PARIS, France—Golimumab, a new TNF-inhibitor given subcutaneously once a month, is effective in rheumatoid arthritis (RA) in patients previously treated with anti-TNF-α therapy, in RA that is resistant to other TNF-inhibitors and to methotrexate (MTX), and in RA that is treatment-naïve. Researchers reported their findings at the 2008 European League Against Rheumatism (EULAR) Annual Congress of Rheumatology.^1-3

"Our findings show that golimumab holds great promise in various RA patient populations, including those patients who have previously discontinued other TNF inhibitors," said lead study investigator Josef S. Smolen, MD, professor and chairman with the department of rheumatology at Medical University of Vienna. "Golimumab may provide an appropriate treatment option to the many people facing the consequences of this debilitating disease."

GO AFTER study shows golimumab success after other TNF-inhibitor failure

Dr. Smolen reported data for 461 patients with moderate-to-severe active RA who had been previously treated with anti-TNFα agents and who were randomized to placebo (n = 155), to golimumab 50 mg (n = 153), or to golimumab 100 mg (n = 153). The primary endpoint was the proportion of patients who achieved ACR20 response at week 14. Secondary endpoints included improvement from baseline to week 24 in health assessment questionnaire (HAQ) quality of life scores. HAQ assess the degree of difficulty a patient has in accomplishing tasks in eight functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and other activities of daily living).

The GO-AFTER (GOlimumab After Former anti-TNF Therapy Evaluated in RA ) trial included patients with active RA of 8.65 years mean duration who had previously received at least one anti-TNFα: 25% (n = 115) had received two therapies and 9% (n = 43) had received three. Fully 58% had discontinued previous TNF inhibitors due to lack of efficacy and 17% had discontinued due to side effects. At baseline, 66% of patients received MTX; 5% and 7% received sulfasalazine (SSZ) and hydroxychloroquine (HCQ), respectively. Patients continued stable doses of MTX, SSZ, and/or HCQ if they had received them at baseline.

Patients in both golimumab groups experienced significant improvements in signs and symptoms and physical function at week 14 [Table 1]. Dr. Smolen reported that the improvements in disease activity and physical function were sustained for at least 6 months. Patients who received golimumab 50 mg and 100 mg (35% and 38%, respectively) achieved the primary endpoint of ACR 20 at week 14 compared with 18% of placebo patients (P <.001).

Among the 58%of patients whose prior anti-TNFα therapy had been discontinued due to lack of efficacy, 36% on 50 mg (P = .006) and 43% on 100 mg (P <.001) achieved ACR20 compared with 18% on placebo.

"When treating patients with progressive rheumatoid arthritis, our goal is to reduce pain and improve physical function," said co-investigator Jonathan Kay, MD, who is director of clinical trials, rheumatology unit at Massachusetts General Hospital and is associate clinical professor of medicine at Harvard Medical School. "We are encouraged by the results of these trials which suggest that golimumab may offer a significant benefit to a growing population of RA patients with prior TNF-inhibitor experience."

Through 24 weeks, 72%, 66%, and 78% of patients in the placebo, golimumab 50 mg and 100 mg groups, respectively, experienced at least one adverse event (AE). Ten percent of patients in the placebo group experienced serious AEs compared with 7% and 5% of patients in the 50 mg and 100 mg groups, respectively. Serious infections were reported in 3%, 3%, and 1% of patients; injection site reactions (ISR) through week 16 occurred in 3%, 4%, and 11% of patients in the placebo, golimumab 50 mg and 100 mg groups, respectively. The most commonly reported ISR was erythema, none were serious or severe or led to study withdrawal. Antibodies to golimumab were detected in 4% of both golimumab arms.

The researchers concluded that golimumab significantly reduced RA signs and symptoms, improved physical function, and was generally well-tolerated.

GO-FORWARD study shows golimumab efficacy as first TNF inhibitor after MTX

In the GOlimumab FOR subjects With Active RA Despite MTX (GO-FORWARD) study, both golimumab 50 mg and 100 mg doses were studied in patients whose disease was active despite ongoing treatment with MTX. At week 14, 55% of patients who received golimumab 50 mg plus MTX and 56% who received golimumab 100 mg plus MTX achieved ACR20 compared with 33% on placebo and MTX (P <0.01 and P <.001, respectively). Improvements were seen as early as first clinical assessment at 4 weeks after the first golimumab injection, and generally continued to improve over time.

"The data in this study demonstrate that golimumab is beneficial in improving numerous disease parameters, including inducing remission, in patients whose disease was active despite ongoing treatment with methotrexate," said lead study investigator Edward Keystone, MD, FRCPC, director of the Rebecca MacDonald Centre for arthritis an autoimmune disease at Mount Sinai Hospital in Toronto. "Since some patients do not respond adequately to MTX alone, this combination therapy could prove to be a highly valuable treatment option based on these results."

Golimumab patients also experienced improvement in HAQ: at 24 weeks, 68% of patients in the 50 mg dosing group and 72% in the 100 mg group experienced clinically relevant improvement in physical function, compared with 39% in the placebo plus MTX group (P <.0001).

GO-BEFORE study tries up-front golimumab, misses primary endpoint

In another phase III study, GOlimumab Before Employing methotrexate as the First-line Option in the treatment of Rheumatoid arthritis of Early onset (GO-BEFORE), MTX-naïve patients treated with 50 mg or 100 mg plus MTX experienced improvement in RA signs and symptoms and in disease activity.³ However, the study missed the primary endpoint (ACR50 by ITT) analysis. The endpoint was met only when three patients who had not received their assigned golimumab were excluded from the analysis. Patients who received 50 mg plus MTX had significantly greater improvement in RA signs and symptoms through week 24.

In the primary analysis of the combined golimumab plus MTX groups, 38% (40% on 50 mg and 37% on 100 mg) achieved at least ACR50 response through week 24 compared with 29% on placebo plus MTX (P = .053 for the combined group, P = .042 for 50 mg, and P = .177 for 100 mg). Additionally, 62% in the combined golimumab plus MTX group (62% for each dose group) achieved ACR20 compared with 49% in the placebo group (P = .011 for the combined group and P = .028 for each dose group).

"These data show that treatment with golimumab induces an important depth of response, improving multiple aspects of RA and leading to significant decreases in disease activity," said lead investigator Roy Fleischmann, MD, clinical professor, department of internal medicine at the University of Texas Southwestern Medical Center and chief, division of rheumatology at St. Paul University Hospital in Dallas, Texas. "Golimumab…is a promising treatment option for multiple patient populations with this chronic and potentially debilitating inflammatory disease."

Assessment	Placebo n=155	GLM 50 mg n=153	GLM 100 mg n=153	GLM 50 mg and 100 mg combined
Week 14
ACR20 (%)	28 (18.1)	54 (35.3)*	58 (37.9)*	112 (36.6)*
Week 24
ACR20 (%)	26 (16.8)	52 (34.0)*	67 (43.8)*	119 (38.9)*
HAQ (improvement ≥0.25 from baseline) (%)	53 (34.2)	77 (50.3)**	82 (53.6)*	159 (51.9)*

*P <.001, ** P <.01;+DAS28 responders = EULAR Moderate-Good

Source: Adapted from EULAR 2008.¹

References

1. Smolen J, Kay J, Doyle MK, et al. Golimumab, a new human anti-TNF-alpha monoclonal antibody, subcutaneously administered every 4 weeks in patients with active rheumatoid arthritis who were previously treated with anti-TNF-alpha agent(s): results of the randomized, double-blind, placebo-controlled GO-BEFORE study. Presented at: EULAR 2008; June 11-14, 2008; Paris, France. Presentation OP-0010.
2. Keystone E, Genovese MC, Klareskog L. Golimumab, a new human anti-TNF-alpha monoclonal antibody, administered subcutaneously every 4 weeks in patients with active rheumatoid arthritis despite methotrexate: week 24 results of the randomized, double-blind, placebo-controlled, GO-FORWARD study. Presented at: EULAR 2008; June 11-14, 2008; Paris, France. Presentation THU0156.
3. Emery P, Fleischmann RM, Moreland LW, et al. Golimumab (GLM), a new human anti-TNF-alpha monoclonal antibody, administered subcutaneously (sc) every 4 weeks in methotrexate-naïve patients with active rheumatoid arthritis (RA): a randomized, double-blind, placebo-controlled, GO-BEFORE study. Presented at: EULAR 2008; June 11-14, 2008; Paris, France. Presentation THU-0138.