non-TNF Biologics Research Articles

Primary Non-Response to Tumor Necrosis Factor Antagonists is Associated with Inferior Response to Second-line Biologics in Patients with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis.

We sought to analyze whether response to a second-line biologic varies depending on the reason for discontinuation of the primary anti-TNF agent (primary non-response [PNR], secondary loss of response [LOR] after initial response, or intolerance), through a systematic review and meta-analysis. Through a systematic search through May 31, 2017, we identified eight randomized controlled trials [RCTs] of biologics in patients with IBD with prior exposure to anti-TNF agents, that stratified response to second-line therapy by reason for discontinuing primary anti-TNF therapy [PNR vs. LOR vs. intolerance]. We estimated relative risk [RR] (and 95% confidence interval [CI]) of achieving clinical remission in patients with PNR as compared with patients with LOR, and intolerance, through random effects meta-analysis. As compared with patients who discontinued prior anti-TNF due to intolerance, patients with prior PNR were 24% less likely to achieve remission with second-line biologics (RR,0.76 [0.61-0.96]). As compared with patients who discontinued prior anti-TNF due to LOR, patients with prior PNR were 27% less likely to achieve remission with induction therapy with second-line biologics (RR,0.73 [0.56-0.97]), particularly to ustekinumab (RR,0.64 [0.52-0.80]). There was no difference in response to vedolizumab in patients with prior PNR or LOR to anti-TNF agents (RR,1.16 [0.85-1.58]). Patients with PNR to anti-TNF agents are less likely to respond to second-line non-TNF biologics, as compared with patients who discontinued therapy due to secondary LOR or intolerance. This may be attributed to underlying pharmacokinetics and pharmacodynamics of anti-TNF agents in patients with PNR.

Systematic Literature Review and Meta-analysis of Tumor Necrosis Factor–Alpha Experienced Rheumatoid Arthritis

PurposeThe goal of this study was to compile all available evidence regarding the efficacy of tumor necrosis factor–α (TNF) inhibitors, non-TNF biologics, and tofacitinib for TNF-experienced patients who have rheumatoid arthritis (RA). MethodsA systematic literature review of MEDLINE, EMBASE, and rheumatology conference abstracts was performed to identify observational studies and randomized controlled trials (RCTs) reporting American College of Rheumatology response rates (ACR 20/50/70) for adult patients with RA who switched from at least 1 TNF to another TNF or a non-TNF therapy. A direct random effects meta-analysis was performed to evaluate ACR 20/50/70 response rates for TNF and non-TNF therapies. Separate analyses were conducted among 3-, 6-, and 12-month observational studies and for 6-month RCTs. FindingsA total of 18 observational studies and 6 RCTs were selected. Among 3-month observational studies, the percentages of ACR20/50/70 responders switching to another TNF were similar to those switching to a non-TNF biologic (ACR20, 54.5% vs 58.6%; ACR50, 33.3% vs 33.3%; and ACR70, 13.0% vs 14.6%, respectively). Among 6-month observational studies, the percentages of TNF ACR20/50/70 responders were higher than those of non-TNF responders (ACR20, 67.7% vs 50.4%; ACR50, 50.4% vs 26.6%; and ACR70, 24.9% vs 11.6%). Among 6-month RCTs, the percentages of non-TNF biologic ACR20/50/70 responders were similar to those in the 6-month non-TNF observational studies (ACR20, 50.7% vs 50.4%; ACR50, 27.5% vs 26.6%; and ACR70, 11.9% vs 11.6%). For 12-month observational studies, TNF biologic ACR20/50/70 percentages were higher than those of non-TNF therapies (ACR20, 72.2% vs 57.0%; ACR50, 42.1% vs 28.9%; and ACR70, 22.9% vs 10.0%). ImplicationsFor TNF-experienced patients with RA, subsequent TNF therapy and non-TNF biologic therapy have comparable efficacy.

Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis.

Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis.

Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.

Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.

Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis.

Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis.

Malignancies of the skin and immunomodulatory antirheumatic therapy

For the clinical practice there is uncertainty as to what degree the therapeutic immunomodulation of rheumatoid arthritis (RA) is associated with a weakening of protective tumor immunity. Neoplasms of the skin in particular are known to exhibit increased incidence rates in association with therapeutic immunosuppression in transplantation medicine; however, the immunosuppression required for the prevention of allogenic graft rejection is much more intensive and thus not directly transferable to the potential risks for an onset or relapse of melanoma or non-melanoma skin cancers (NMSC), e. g. spinocellular and basal cell carcinomas in association with the antirheumatic treatment of RA. This review covers the association of RA and its pharmacotherapy with conventional synthetic (cs) and biologic disease-modifying antirheumatic drugs (DMARD) on the basis of a systematic literature search. The incidence rates of NMSC are twice as high in biologic-naive RA patients compared to the general population, whereas the respective incidence rates for melanoma do not differ. A biologic treatment with tumor necrosis factor (TNF) blockers compared with administration of csDMARD only has a minor, if any effect on the increase of NMSC risk but is associated with a trend towards an elevated incidence rate of new onset melanoma although significance level was not reached in all of the reviewed studies. The data on non-TNF blocking biologics is sparse. Accordingly, it is inappropriate to draw any strong conclusions on potentially associated skin cancer risks from the present lack of safety signals. The consideration of individual risk factors, recommendations on sufficient UV protection and regular skin monitoring may serve to improve the safety of DMARD therapy in RA.

Targeting inflammation in the prevention of cardiovascular disease in patients with inflammatory arthritis

Patients with inflammatory arthritis have increased risk of cardiovascular diseases (CVDs) compared with the general population. Subclinical carotid atherosclerosis and increased arterial stiffness are also common in these patients, which may serve as surrogate end points for cardiovascular (CV) events in clinical trials. Although exact mechanisms are still unclear, persistent systemic inflammation in patients with inflammatory arthritis may contribute to the development of CVD. Dysregulated innate immunity pathways in these patients may also play a role in accelerating atherosclerosis. During the last decade, effective suppression of inflammation by biological disease-modifying antirheumatic drugs has improved the disease outcome dramatically in patients with inflammatory arthritis. Growing evidence suggests that antitumor necrosis factor (TNF) therapy may prevent CVD in patients with rheumatoid arthritis. Nonetheless, data on non-TNF biologics are limited. Whether anti-TNF therapy may prevent CVD in patients with spondyloarthritis also remained unclear. In this review, we summarized the effect of both anti-TNF and non-TNF biologics on the CV system, including traditional CVD risk factors, endothelial function, arterial stiffness, subclinical atherosclerosis, and clinical CVD in patients with inflammatory arthritis.

Comparative effectiveness of cycling of tumor necrosis factor-α (TNF-α) inhibitors versus switching to non-TNF biologics in rheumatoid arthritis patients with inadequate response to TNF-α inhibitor using a Bayesian approach

Alternative tumor necrosis factor-α (TNF-α) inhibitors and non-TNF biologics are available as treatment options for rheumatoid arthritis patients who exhibit inadequate response to TNF-α inhibitor (TNF-IR patients). These agents have considerable efficacy compared with placebo, but head-to-head comparisons among these agents have not been performed. The objective of this study was to use Bayesian approach to compare the effectiveness of cycling TNF-α inhibitors versus switching to non-TNF biologics in TNF-IR patients. A systematic review was conducted using MEDLINE and Cochrane library. Key endpoints were the American College of Rheumatology (ACR) responses of 20/50/70 and the health assessment questionnaire (HAQ) score change at six months. Bayesian outcomes were calculated as the probability that OR is greater than one and HAQ score change difference is less than zero. Compared with TNF-α inhibitors, non-TNF biologics were associated with higher ACR response rates; in ACR20, the OR was 1.639 for abatacept [P(OR > 1) = 90.7 %], 1.871 for rituximab [P(OR > 1) = 96.2 %] and 3.52 for tocilizumab [P(OR > 1) = 99.9 %]. Similar trends were shown in the HAQ change comparison; the median differences (MD) were -0.259 for abatacept [P(MD < 0) = 100 %], -0.160 for rituximab [P(MD < 0) = 98.2 %], and -0.200 for tocilizumab [P(MD < 0) = 99.3 %]. In conclusion, switching to non-TNF biologics was more effective than cycling TNF-α inhibitor in TNF-IR patients.

FRI0108 Risk for herpes zoster after treatment with biologic and synthetic disease modifying agents for rheumatoid arthritis

BackgroundHerpes zoster (HZ) is an opportunistic infection with a high incidence in Rheumatoid Arthritis (RA) patients. There are contradictory data regarding the risk of HZ associated with treatment with biologic...

AB0453 Retention rate of the anti-TNF biologics in the treatment of rheumatic diseases and predictive factors for drug withdrawal: Data from the hong kong biologics registry

ObjectivesTo study the retention rate of the anti-TNF biologics in the treatment of rheumatic diseases and the associated factors for drug withdrawalMethodsThe Hong Kong Biologics Registry was established in 2005....

Ten years with biologics: to whom do data on effectiveness and safety apply?

During the past decade, the position of biologics in the therapeutic armamentarium, the number of approved indications and the number of available biologics have changed. Available data on (long-term) safety might thus pertain to patient populations not comparable with contemporary patients. The aim of this study was to assess the extent to which contemporary patients who start or switch biologic therapies are comparable with those patients who gave rise to the currently available data on effectiveness and safety. We identified all adult patients with RA (n=9612), PsA (n=1417) and other SpA (n=1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation. Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite <50% drug retention at 5 years, most patients remained exposed to some biologic. The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.