Justina Petrullo

Drug manufacturer payments to ophthalmologists were linked with the selection of higher-cost therapies for age-related macular degeneration (ARMD) that presents as a factor in heightened Medicare, and biosimilars can act as a possible cost-saving solution in the future, according to 

Roughly 4 million beneficiaries of traditional Medicare used 

 in 2020, where total payments hit $38.5 billion. The entrance of new, nonbiosimilar drugs between 2016 and 2020 accounted for $12 billion of the increased spending (80%), while price increases and use shifts among existing single-source brand drugs accounted for the leftover spending increase.

Reference aflibercept (Eylea) and ranibizumab (Lucentis) are amid the costliest Medicare Part B drugs, even though off-label use of lower-cost bevacizumab is not clinically inferior.

Researchers aimed to evaluate the link between manufacturer payments to ophthalmologists and ARMD treatment choice and to pinpoint ophthalmologist-level qualities linked with prescribing lower-cost ARMD therapies.

There exist 3 anti-vascular epithelial growth factor treatments that are equally recommended by the American Academy of Ophthalmology for ARMD. ARMD is the leading cause of blindness in adults aged 50 and older, and it impacts approximately 19.5 million people in the US.

This was a retrospective cross-sectional study of longitudinal (2013-2019) Medicare Part B data that was conducted from December 2021 to December 2022. The study included ophthalmologists who prescribed aflibercept, ranibizumab, or bevacizumab for ARMD treatment of Medicare Part B beneficiaries. 

, there are 4 biosimilars in the United States (US) and 8 approved biosimilars in the European Union (EU). For ranbizumab, there are 2 approvals in the US and 3 in the EU. At present, there are no aflibercept biosimilars in the US and 1 approved product in the EU (

). Reference ranibizumab (Cimerli) came out as the first ranibizumab biosimialr to receive an interchangeable designation in 

Celltrion was granted an approval from the Therapeutic Goods Administration (the FDA equivalent in Australia), for its bevacizumab biosimilar (Vegzelma), which 

. It’s currently indicated for some cancers, but not ARMD, though some providers use it off-label.

The percentage of bevacizumab prescribed by ophthalmologists among all ARMD therapies comprised the primary outcome of the present study. Regression analysis evaluated variation in bevacizumab prescribing. 

“Savings were estimated by projecting the change in bevacizumab use had ophthalmologists not accepted manufacturer payments, controlling for all ophthalmologist and patient characteristics and comparing with observed use and costs,” the researchers continued.

A total of 21584 ophthalmologists comprised the cohort. Ophthalmologists who accepted payments from manufacturers were significantly less likely to prescribe bevacizumab (28.0% of patients) compared with those who did not accept payments from manufacturers (45.8%). Ophthalmologists who encountered dual-eligible beneficiaries had higher bevacizumab prescribing (50.0%) in the highest quartile vs 36.1% in the lowest quartile; 

 < .001), while ophthalmologists who saw patients with higher mean beneficiary risk scores had lower bevacizumab use 38.0% in the highest quartile vs 48.2% in the lowest quartile; 

Manufacturer payments were linked with less prescribing of lower-cost therapies, and ophthalmologists who accepted manufacturer payments prescribed lower-cost therapies almost half as often as ophthalmologists who did not accept manufacturer payments (28.0% vs 45.8%).

“The choice to use a more expensive therapy over bevacizumab cost an additional $5231.35 per Medicare beneficiary per year. For beneficiaries without a Medigap policy to cover their 20% coinsurance, the out-of-pocket cost would be $1046.27,” said the researchers.

Ophthalmologists with a higher percentage of dual-eligible beneficiaries in their patient population were significantly more likely to prescribe bevacizumab.

Those who saw patients with a higher risk score were significantly less likely to prescribe bevacizumab, and relatedly, ophthalmologists with older patients were, on average, less likely to prescribe bevacizumab.

Manufacturer payment models that urge ophthalmologists to choose lower-cost therapies need to be developed.

This study has some limitations. Differences in billing for off-label bevacizumab use might impact the estimates. Secondly, the patient qualities mirrored the entire patient mix observed by the ophthalmologist, not just those who received ARMD treatment.

“Given that ophthalmologists appeared to gain greater profits when choosing higher-cost therapies, policymakers should counter this incentive by developing manufacturer payment models that encourage ophthalmologists to choose lower-cost therapies,” concluded the researchers.

Dickson SR, James KE. Medicare part B spending on macular degeneration treatments associated with manufacturer payments to ophthalmologists. 

 Published online September 8, 2023. doi:10.1001/jamahealthforum.2023.2951

Articles

Drug maker payments to ophthalmologists were associated with the choice of higher-cost therapies for age-related macular degeneration (ARMD) that could increase Medicare costs, but biosimilars could help.

Higher-Cost Therapies for ARMD Could Contribute to Heightened Medicare Costs; Biosimilars Could Help

Hi, I’m Justina Petrullo for The Center for Biosimilars®, your resource for clinical, regulatory, business, and policy news in the rapidly changing world of biosimilars.

Here are the top 5 biosimilar articles for the week of September 18th, 2023.

 between antidrug antibodies and nonresponse to biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA).

Number 4: Although removing the requirement for clinical efficacy testing for biosimilar approval would reduce development costs of biosimilars, representatives from several biosimilar manufacturers argued in the 

second day of the FDA’s development workshop

 that clinical outcomes will not be affected.

Association for Accessible Medicines (AAM)

 highlighted the value of biosimilars and generics, revealing that lower-cost versions of originator products accumulated $408 billion for the US health care system in 2022.

Number 2: Growing use of innovator biologics, including those with biosimilar competition, has led to increased 

 featuring regulators from around the world provided the regulatory perspective on how each government determines whether a biosimilar is clinically equivalent to their reference product, highlighting the science behind their development guidelines.

To read all of these articles and more, visit 

Videos

Here are the top 5 biosimilar articles for the week of September 18, 2023.

The Top 5 Biosimilar Articles for the Week of September 18

Here are the top 5 biosimilar articles for the week of September 11th, 2023.

Number 5: Switching from reference to biosimilar adalimumab was found to be 

, researchers cautioned that female patients may be at higher risk of discontinuation compared with their male counterparts.

 of the first 10 drugs chosen for price negotiation under the Inflation Reduction Act, including 3 biologics with no biosimilar competition.

Number 3: Perhaps the most significant development in the pharmaceutical industry in decades, crops of biosimilars are being 

. What lies next, in terms of legislation and the impact on pharmacists, remains to be seen.

 and positive recommendations for 2 biosimilars in Europe brought hope for more affordable biologics around the world. However, another settlement for a US ustekinumab biosimilar showcased that some barriers remain.

, a new subsidiary that will work with manufacturers to commercialize and coproduce biosimilars, beginning with an adalimumab product.

Here are the top 5 biosimilar articles for the week of September 11, 2023.

The Top 5 Biosimilar Articles for the Week of September 11

Medicare Part B drug expenditures have grown in recent years, which is likely to endure due to the growing use and availability of innovator 

Researchers aimed to evaluate the extent to which Medicare Part B spending growth was linked with changes in price vs quantity, and how these trends intermingled with marketplace entry of new drugs.

Almost 4 million beneficiaries of traditional Medicare used Part B-covered drugs in 2020, where total payments reached $38.5 billion. Even though total Part B spending was almost one-fifth of Medicare’s outpatient prescription drug benefit (Part D) in the same year. Part B has seen sustained increases, and beneficiaries of traditional Medicare encounter 20% cost sharing for most Part B drugs.

Cloud Pricing Stock Vector Illustration | © 123RF Stock Photos

The cross-sectional study quantified the degree of spending concentration and the link between price and use of Part B drugs among fee-for-service Medicare beneficiaries. Use and spending data for separately payable Part B drugs were included in this study, and source data were aggregated to the drug-year level and reported from 2016 to 2020.

Descriptive decomposition and index analyses quantified the relative association, separately, of price and use changes for present single-source drugs, existing drugs that met competition, and new drugs that came onto the market. Data analysis was undertaken from June to December 2022.

The main outcomes consisted of Part B spending by the fee-for-service Medicare program and beneficiaries, and use, defined as dosage units and beneficiary drug use.

A total of 535 unique Part B drug products were included in the study. During the period of 2016 to 2020, 15 or fewer products made up half of all Part B drug expenditures. The 7 drugs that made up the top 25% of spending was extremely consistent over time and were all biologics. Part B drug products that cost $1.85 or less per administration made up over 505 of the doses administered in 2020. Part B drug spending grew by $15 billion from 2016 to 2020.

The emergence of new, nonbiosimilar drugs during this time accounted for $12 billion of the increased spending (80%), while use shifts and price increases among present single-source brand drugs accounted for the leftover increase in spending. Part B spending lowered among the subset of existing drugs encountering generic or biosimilar competition. Among single-source drugs on the market in 2016, the index that varied dosage units surpassed the index that varied price in all years, confirming that changes in use were linked with more with spending growth for those drugs.

Three of the 7 drugs making up the top quarter of Medicare Part B spending every year have biosimilars on the 

Rituxan (reference rituximab)—3 biosimilars are currently on the US market, with the first that launched in November 2019

Neulasta (reference pegfilgrastim)—6 biosimilars are on the US market presently, and the first launched in June 2018

Remicade (reference infliximab)—4 approved biosimilars exist in the US, but only 3 have launched; the first launch was in November 2016

Related analyses had shown that most biologic drugs don’t have biosimilar competitors in the current market and the pipeline. High-spending, single-source drugs that have been on the market for years will probably be subject to 

 under the Inflation Reduction Act of 2022.

“Negotiations may curb future increases in the Medicare payment limit,” the researchers emphasized.

Compared with existing products, drugs more recently brought to market were linked with Part B spending increases in the past few years. Almost all increases in Part B drug spending over the last 10 years were associated with biologics.

“Although CMS cannot negotiate prices of newly marketed drugs, prices are subject to the inflation rebate,” continued the researchers.

Additionally, the researchers also found that the price of single-source drugs made up a fairly small share of the overall spending increase and suggests that the association of the rebate previsions with spending might be muted.

Analyses also suggest that policies targeting the highest-selling drugs have the most potential to reduce spending, while those targeting price jumps will have a smaller influence.

One notable limitation of this study is that drug spending and use for Medicare Advantage, which makes up over 40% of total Medicare enrollment in 2020, was not taken into consideration by these data.

“The findings [of this study] suggest that policies targeting top-selling drugs may have greater potential to curb Part B drug spending than those targeting price increases,” concluded the researchers.

Hyland MF, Sachs RM, Robillard L, Hayford TB, Bai G. Spending on and use of clinician-administered drugs in medicare. 

. Published online September 8, 2023. doi:10.1001/jamahealthforum.2023.2941

Growing use of innovator biologics, including those with biosimilar competition, has led to increased Medicare Part B drug expenditures, with the trend unlikely to stop.

Biologic Availability Contributes to Medicare Part B Drug Expenditure Growth

Prospective cohort study results suggest a link between antidrug antibodies and nonresponse to biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with 

Supervising antidrug antibodies could be considered in the treatment of these patients, especially those who don’t respond to biologic RA drugs.

There are conflicting data on the link of antidrug antibodies with response to bDMARDs in RA, so researchers aimed to analyze the link of antidrug antibodies with response to treatment for RA.

RA affects joint linings, leading to painful swelling for many patients. Over long periods of time, the inflammation associated with RA can cause bone erosion and joint deformity.

bDMARDS are recommended as a second-line treatment for RA, but the retention rate is low, with between 40% and 60% of patients maintaining treatment after 2 years. Antidrug antibodies are one of the factors linked with the ineffectiveness of these treatments, and these antibodies directed against biologic drugs might play a part in diminished drug concentration and bDMARD effectiveness loss.

This study evaluated data from the Anti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk of Immunization in Rheumatoid Arthritis Patients multicentric, open, prospective study of patients with RA from 27 recruiting centers in France, Italy, the Netherlands, and the United Kingdom. Eligible patients were 18 years old or older, had RA diagnosis, and were starting a new bDMARD. Recruitment was from March 3, 2014, to June 21, 2016. The study was finished in June 2019, and data were analyzed in June 2022.

Patients were treated with a new bDMARD: adalimumab, infliximab grouped as anti-tumor necrosis factor (TNF) monoclonal antibodies (mAbs) as well as etanercept, tocilizumab, and rituximab according to the selection of the treating physician.

The primary outcome was the association of antidrug antibody positivity with European Alliance of Associations for Rheumatology (EULAR) response to treatment at month 12 reviewed through univariate logistic regression.

Identification of antidrug antibody serum levels was conducted at months 1, 3, 6, 12, and 15 to 18 using electrochemiluminescence (Meso Scale Discovery) and drug concentration for anti-TNF mAbs, and etanercept in the serum was measured using enzyme-linked immunosorbent assay.

A total of 230 patients (mean [SD] age, 54.3 [13.7] years; 77.0% female) were evaluated. At month 12, antidrug antibody positivity was 38.2% in patients who were treated with anti-TNF mAbs, 6.1% with etanercept, 50.0% with rituximab, and 20.0% with tocilizumab. There was an inverse association between antidrug antibody positivity (odds ratio [OR], 0.19; 95% CI, 0.09-0.38; 

 < .001) aimed against all biologic drugs and EULAR response at month 12.

Analyzing all the visits starting at month 6 using generalized estimating equation models established the inverse association between antidrug antibody positivity and EULAR response (OR, 0.35; 95% CI, 0.18-0.65; 

 < .001). A similar link was found for tocilizumab alone (OR, 0.18; 95% CI, 0.04-0.83; 

= .03). In the multivariable analysis, antidrug antibodies, body mass index, and rheumatoid factor were independently inversely associated with response to treatment.

There was a significantly higher drug concentration of anti-TNF mAbs in patients with antidrug antibody-negative vs antidrug antibody-positive status (mean difference, −9.6; 95% CI, −12.4 to −6.9 mg/L; 

 < 001). Drug concentrations of etanercept (mean difference, 0.70; 95% CI, 0.2-1.2 mg/L; 

 = .005) and adalimumab (mean difference, 1.8; 95% CI, 0.4-3.2 mg/L; 

 = .01) were lower in nonresponders over responders. Methotrexate comedication at baseline was inversely linked with antidrug antibodies (OR, 0.50; 95% CI, 0.25-1.00; 

Using the generalized estimating equation model, the researchers demonstrated for the first time an inverse association between antidrug antibodies aimed against tocilizumab and treatment response. These antibodies were less prevalent than those against anti-TNF mAbs, but in the 20% of patients with antidrug antibody-positive status who were treated with tocilizumab, they were linked with response to treatment.

This study established the high incidence of antidrug antibodies against several bDMARDs and the inverse association of antidrug antibodies with EULAR response and found no link between the frequently seen anti-rituximab antidrug antibodies and response to treatment.

It also emphasized the link between antidrug antibodies and lower drug concentration of anti-TNF mAbs and lower concentration with nonresponse of adalimumab and etanercept.

This study has some limitations. First, it showed an association when all biologic drugs were analyzed together, but the study was not powered to demonstrate a link for each drug class. But, the ORs in all analyses with individual drug classes showed similar results or patterns. Second, there was a considerable proportion of patients in the unclassified category since the researchers defined these patients firmly as those lacking 1 or more antidrug antibody measurements for the analysis of response at month 12.

“In this prospective cohort study of patients with RA, response to biologic drugs was inversely associated with antidrug antibody positivity. Monitoring of antidrug antibodies could be considered in the personalized management of patients with RA, particularly nonresponders,” concluded the researchers.

Bitoun S, Hässler S, Ternant D, et al. Response to biologic drugs in patients with rheumatoid arthritis and antidrug antibodies. 

 Published online July 12, 2023. doi:10.1001/jamanetworkopen.2023.23098

Study results suggest an association between antidrug antibodies and nonresponse to biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA).

Link Between Antidrug Antibodies and bDMARDs Nonresponse in Patients With RA

Here are the top 5 biosimilar articles for the week of September 4th, 2023.

 for the first 6 months of 2023 reached $22.7 million, a nearly 600% year-over-year increase.

 industry’s future, with the approval of the first neurology biosimilar, growth projections from company quarterly expense reports, and several analyses about the health of the market.

reacted to CMS' list of the first 10 drugs

 chosen for price negotiation under the Inflation Reduction Act (IRA), including 3 biologics with no biosimilar competition.

Number 2: Single switching between approved biologics and biosimilars of tumor necrosis factor inhibitors (TNFis) were found to be 

Number 1: Stelara (ustekinumab) and Enbrel (etanercept), 2 originator medications that will face biosimilar competition within the next decade, were among the 10 preliminary drugs 

 under the Inflation Reduction Act (IRA).

Here are the top 5 biosimilar articles for the week of September 4, 2023.

The Top 5 Biosimilar Articles for the Week of September 4

On this episode, we’re going to be giving an overview of some of the biggest stories in the business space regarding biosimilars, like the approval of the first neurology biosimilar, growth projections from company quarterly expense reports, and some analyses about the health of the market.

Stelara and Enbrel Chosen for IRA Price Negotiation

Biocon Biosimilar Quarterly Sales Up 106%

STADA Earnings Project Record Breaking Profits for 2023

Despite Global Increase in Amjevita Sales, US Sales Dropped 63%

Authors Suggest Major Policy Shifts to Boost Biosimilar Development, Accessibility

Cardinal Health Exec: How Adalimumab Biosimilars Can Reshape the US Health Care Industry

Podcasts

On this episode, we’re giving an overview of some of the biggest stories in the business space regarding biosimilars, like the approval of the first neurology biosimilar, growth projections from company quarterly expense reports, and some analyses about the health of the market.

Biosimilars Business Roundup For August 2023—Podcast Edition

With the exemption of female sex in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and 

, none of the candidate predictors were linked with SB5 discontinuation, according to 

Persistence on SB5 was high, treatment effectiveness was sustained, and no safety signals were identified.

Although transitioning from reference adalimumab (Humira) to SB5 had formerly been analyzed previously, the researchers said that long-term, real-world evidence in representative populations was required.

First, the non-interventional PROPER study produced real-world evidence on patient-reported outcome measures (PROM) after transition in routine practice from reference adalimumab to the EMA-approved SB5 biosimilar adalimumab (Hadlima) in patients with immune-mediated inflammatory disease (IMID).

Biologic disease-modifying anti-rheumatic drugs (DMARDS) as therapy options for patients with IMIDs has proven vital. However, accessibility to DMARDs can be limited. Biosimilars can be cost-effective alternatives that might mitigate some of those restrictions.

Adults with RA, axSpA, psoriatic arthritis (PsA), CD, or ulcerative colitis (UC) across Europe at 63 siteswere enrolled in the study. Eligible patients received at least 16 weeks of routine treatment with reference adalimumab before switching to SB5, and were monitored for 48 weeks after the transition. The primary objective was to analyze candidate predictors (clinically relevant baseline variables with incidence ≥ 15% by indication cohort) linked with persistence on SB5 at 48 weeks after initiation. Key primary outcome measures were persistence on SB5 (estimated by Kaplan-Meier methodology) and clinical characteristics and disease activity scores at the time of switch to SB5 treatment (baseline).

A total of 955 eligible patients were enrolled (RA, n = 207; axSpA, n

= 12), 932 of whom (97.65) finished follow-up and 722 (75.6%) were still taking SB5 at week 48. Kaplan–Meier predictions of persistence on SB5 at week 48 for RA, axSpA, PsA, and CD were 0.86 (0.80-0.90), 0.80 (0.71-0.86), 0.81 (0.74–0.86), and 0.72 (0.67-0.76), respectively. The single candidate predictor linked with probability of SB5 discontinuation before week 48 was female sex (RA: HR, 3.53; 95% CI, 1.07-11.67; axSpA: HR, 2.38; 95% CI, 1.11-5.14; CD: HR, 2.21; 96% CI, 1.54-3.18).

Disease activity scores stayed largely unchanged throughout the study, with proportions by cohort in remission at baseline versus week 48 being 58.2% vs 57.2%, 81.0% vs 78.0%, 94.7% vs 93.7%, and 84.0% vs 85.1% for patients with RA, axSpA, PsA, and CD, respectively. Comparably, the SB5 dosing regimen stayed unchanged for most patients from baseline to week 48, the most common regimen being 40 mg every 2 weeks.

Notably, only female sex was linked with increased risk for SB5 discontinuation in the RA, axSpA, and CD cohorts of the candidate estimates of persistence. These findings were comparable with previous data.

“Most patients in each cohort were in remission or had stable disease at transition, and showed no meaningful differences in disease activity measures over time post-transition (3–12 month follow-up),” said the study authors.

In terms of safety, no new safety signals were identified in this study, and AEs were generally consistent with those previously reported in patients with rheumatic or gastroenterologic IMIDs treated with SB5.

Of note, the possible impact of a “nocebo effect” should also be considered. Efforts to mitigate this, like communication and training, may help informed decision-making in patients who are considering switching from a reference drug to a biosimilar.

Additionally, the researchers said that special consideration should be given to female patients who are considering switching, since they seem to be more vulnerable to discontinuation than their male counterparts.

“There were no meaningful differences in disease activity or PROM scores between baseline and week 48 post-transition (most patients in each cohort remained in remission or had stable disease), and no new safety signals were observed. These findings suggest that in the context of treatment persistence and within the baseline categories observed, there was no evidence to mitigate against transition,” concluded the researchers.

Müller-Ladner U, Dignass A, Gaffney K, et al. The PROPER study: A 48-week, pan-european, real-world study of biosimilar SB5 following transition from reference adalimumab in patients with immune-mediated inflammatory disease. 

. Published online August 26, 2023. doi:10.1007/s40259-023-00616-3

Switching from reference to biosimilar adalimumab was found to be safe and effective. Researchers cautioned that female patients may be at higher risk of discontinuation compared with their male counterparts.

Higher Risk of Discontinuation During Biosimilar Switching Found Among Women

Here are the top 5 biosimilar articles for the week of August 28th, 2023.

Number 5: Stelara (ustekinumab) and Enbrel (etanercept), 2 originator medications that 

 within the next decade, were among the 10 preliminary drugs chosen for Medicare price negotiation under the Inflation Reduction Act (IRA).

Number 4: A meta-analysis and systematic review of data on over 10,000 patients with rheumatoid arthritis (RA) found that etanercept, adalimumab, and infliximab 

Number 3: Dan Danielson, RPh, MS, senior director, market access solutions, at PrecisionValue, a market access marketing firm, explained 

 at play slowing down biosimilar uptake in the United States.

Number 2: Fran Gregory, PharmD, MBA, vice president of emerging therapies at Cardinal Health, published her opinions on the 

future of biosimilars in the United States

, foreshadowing immense growth and a transformation of the US health care industry thanks to biosimilars.

 indicated for multiple sclerosis (MS), Sandoz’ Tyruko (natalizumab-sztn), a biosimilar referencing Tysabi (natalizumab).

Here are the top 5 biosimilar articles for the week of August 28, 2023.

The Top 5 Biosimilar Articles for the Week of August 28

The practice of single switching between approved biologics and biosimilars of tumor necrosis factor inhibitors (TNFis) is effective and safe for 

Researchers aimed to evaluate the impact of switching on the treatment of rheumatoid arthritis through a network of evidence of head to head comparisons of switching and nonswitching arms of TNFi biologics and biosimilars.

A systematic review and network meta-analysis were undertaken to compare switching and nonswitching groups of treatments.

The use of TNFi biosimilars for patients using disease-modifying antirheumatic drugs has been the standard of care for rheumatoid arthritis in areas around the globe where biosimilars are accessible. In circumstances where a patient will have their treatment exchanged or replaced by another treatment, the decision about switching should be based on the top level of evidence available.

First, pooled risk relative (RR) or standardized mean differences (SMD) with 95% credible intervals (95% CrIs) were collected. A total of 17 randomized trials with a switching phase involving 6,562 patients were included.

Results demonstrated that just 1 switch from biologics to biosimilars compared to continuing biologics had comparable effects for primary and co-primary outcomes, the American College of Rheumatology criteria with 20% response (ACR20; 7 trials; n = 1,926 patients; RR, 0.98; 95% CrIs, 0.93-1.03) and the Health Assessment Questionnaire–Disability Index (HAQ-DI; 5 trials; n = 1,609 patients; SMD, –0.07; 95% CrIs, –0.23 to 0.1), and within the equivalence margins of ACR20 (RR, 0.94, 1.06) and HAQ-DI (SMD, –0.22 to 0.22). The possibility of treatment-emergent adverse events, discontinuation, and positive anti-drug antibodies were comparable after switching.

Safety results weren’t precise, and the follow-up period might not be adequate to review long-term effects, especially malignancies.

Then, in terms of safety, the evidence displayed that the risk for both outcomes was similar within and between switching and nonswitching arms. The 95% CrIs for the risk for serious treatment emergent adverse events (TEAEs), hypersensitivity, infusion-related reactions, malignancies, and serious infections crossed the null effect but weren’t precise (small number of events and high heterogeneity between trials). The researchers weren’t able to perform network metal analysis (NMA) for ISRs, active tuberculosis, and mortality because of rare event rates (n < 30).

The clinical response or functional capacity of patients following switching was equal within and between switching and nonswitching groups, and all comparisons met previously stated margins of equivalence. Additionally, there is evidence of a similar risk of experiencing TEAE or stopping study rates (i.e., comparable safety and tolerability were seen after switching). Since the rare rates of some adverse events, the researchers aren’t sure about the effects of switching in these cases. The immune response was comparable for patients in the switching and nonswitching treatment arms.

Even though the researchers extended the finding that these trials were at high risk of bias, new studies should try to incorporate vital aspects of quality and reporting when evaluating the impact of switching between treatments.

Importantly, their evidence does not focus on the issue of switching from a biosimilar to another biosimilar of the same reference biologic drugs or multiple switches. These questions persist and should be the concern of future research.

To the best of the researchers’ knowledge, this study is the most comprehensive systematic review and NMA within a Bayesian framework to review the impact of switching between biosimilars of adalimumab, etanercept, and infliximab and its reference biologics drugs on rheumatoid arthritis treatment.

Some limitations were present in this study. First, multiple comparisons such as arm switching (biosimilar to reference product) comprised of only 1 or a few studies, constricting the confidence of estimates. Secondly, special attention should be paid to the interpretation of some safety and immunogenicity outcomes, that indicated the null effect between switching and nonswitching arms.

Even though safety results were imprecise, and the follow-up period may not be sufficiently long enough, especially regarding malignancies, “these findings support the rational practice of switching reference biologics and biosimilar drugs of adalimumab, etanercept, and infliximab for patients with rheumatoid arthritis,” concluded the study authors.

de Oliveira Ascef B, Almeida MO, de Medeiros-Ribeiro AC, de Oliveira Andrade DC, de Oliveira Junior HA, de Soárez PC. Impact of switching between reference biologics and biosimilars of tumour necrosis factor inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis. 

. Published online August 22, 2023. doi:10.1038/s41598-023-40222-5

Single switching between approved biologics and biosimilars of tumor necrosis factor inhibitors (TNFis) were found to be safe and effective for rheumatoid arthritis.