, administrative, failure to return) in either group. However, statistically significantly more people receiving the control drug withdrew from the study compared to those receiving rituximab (two 1000 mg doses) in combination with methotrexate at all times (RR 0.40, 95% CI 0.32 to 0.50; RR 0.61, 95% CI 0.40 to 0.91; RR 0.48, 95% CI 0.28 to 0.82; RR 0.58, 95% CI 0.45 to 0.75, respectively). At 104 weeks, 37% withdrew from the control group and 20% withdrew from the rituximab (two 1000 mg doses) in combination with methotrexate group. The absolute risk difference (ARD) was ‐20% (95% CI ‐34% to ‐5%) with a number needed to harm (NNH) of 7 (95% CI 5 to 11).
A greater proportion of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate developed adverse events after their first infusion compared to those receiving methotrexate monotherapy and placebo infusions (RR 1.6, 95% CI 1.3 to 1.9); 26% of those taking rituximab plus methotrexate reported more events associated with their first infusion compared to 16% of those on the control regimen with an ARD of 9% (95% CI 5% to 13%) and a NNH of 11 (95% CI 21 to 8). However, no statistically significant differences were noted in the rates of serious adverse events.
Authors' conclusions
Evidence from eight studies suggests that rituximab (two 1000 mg doses) in combination with methotrexate is significantly more efficacious than methotrexate alone for improving the symptoms of RA and preventing disease progression.
Objectives This study compared opioid prescribing among ambulatory visits with systemic autoimmune/inflammatory rheumatic diseases (SARDs) or without and assessed factors associated with opioid ...prescribing in SARDs. Methods This cross‐sectional study used the National Ambulatory Medical Care Survey between 2006 and 2019. Adult (≥18 years) visits with a primary diagnosis of SARDs, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or systemic lupus erythematosus were included in the study. Opioid prescribing was compared between those with vs without SARDs using multivariable logistic regression accounting for the complex survey design and adjusting for predisposing, enabling, and need factors within Andersen's Behavioral Model of Health Services Use. Another multivariable logistic regression examined the predictors associated with opioid prescribing in SARDs. Results Annually, an average of 5.20 million (95% confidence interval CI 3.58–6.82) visits were made for SARDs, whereas 780.14 million (95% CI 747.56–812.72) visits were made for non‐SARDs. The SARDs group was more likely to be prescribed opioids (22.53%) than the non‐SARDs group (9.83%) (adjusted odds ratio aOR 2.65; 95% CI 1.68–4.18). Among the SARDs visits, patient age from 50 to 64 (aOR 1.95; 95% CI 1.05–3.65 relative to ages 18–49) and prescribing of glucocorticoids (aOR 1.75; 95% CI 1.20–2.54) were associated with an increased odd of opioid prescribing, whereas private insurance relative to Medicare (aOR 0.50; 95% CI 0.31–0.82) was associated with a decreased odds of opioid prescribing. Conclusion Opioid prescribing in SARDs was higher compared to non‐SARDs. Concerted efforts are needed to determine the appropriateness of opioid prescribing in SARDs.
Background
Biologic disease‐modifying anti‐rheumatic drugs (biologics) are highly effective in treating rheumatoid arthritis (RA), however there are few head‐to‐head biologic comparison studies. We ...performed a systematic review, a standard meta‐analysis and a network meta‐analysis (NMA) to update the 2009 Cochrane Overview. This review is focused on the adults with RA who are naive to methotrexate (MTX) that is, receiving their first disease‐modifying agent.
Objectives
To compare the benefits and harms of biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib versus comparator (methotrexate (MTX)/other DMARDs) in people with RA who are naive to methotrexate.
Methods
In June 2015 we searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE and Embase; and trials registers. We used standard Cochrane methods. We calculated odds ratios (OR) and mean differences (MD) along with 95% confidence intervals (CI) for traditional meta‐analyses and 95% credible intervals (CrI) using a Bayesian mixed treatment comparisons approach for network meta‐analysis (NMA). We converted OR to risk ratios (RR) for ease of interpretation. We also present results in absolute measures as risk difference (RD) and number needed to treat for an additional beneficial or harmful outcome (NNTB/H).
Main results
Nineteen RCTs with 6485 participants met inclusion criteria (including five studies from the original 2009 review), and data were available for four TNF biologics (adalimumab (six studies; 1851 participants), etanercept (three studies; 678 participants), golimumab (one study; 637 participants) and infliximab (seven studies; 1363 participants)) and two non‐TNF biologics (abatacept (one study; 509 participants) and rituximab (one study; 748 participants)).
Less than 50% of the studies were judged to be at low risk of bias for allocation sequence generation, allocation concealment and blinding, 21% were at low risk for selective reporting, 53% had low risk of bias for attrition and 89% had low risk of bias for major baseline imbalance. Three trials used biologic monotherapy, that is, without MTX. There were no trials with placebo‐only comparators and no trials of tofacitinib. Trial duration ranged from 6 to 24 months. Half of the trials contained participants with early RA (less than two years' duration) and the other half included participants with established RA (2 to 10 years).
Biologic + MTX versus active comparator (MTX (17 trials (6344 participants)/MTX + methylprednisolone 2 trials (141 participants))
In traditional meta‐analyses, there was moderate‐quality evidence downgraded for inconsistency that biologics with MTX were associated with statistically significant and clinically meaningful benefit versus comparator as demonstrated by ACR50 (American College of Rheumatology scale) and RA remission rates. For ACR50, biologics with MTX showed a risk ratio (RR) of 1.40 (95% CI 1.30 to 1.49), absolute difference of 16% (95% CI 13% to 20%) and NNTB = 7 (95% CI 6 to 8). For RA remission rates, biologics with MTX showed a RR of 1.62 (95% CI 1.33 to 1.98), absolute difference of 15% (95% CI 11% to 19%) and NNTB = 5 (95% CI 6 to 7). Biologics with MTX were also associated with a statistically significant, but not clinically meaningful, benefit in physical function (moderate‐quality evidence downgraded for inconsistency), with an improvement of HAQ scores of ‐0.10 (95% CI ‐0.16 to ‐0.04 on a 0 to 3 scale), absolute difference ‐3.3% (95% CI ‐5.3% to ‐1.3%) and NNTB = 4 (95% CI 2 to 15).
We did not observe evidence of differences between biologics with MTX compared to MTX for radiographic progression (low‐quality evidence, downgraded for imprecision and inconsistency) or serious adverse events (moderate‐quality evidence, downgraded for imprecision). Based on low‐quality evidence, results were inconclusive for withdrawals due to adverse events (RR of 1.32, but 95% confidence interval included possibility of important harm, 0.89 to 1.97). Results for cancer were also inconclusive (Peto OR 0.71, 95% CI 0.38 to 1.33) and downgraded to low‐quality evidence for serious imprecision.
Biologic without MTX versus active comparator (MTX 3 trials (866 participants)
There was no evidence of statistically significant or clinically important differences for ACR50, HAQ, remission, (moderate‐quality evidence for these benefits, downgraded for imprecision), withdrawals due to adverse events,and serious adverse events (low‐quality evidence for these harms, downgraded for serious imprecision). All studies were for TNF biologic monotherapy and none for non‐TNF biologic monotherapy. Radiographic progression was not measured.
Authors' conclusions
In MTX‐naive RA participants, there was moderate‐quality evidence that, compared with MTX alone, biologics with MTX was associated with absolute and relative clinically meaningful benefits in three of the efficacy outcomes (ACR50, HAQ scores, and RA remission rates). A benefit regarding less radiographic progression with biologics with MTX was not evident (low‐quality evidence). We found moderate‐ to low‐quality evidence that biologic therapy with MTX was not associated with any higher risk of serious adverse events compared with MTX, but results were inconclusive for withdrawals due to adverse events and cancer to 24 months.
TNF biologic monotherapy did not differ statistically significantly or clinically meaningfully from MTX for any of the outcomes (moderate‐quality evidence), and no data were available for non‐TNF biologic monotherapy.
We conclude that biologic with MTX use in MTX‐naive populations is beneficial and that there is little/inconclusive evidence of harms. More data are needed for tofacitinib, radiographic progression and harms in this patient population to fully assess comparative efficacy and safety.
BackgroundImmune checkpoint inhibitors (ICI) can cause off-target inflammatory and immune-related adverse events (irAE). Conceivably, COVID-19 vaccination could trigger an inflammatory and immune ...response that could induce or aggravate irAE.MethodsThe objective of this systematic review is to appraise the efficacy and safety of COVID-19 vaccination in patients with cancer treated with ICI. The literature search was performed in PubMed and Embase in English from December 2019 to February 2022. The review included clinical trials, observational cohort studies, case series, and case reports reporting on the clinical efficacy and safety of COVID-19 vaccines on patients with cancer treated with ICI. Outcomes of interest included seroconversion, SARS-CoV-2 infection rate, severe COVID-19, COVID-19 mortality rate. Incidence of ICI irAEs was also ascertained as well as vaccine adverse events. A meta-analysis was conducted to estimate the pooled effect sizes of the outcomes when possible, using random effects models.ResultsOverall, 19 studies were included for the analysis (n=10 865 with 2477 receiving ICI). We analyzed 15 cohort studies, 1 cross-sectional study, and 3 case reports. There were no statistically significant differences in seroconversion rates after the second dose of the vaccine when comparing patients with cancer receiving ICI with patients without cancer (risk ratio, RR 0.97, 95% CI 0.92 to 1.03) or with patients with cancer without active treatment (RR 1.00, 95% CI 0.96 to 1.04). There was a higher probability of seroconversion in patients with cancer treated with ICI compared with patients with cancer treated with chemotherapy (RR 1.09, 95% CI 1.00 to 1.18). In a single study in patients receiving ICI, no differences were observed in risk of irAE between those receiving inactivated vaccine and those unvaccinated (pneumonitis RR 0.88, 95% CI 0.33 to 2.3; rash RR 1.03, 95% CI 0.66 to 1.62; arthralgia RR 0.94, 95% CI 0.51 to 1.75). There were no studies for other types of vaccines comparing vaccinated vs not vaccinated in patients treated with ICI. The most common vaccine-related adverse events were local pain or fatigue. Overall, the quality of evidence was rated as very low.ConclusionCOVID-19 vaccination appears to be effective and safe in patients with cancer receiving ICI.
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